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Patients find CAC more persuasive than ASCVD risk score for statin decisions
Patients who received a protocol-driven recommendation to initiate statin therapy for primary prevention of cardiovascular disease based upon their CT angiography coronary artery calcium score were twice as likely to actually start on the drug than those whose recommendation was guided by the American College of Cardiology/American Heart Association Pooled Cohort Equations Risk Calculator, according to the results of the randomized CorCal Vanguard study.
These results suggest that patients – and their primary care physicians – find the conventional method of screening for cardiovascular risk using the Pooled Cohort Equations to estimate the 10-year risk of MI or stroke, as recommended in ACC/AHA guidelines, to be less persuasive than screening for the presence or absence of actual disease as captured by CT angiography images and the associated coronary artery calcium (CAC) score, Joseph B. Muhlestein, MD, said at the joint scientific sessions of the ACC and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.
The CorCal Vanguard study included 601 patients with an average baseline LDL cholesterol of 120 mg/dL, an average age of 60 years, and no history of cardiovascular disease, diabetes, or prior statin therapy. They were randomized to decision-making regarding statin therapy based on either the ACC/AHA guideline–endorsed Pooled Cohort Equations, which use an estimated 10-year risk of 7.5% or more as the threshold for statin initiation, or their CAC score.
If a patient’s CAC score was 0, the recommendation was against starting a statin. Everyone with a CAC greater than 100 received a recommendation for high-intensity statin therapy. And for those with a CAC of 1-100, the decision defaulted to the results of the Pooled Cohort Equations. The screening results were provided to a patient’s primary physician so they could engage in joint decision-making regarding initiation of statin therapy. Adherence to a screening-based recommendation to start on a statin was assessed at 3 and 12 months of follow-up, explained Dr. Muhlestein, a cardiologist at the Intermountain Medical Center Heart Institute in Salt Lake City.
He noted that CorCal Vanguard was merely a feasibility study. Based on the study results he presented at ACC 2020, the full 9,000-patient CorCal primary prevention trial is now enrolling participants. CorCal is the first randomized trial to pit the Pooled Cohort Equations against the CAC score in a large study looking for differences in downstream clinical outcomes.
The rationale for this line of clinical research lies in the known limitations of the ACC/AHA risk calculator. “It may overestimate risk in some populations, patients aren’t always adherent to Pooled Cohort Equations Risk Calculator recommendations, and it doesn’t include novel risk markers such as C-reactive protein that some consider important for risk assessment. And the big question: Should we continue risk screening to determine potential benefit from drug therapy, or should we switch to disease screening?” the cardiologist commented.
The CorCal Vanguard results
A recommendation to start statin therapy was made in 48% of patients in the Pooled Cohort Equations group, versus 36% of the group randomized to CAC. However, only 17% of patients in the Pooled Cohort Equations group actually initiated a statin, a significantly lower rate than the 26% figure in the CAC arm. Fully 70% of patients who received a recommendation to start taking a statin on the basis of their CAC score actually did so, compared to just 36% of those whose recommendation was based upon their Pooled Cohort Equations Risk Calculator.
At 3 months of follow-up, 61% of patients who received an initial recommendation to start statin therapy based upon their CAC screening were actually taking a statin, compared with 41% of those whose recommendation was based upon the Pooled Cohort Equations. At 12 months, the figures were 64% and 49%.
In both groups, at 12 months of follow-up, the No. 1 reason patients weren’t taking a statin as recommended was that their personal physician had advised against it or never prescribed it. That accounted for roughly half of the nonadherence. Another quarter was because of a preference to try lifestyle change first. Fear of drug side effects was a less common reason.
Putting the CorCal Vanguard study results in perspective, Dr. Muhlestein observed that, prior to the screening study, none of the participants had ever been on a statin, yet 37% of them were found by one screening method or the other to be at high cardiovascular risk. Of those high-risk patients, 51% actually initiated statin therapy and the majority of them were still taking their medication 12 months later.
“That has to be a good thing. It emphasizes what can be done when proactive primary prevention is practiced,” the cardiologist said.
He reported having no financial conflicts regarding the CorCal study, which was funded by a grant from the Dell Loy Hansen Cardiovascular Research Fund.
SOURCE: Muhlestein JB et al. ACC 2020, Abstract 909-12.
Patients who received a protocol-driven recommendation to initiate statin therapy for primary prevention of cardiovascular disease based upon their CT angiography coronary artery calcium score were twice as likely to actually start on the drug than those whose recommendation was guided by the American College of Cardiology/American Heart Association Pooled Cohort Equations Risk Calculator, according to the results of the randomized CorCal Vanguard study.
These results suggest that patients – and their primary care physicians – find the conventional method of screening for cardiovascular risk using the Pooled Cohort Equations to estimate the 10-year risk of MI or stroke, as recommended in ACC/AHA guidelines, to be less persuasive than screening for the presence or absence of actual disease as captured by CT angiography images and the associated coronary artery calcium (CAC) score, Joseph B. Muhlestein, MD, said at the joint scientific sessions of the ACC and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.
The CorCal Vanguard study included 601 patients with an average baseline LDL cholesterol of 120 mg/dL, an average age of 60 years, and no history of cardiovascular disease, diabetes, or prior statin therapy. They were randomized to decision-making regarding statin therapy based on either the ACC/AHA guideline–endorsed Pooled Cohort Equations, which use an estimated 10-year risk of 7.5% or more as the threshold for statin initiation, or their CAC score.
If a patient’s CAC score was 0, the recommendation was against starting a statin. Everyone with a CAC greater than 100 received a recommendation for high-intensity statin therapy. And for those with a CAC of 1-100, the decision defaulted to the results of the Pooled Cohort Equations. The screening results were provided to a patient’s primary physician so they could engage in joint decision-making regarding initiation of statin therapy. Adherence to a screening-based recommendation to start on a statin was assessed at 3 and 12 months of follow-up, explained Dr. Muhlestein, a cardiologist at the Intermountain Medical Center Heart Institute in Salt Lake City.
He noted that CorCal Vanguard was merely a feasibility study. Based on the study results he presented at ACC 2020, the full 9,000-patient CorCal primary prevention trial is now enrolling participants. CorCal is the first randomized trial to pit the Pooled Cohort Equations against the CAC score in a large study looking for differences in downstream clinical outcomes.
The rationale for this line of clinical research lies in the known limitations of the ACC/AHA risk calculator. “It may overestimate risk in some populations, patients aren’t always adherent to Pooled Cohort Equations Risk Calculator recommendations, and it doesn’t include novel risk markers such as C-reactive protein that some consider important for risk assessment. And the big question: Should we continue risk screening to determine potential benefit from drug therapy, or should we switch to disease screening?” the cardiologist commented.
The CorCal Vanguard results
A recommendation to start statin therapy was made in 48% of patients in the Pooled Cohort Equations group, versus 36% of the group randomized to CAC. However, only 17% of patients in the Pooled Cohort Equations group actually initiated a statin, a significantly lower rate than the 26% figure in the CAC arm. Fully 70% of patients who received a recommendation to start taking a statin on the basis of their CAC score actually did so, compared to just 36% of those whose recommendation was based upon their Pooled Cohort Equations Risk Calculator.
At 3 months of follow-up, 61% of patients who received an initial recommendation to start statin therapy based upon their CAC screening were actually taking a statin, compared with 41% of those whose recommendation was based upon the Pooled Cohort Equations. At 12 months, the figures were 64% and 49%.
In both groups, at 12 months of follow-up, the No. 1 reason patients weren’t taking a statin as recommended was that their personal physician had advised against it or never prescribed it. That accounted for roughly half of the nonadherence. Another quarter was because of a preference to try lifestyle change first. Fear of drug side effects was a less common reason.
Putting the CorCal Vanguard study results in perspective, Dr. Muhlestein observed that, prior to the screening study, none of the participants had ever been on a statin, yet 37% of them were found by one screening method or the other to be at high cardiovascular risk. Of those high-risk patients, 51% actually initiated statin therapy and the majority of them were still taking their medication 12 months later.
“That has to be a good thing. It emphasizes what can be done when proactive primary prevention is practiced,” the cardiologist said.
He reported having no financial conflicts regarding the CorCal study, which was funded by a grant from the Dell Loy Hansen Cardiovascular Research Fund.
SOURCE: Muhlestein JB et al. ACC 2020, Abstract 909-12.
Patients who received a protocol-driven recommendation to initiate statin therapy for primary prevention of cardiovascular disease based upon their CT angiography coronary artery calcium score were twice as likely to actually start on the drug than those whose recommendation was guided by the American College of Cardiology/American Heart Association Pooled Cohort Equations Risk Calculator, according to the results of the randomized CorCal Vanguard study.
These results suggest that patients – and their primary care physicians – find the conventional method of screening for cardiovascular risk using the Pooled Cohort Equations to estimate the 10-year risk of MI or stroke, as recommended in ACC/AHA guidelines, to be less persuasive than screening for the presence or absence of actual disease as captured by CT angiography images and the associated coronary artery calcium (CAC) score, Joseph B. Muhlestein, MD, said at the joint scientific sessions of the ACC and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.
The CorCal Vanguard study included 601 patients with an average baseline LDL cholesterol of 120 mg/dL, an average age of 60 years, and no history of cardiovascular disease, diabetes, or prior statin therapy. They were randomized to decision-making regarding statin therapy based on either the ACC/AHA guideline–endorsed Pooled Cohort Equations, which use an estimated 10-year risk of 7.5% or more as the threshold for statin initiation, or their CAC score.
If a patient’s CAC score was 0, the recommendation was against starting a statin. Everyone with a CAC greater than 100 received a recommendation for high-intensity statin therapy. And for those with a CAC of 1-100, the decision defaulted to the results of the Pooled Cohort Equations. The screening results were provided to a patient’s primary physician so they could engage in joint decision-making regarding initiation of statin therapy. Adherence to a screening-based recommendation to start on a statin was assessed at 3 and 12 months of follow-up, explained Dr. Muhlestein, a cardiologist at the Intermountain Medical Center Heart Institute in Salt Lake City.
He noted that CorCal Vanguard was merely a feasibility study. Based on the study results he presented at ACC 2020, the full 9,000-patient CorCal primary prevention trial is now enrolling participants. CorCal is the first randomized trial to pit the Pooled Cohort Equations against the CAC score in a large study looking for differences in downstream clinical outcomes.
The rationale for this line of clinical research lies in the known limitations of the ACC/AHA risk calculator. “It may overestimate risk in some populations, patients aren’t always adherent to Pooled Cohort Equations Risk Calculator recommendations, and it doesn’t include novel risk markers such as C-reactive protein that some consider important for risk assessment. And the big question: Should we continue risk screening to determine potential benefit from drug therapy, or should we switch to disease screening?” the cardiologist commented.
The CorCal Vanguard results
A recommendation to start statin therapy was made in 48% of patients in the Pooled Cohort Equations group, versus 36% of the group randomized to CAC. However, only 17% of patients in the Pooled Cohort Equations group actually initiated a statin, a significantly lower rate than the 26% figure in the CAC arm. Fully 70% of patients who received a recommendation to start taking a statin on the basis of their CAC score actually did so, compared to just 36% of those whose recommendation was based upon their Pooled Cohort Equations Risk Calculator.
At 3 months of follow-up, 61% of patients who received an initial recommendation to start statin therapy based upon their CAC screening were actually taking a statin, compared with 41% of those whose recommendation was based upon the Pooled Cohort Equations. At 12 months, the figures were 64% and 49%.
In both groups, at 12 months of follow-up, the No. 1 reason patients weren’t taking a statin as recommended was that their personal physician had advised against it or never prescribed it. That accounted for roughly half of the nonadherence. Another quarter was because of a preference to try lifestyle change first. Fear of drug side effects was a less common reason.
Putting the CorCal Vanguard study results in perspective, Dr. Muhlestein observed that, prior to the screening study, none of the participants had ever been on a statin, yet 37% of them were found by one screening method or the other to be at high cardiovascular risk. Of those high-risk patients, 51% actually initiated statin therapy and the majority of them were still taking their medication 12 months later.
“That has to be a good thing. It emphasizes what can be done when proactive primary prevention is practiced,” the cardiologist said.
He reported having no financial conflicts regarding the CorCal study, which was funded by a grant from the Dell Loy Hansen Cardiovascular Research Fund.
SOURCE: Muhlestein JB et al. ACC 2020, Abstract 909-12.
FROM ACC 2020
More from REDUCE-IT: Icosapent ethyl cuts revascularization by a third
A new analysis from the REDUCE-IT trial has shown that the high-strength eicosapentaenoic acid product icosapent ethyl (Vascepa; Amarin) reduced the number of revascularization procedures by more than one-third in statin-treated patients whose triglyceride levels were elevated and who were at increased cardiovascular risk.
The new data were presented at the Society for Cardiovascular Angiography & Interventions virtual annual scientific sessions.
REDUCE-IT, a multicenter, double-blind, placebo-controlled trial, randomly assigned statin-treated patients whose triglyceride levels were elevated (135-499 mg/dL), whose LDL cholesterol levels were controlled (41-100 mg/dL), and who had established cardiovascular disease or diabetes plus risk factors to receive either icosapent ethyl 4 g daily or placebo.
The primary composite and other cardiovascular endpoints were substantially reduced. Prespecified analyses examined all coronary revascularizations, recurrent revascularizations, and revascularization subtypes.
“Compared with placebo, icosapent ethyl 4 g/day significantly reduced first and total revascularization events by 34% and 36%, respectively,” REDUCE-IT investigator Benjamin Peterson, MD, of Brigham and Women’s Hospital, Boston, concluded during his presentation.
This reduction was consistent with respect to urgent, emergent, and elective revascularization procedures overall, as well as percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) individually, he reported.
“Prior therapies aimed at patients with elevated triglycerides have not demonstrated a consistent benefit in reducing coronary revascularization, and to the best of our knowledge, this is the first non–LDL cholesterol intervention in a major randomized trial in which statin-treated patients underwent fewer CABG surgeries,” Dr. Peterson stated.
“These data highlight the substantial impact of icosapent ethyl on the underlying atherothrombotic burden in the at-risk REDUCE-IT population,” he added.
Detailed results showed that the percentage of patients who underwent first revascularizations was 9.2% with icosapent ethyl versus 13.3% with placebo (hazard ratio, 0.66; P < .0001; number needed to treat, 25).
Similar reductions were observed in total (first and subsequent) revascularizations (risk ratio, 0.64; P < .0001) and across urgent, emergent, and elective revascularizations. Icosapent ethyl significantly reduced the need for PCI (HR, 0.68; P < .0001) and CABG (HR, 0.61; P = .0005).
The moderator of a SCAI press conference, Kirk Garratt, MD, of the Center for Heart and Vascular Health at Christiana Care Health System in Wilmington, Del., said that “this is an impressive impact. I couldn’t count the number of zeros in the P value.”
Timothy Henry, MD, of Christ Hospital in Cincinnati, said that REDUCE-IT was an important trial. “It showed a very impressive effect on revascularizations along with all the other benefits.” But he suggested that the uptake in usage of icosapent ethyl in the United States has been slow, and he asked what could be done to enhance this.
REDUCE-IT senior investigator Deepak Bhatt, MD, replied that the product was only approved for the REDUCE-IT indication in December 2019, and he suggested that initial uptake may have been affected by the current COVID-19 pandemic.
“This new REDUCE-IT indication ― patients with established cardiovascular disease or diabetes plus risk factors who have moderately elevated triglycerides and controlled LDL ― includes a lot of patients, between 15% and 50% of all cardiovascular patients,” he said.
“We wanted to present this revascularization data at the SCAI meeting, as it is superimportant that interventional cardiologists know about this. Interventionalists have now taken ownership of LDL and make sure patients are on statins, and we hope they will now do the same thing for triglycerides,” Dr. Bhatt commented.
Dr. Henry agreed. “It should be a simple thing to take all secondary prevention patients with eligible triglycerides and be aggressive with this new therapy.”
Dr. Bhatt noted that a cost-effectiveness analysis of the REDUCE-IT trial that was presented at last year’s American Heart Association meeting “has shown the drug to be highly cost effective and actually cost saving at the current list price.”
Asked what the mechanism of benefit is, Dr. Bhatt said that “there has been good basic science showing that EPA [eicosapentaenoic acid] stabilizes cell membranes and reduces plaque vulnerability and progression.”
REDUCE-IT was sponsored by Amarin. Brigham and Women’s Hospital receives research funding from Amarin for Dr. Bhatt’s role as chair of the trial.
A version of this article originally appeared on Medscape.com.
A new analysis from the REDUCE-IT trial has shown that the high-strength eicosapentaenoic acid product icosapent ethyl (Vascepa; Amarin) reduced the number of revascularization procedures by more than one-third in statin-treated patients whose triglyceride levels were elevated and who were at increased cardiovascular risk.
The new data were presented at the Society for Cardiovascular Angiography & Interventions virtual annual scientific sessions.
REDUCE-IT, a multicenter, double-blind, placebo-controlled trial, randomly assigned statin-treated patients whose triglyceride levels were elevated (135-499 mg/dL), whose LDL cholesterol levels were controlled (41-100 mg/dL), and who had established cardiovascular disease or diabetes plus risk factors to receive either icosapent ethyl 4 g daily or placebo.
The primary composite and other cardiovascular endpoints were substantially reduced. Prespecified analyses examined all coronary revascularizations, recurrent revascularizations, and revascularization subtypes.
“Compared with placebo, icosapent ethyl 4 g/day significantly reduced first and total revascularization events by 34% and 36%, respectively,” REDUCE-IT investigator Benjamin Peterson, MD, of Brigham and Women’s Hospital, Boston, concluded during his presentation.
This reduction was consistent with respect to urgent, emergent, and elective revascularization procedures overall, as well as percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) individually, he reported.
“Prior therapies aimed at patients with elevated triglycerides have not demonstrated a consistent benefit in reducing coronary revascularization, and to the best of our knowledge, this is the first non–LDL cholesterol intervention in a major randomized trial in which statin-treated patients underwent fewer CABG surgeries,” Dr. Peterson stated.
“These data highlight the substantial impact of icosapent ethyl on the underlying atherothrombotic burden in the at-risk REDUCE-IT population,” he added.
Detailed results showed that the percentage of patients who underwent first revascularizations was 9.2% with icosapent ethyl versus 13.3% with placebo (hazard ratio, 0.66; P < .0001; number needed to treat, 25).
Similar reductions were observed in total (first and subsequent) revascularizations (risk ratio, 0.64; P < .0001) and across urgent, emergent, and elective revascularizations. Icosapent ethyl significantly reduced the need for PCI (HR, 0.68; P < .0001) and CABG (HR, 0.61; P = .0005).
The moderator of a SCAI press conference, Kirk Garratt, MD, of the Center for Heart and Vascular Health at Christiana Care Health System in Wilmington, Del., said that “this is an impressive impact. I couldn’t count the number of zeros in the P value.”
Timothy Henry, MD, of Christ Hospital in Cincinnati, said that REDUCE-IT was an important trial. “It showed a very impressive effect on revascularizations along with all the other benefits.” But he suggested that the uptake in usage of icosapent ethyl in the United States has been slow, and he asked what could be done to enhance this.
REDUCE-IT senior investigator Deepak Bhatt, MD, replied that the product was only approved for the REDUCE-IT indication in December 2019, and he suggested that initial uptake may have been affected by the current COVID-19 pandemic.
“This new REDUCE-IT indication ― patients with established cardiovascular disease or diabetes plus risk factors who have moderately elevated triglycerides and controlled LDL ― includes a lot of patients, between 15% and 50% of all cardiovascular patients,” he said.
“We wanted to present this revascularization data at the SCAI meeting, as it is superimportant that interventional cardiologists know about this. Interventionalists have now taken ownership of LDL and make sure patients are on statins, and we hope they will now do the same thing for triglycerides,” Dr. Bhatt commented.
Dr. Henry agreed. “It should be a simple thing to take all secondary prevention patients with eligible triglycerides and be aggressive with this new therapy.”
Dr. Bhatt noted that a cost-effectiveness analysis of the REDUCE-IT trial that was presented at last year’s American Heart Association meeting “has shown the drug to be highly cost effective and actually cost saving at the current list price.”
Asked what the mechanism of benefit is, Dr. Bhatt said that “there has been good basic science showing that EPA [eicosapentaenoic acid] stabilizes cell membranes and reduces plaque vulnerability and progression.”
REDUCE-IT was sponsored by Amarin. Brigham and Women’s Hospital receives research funding from Amarin for Dr. Bhatt’s role as chair of the trial.
A version of this article originally appeared on Medscape.com.
A new analysis from the REDUCE-IT trial has shown that the high-strength eicosapentaenoic acid product icosapent ethyl (Vascepa; Amarin) reduced the number of revascularization procedures by more than one-third in statin-treated patients whose triglyceride levels were elevated and who were at increased cardiovascular risk.
The new data were presented at the Society for Cardiovascular Angiography & Interventions virtual annual scientific sessions.
REDUCE-IT, a multicenter, double-blind, placebo-controlled trial, randomly assigned statin-treated patients whose triglyceride levels were elevated (135-499 mg/dL), whose LDL cholesterol levels were controlled (41-100 mg/dL), and who had established cardiovascular disease or diabetes plus risk factors to receive either icosapent ethyl 4 g daily or placebo.
The primary composite and other cardiovascular endpoints were substantially reduced. Prespecified analyses examined all coronary revascularizations, recurrent revascularizations, and revascularization subtypes.
“Compared with placebo, icosapent ethyl 4 g/day significantly reduced first and total revascularization events by 34% and 36%, respectively,” REDUCE-IT investigator Benjamin Peterson, MD, of Brigham and Women’s Hospital, Boston, concluded during his presentation.
This reduction was consistent with respect to urgent, emergent, and elective revascularization procedures overall, as well as percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) individually, he reported.
“Prior therapies aimed at patients with elevated triglycerides have not demonstrated a consistent benefit in reducing coronary revascularization, and to the best of our knowledge, this is the first non–LDL cholesterol intervention in a major randomized trial in which statin-treated patients underwent fewer CABG surgeries,” Dr. Peterson stated.
“These data highlight the substantial impact of icosapent ethyl on the underlying atherothrombotic burden in the at-risk REDUCE-IT population,” he added.
Detailed results showed that the percentage of patients who underwent first revascularizations was 9.2% with icosapent ethyl versus 13.3% with placebo (hazard ratio, 0.66; P < .0001; number needed to treat, 25).
Similar reductions were observed in total (first and subsequent) revascularizations (risk ratio, 0.64; P < .0001) and across urgent, emergent, and elective revascularizations. Icosapent ethyl significantly reduced the need for PCI (HR, 0.68; P < .0001) and CABG (HR, 0.61; P = .0005).
The moderator of a SCAI press conference, Kirk Garratt, MD, of the Center for Heart and Vascular Health at Christiana Care Health System in Wilmington, Del., said that “this is an impressive impact. I couldn’t count the number of zeros in the P value.”
Timothy Henry, MD, of Christ Hospital in Cincinnati, said that REDUCE-IT was an important trial. “It showed a very impressive effect on revascularizations along with all the other benefits.” But he suggested that the uptake in usage of icosapent ethyl in the United States has been slow, and he asked what could be done to enhance this.
REDUCE-IT senior investigator Deepak Bhatt, MD, replied that the product was only approved for the REDUCE-IT indication in December 2019, and he suggested that initial uptake may have been affected by the current COVID-19 pandemic.
“This new REDUCE-IT indication ― patients with established cardiovascular disease or diabetes plus risk factors who have moderately elevated triglycerides and controlled LDL ― includes a lot of patients, between 15% and 50% of all cardiovascular patients,” he said.
“We wanted to present this revascularization data at the SCAI meeting, as it is superimportant that interventional cardiologists know about this. Interventionalists have now taken ownership of LDL and make sure patients are on statins, and we hope they will now do the same thing for triglycerides,” Dr. Bhatt commented.
Dr. Henry agreed. “It should be a simple thing to take all secondary prevention patients with eligible triglycerides and be aggressive with this new therapy.”
Dr. Bhatt noted that a cost-effectiveness analysis of the REDUCE-IT trial that was presented at last year’s American Heart Association meeting “has shown the drug to be highly cost effective and actually cost saving at the current list price.”
Asked what the mechanism of benefit is, Dr. Bhatt said that “there has been good basic science showing that EPA [eicosapentaenoic acid] stabilizes cell membranes and reduces plaque vulnerability and progression.”
REDUCE-IT was sponsored by Amarin. Brigham and Women’s Hospital receives research funding from Amarin for Dr. Bhatt’s role as chair of the trial.
A version of this article originally appeared on Medscape.com.
Aldosterone-driven hypertension found with unexpected frequency
Roughly 16%-22% of patients with hypertension appeared to have primary aldosteronism as the likely major cause of their elevated blood pressure, in an analysis of about 1,000 Americans, which is a much higher prevalence than previously appreciated and a finding that could potentially reorient both screening for aldosteronism and management for this subset of patients.
“Our findings show a high prevalence of unrecognized yet biochemically overt primary aldosteronism [PA] using current confirmatory diagnostic thresholds. They highlight the inadequacy of the current diagnostic approach that heavily relies on the ARR [aldosterone renin ratio] and, most important, show the existence of a pathologic continuum of nonsuppressible renin-independent aldosterone production that parallels the severity of hypertension,” wrote Jennifer M. Brown, MD, and coinvestigators in a report published in Annals of Internal Medicine on May 25. “These findings support the need to redefine primary aldosteronism from a rare and categorical disease to, instead, a common syndrome that manifests across a broad severity spectrum and may be a primary contributor to hypertension pathogenesis,” they wrote in the report.
The results, showing an underappreciated prevalence of both overt and subtler forms of aldosteronism that link with hypertension, won praise from several experts for the potential of these findings to boost the profile of excess aldosterone as a common and treatable cause of high blood pressure, but opinions on the role for the ARR as a screen to identify affected patients were more mixed.
“ARR is still the best screening approach we have” for identifying people who likely have PA, especially when the ratio threshold for finding patients who need further investigation is reduced from the traditional level of 30 ng/dL to 20 ng/dL, commented Michael Stowasser, MBBS, professor of medicine at the University of Queensland in Brisbane, Australia, and director of the Endocrine Hypertension Research Centre at Greenslopes and Princess Alexandra Hospitals in Brisbane. “I strongly recommend ARR testing in all newly diagnosed hypertensives.”
The study results “showed that PA is much more common than previously perceived, and suggest that perhaps PA in milder forms than we typically recognize contributes more to ‘essential’ hypertension than we previously thought,” said Anand Vaidya, MD, senior author of the report and director of the Center for Adrenal Disorders at Brigham and Women’s Hospital in Boston. The researchers found adjusted PA prevalence rates of 16% among 115 untreated patients with stage 1 hypertension (130-139/80-89 mm Hg), 22% among 203 patients with untreated stage 2 hypertension (at least 140/90 mm Hg), and 22% among 408 patients with treatment-resistant hypertension. All three prevalence rates were based on relatively conservative criteria that included all 726 patients with hypertension in the analysis (which also included 289 normotensive subjects) regardless of whether or not they also had low levels of serum renin. These PA prevalence rates were also based on a “conservative” definition of PA, a level of at least 12 mcg excreted in a 24-hour urine specimen.
When the researchers applied less stringent diagnostic criteria for PA or focused on the types of patients usually at highest risk for PA because of a suppressed renin level, the prevalence rates rose substantially and, in some subgroups, more than doubled. Of the 726 people with hypertension included in the analysis, 452 (62%) had suppressed renin (seated plasma renin activity < 1.0 mcg/L per hour or supine plasma renin activity < 0.6 mcg/L per hour). Within this subgroup of patients with suppressed renin, the adjusted prevalence of PA by the threshold of 24-hour urine aldosterone secretion of at least 12 mcg was 52% in those with treatment-resistant hypertension; among patients with stage 1 or 2 hypertension the adjusted prevalence rates were just slightly above the rates in the entire study group. But among patients with suppressed renin who were judged to have PA by a more liberal definition of at least 10 mcg in a 24-hour urine sample, the adjusted prevalence rates were 27% among untreated stage 1 hypertensives, 40% among untreated stage 2 patients, and 58% among treatment-resistant patients, the report showed.
A role for subtler forms of aldosteronism
Defining PA as at least 12 mcg secreted in a 24-hour urine collection “is relatively arbitrary, and our findings show that it bisects a continuous distribution. How we should redefine PA is also arbitrary, but step one is to recognize that many people have milder forms of PA” that could have an important effect on blood pressure, Dr. Vaidya said in an interview.
“This is the very first study to show that aldosterone may be contributing to the hypertensive process even though it is not severe enough to be diagnosed as PA according to current criteria,” said Robert M. Carey, MD, a cardiovascular endocrinologist and professor of medicine at the University of Virginia in Charlottesville and a coauthor on the new report. “More patients than we have ever known have an aldosterone component to their hypertension,” Dr. Carey said in an interview.
The new report on the prevalence of unrecognized PA in hypertensive patients “is a game changer,” wrote John W. Funder, MD, professor of medicine at Monash University in Clayton, Australia, in an editorial published along with the new report. In the editorial, he synthesized the new findings with results from prior reports to estimate that excess aldosteronism could play a clinically meaningful role in close to half of patients with hypertension, although Dr. Stowasser called this an “overestimate.” The new results also showed that “the single spot measurement of plasma aldosterone concentration, which clinicians have used for decades to screen for primary aldosteronism, is not merely useless but actually misleading. The authors cautioned readers about the uncertain representativeness of the study population to the U.S. population, but I believe that the findings are generalizable to the United States and elsewhere,” Dr. Funder wrote. “The central problem is that plasma aldosterone concentration is a very poor index of total daily aldosterone secretion. A single morning spot measurement of plasma aldosterone cannot take into account ultradian variation in aldosterone secretion.”
The importance of finding excess aldosterone
Identifying patients with hypertension and PA, as well as hypertensives with excess aldosterone production that may not meet the traditional definition of PA, is especially important because they are excellent candidates for two forms of targeted and very effective treatments that have a reliable and substantial impact on lowering blood pressure in these patients. One treatment is unilateral adrenal gland removal in patients who produce excess aldosterone because of benign adenomas in one adrenal gland, which accounts for “approximately 30%” of patients with PA. “Patients with suspected PA should have an opportunity to find out whether they have a unilateral variety and chance for surgical cure,” said Dr. Stowasser in an interview. “Patients with PA do far better in terms of blood pressure control, prevention of cardiovascular complications, and quality of life if they are treated specifically, either medically or particularly by surgery.”
The specific medical treatment he cited refers to one of the mineralocorticoid receptor antagonist (MRA) drugs, spironolactone and eplerenone (Inspra), because mineralocorticoid receptor blockade directly short-circuits the path by which aldosterone increases blood pressure. “We’re advocating earlier use of MRAs” for hypertensive patients identified with excess aldosterone production, said Dr. Carey. He noted that alternative, nonsteroidal MRAs, such as finerenone, have shown promise for efficacy levels similar to what spironolactone provides but without as many adverse effects because of greater receptor specificity. Finerenone and other nonsteroidal MRAs are all currently investigational. Spironolactone and eplerenone both cause hyperkalemia, although treatment with potassium binding agents can blunt the risk this poses. Spironolactone also causes bothersome adverse effects in men, including impotence and gynecomastia because of its action on androgen receptors, effects that diminished with eplerenone, but eplerenone is not as effective as spironolactone, Dr. Carey said.
Study details
The new study ran a post hoc analysis on data collected in five independent studies run at centers in four U.S. locations: Birmingham, Ala.; Boston; Charlottesville, Va.; and Salt Lake City. The studies included a total of 1,846 adults, mostly patients with hypertension of varying severity but also several hundred normotensive people. Data on 24-hour sodium excretion during an oral sodium suppression test were available for all participants, and the researchers excluded 831 people with an “inadequate” sodium balance of less than 190 mmol based on this metric, leaving a study population of 1,015. The researchers acknowledged the limitation that the study participants were not representative of the U.S. population.
The analysis included 289 normotensive people not on any blood pressure–lowering medications, and 239 fit the definition of having suppressed renin. The adjusted prevalence of aldosteronism at the level of at least 12 mcg excreted in a 24-hour urine specimen was 11% among all 289 normotensive subjects and 12% among the 239 with suppressed renin. When the definition of aldosteronism loosened to at least 10 mcg excreted during 24 hours the adjusted prevalence of excess aldosterone among normotensives increased to 19% among the entire group and 20% among those with suppressed renin. This finding may have identified a primordial phase of nascent hypertension that needs further study but may eventually provide a new scenario for intervention. “If a normotensive person has compliant arteries and healthy kidneys they can handle the excess salt and volume load of PA,” but when compensatory mechanisms start falling short through aging or other deteriorations, then blood pressure starts to rise, suggested Dr. Vaidya.
Whom to screen for aldosteronism and how
While several experts agreed these findings added to an existing and growing literature showing that PA is common and needs greater diagnostic attention, they differed on what this may mean for the specifics of screening and diagnosis, especially at the primary care level.
“Our results showed more explicitly that excess aldosterone exists on a broad severity spectrum and can’t be regarded as a categorical diagnosis that a patient either has or does not have. The hard part is figuring out where we should begin interventions,” said Dr. Vaidya.
“This publication will hopefully increase clinician awareness of this common and treatable form of hypertension. All people with high blood pressure should be tested at least once for PA,” commented William F. Young Jr., MD, professor and chair of endocrinology at the Mayo Clinic in Rochester, Minn. “Diagnosis of PA provides clinicians with a unique opportunity in medicine, to provide either surgical cure or targeted pharmacotherapy. It’s been frustrating to me to see patients not tested for PA when first diagnosed with hypertension, but only after they developed irreversible chronic kidney disease,” he said in an interview. Dr. Young cited statistics that only about 2% of patients diagnosed with treatment-resistant hypertension are assessed for PA, and only about 3% of patients with hypertension and concomitant hyperkalemia. “Primary care physicians don’t think about PA and don’t test for PA,” he lamented.
The new study “is very convincing, and confirms and extends the findings of several other groups that previously reported the high prevalence of PA among patients with hypertension,” commented Dr. Stowasser. Despite this accumulating evidence, uptake of testing for PA, usually starting with spot measurement of renin and aldosterone to obtain an ARR, has “remained dismally low” among primary care and specialist physicians in Australia, the United States, Europe, and elsewhere, he added.
One stumbling block may be the complexity, or at least perceived complexity, of screening by an ARR and follow-up steps as recommended in a 2016 guideline issued by the Endocrine Society and endorsed by several international medical societies including the American Heart Association, Dr. Carey said. Dr. Funder chaired the task force that wrote the 2016 Endocrine Society PA guideline, and the eight-member task force included Dr. Carey, Dr. Stowasser, and Dr. Young.
The new study highlights what its authors cited as a limitation of the ARR for screening. When set at the frequently used ratio threshold of 30 ng/dL/ng/mL per hour to identify likely cases of PA, the crude PA prevalence rates corresponding to this threshold were 4% in treated stage 1 hypertensives, 10% in treated stage 2 patients, and 7% in those with resistant hypertension, substantially below the adjusted PA prevalence rates calculated by applying different criteria for excess aldosterone. In addition to missing clinically meaningful cases, the ARR may also underachieve at a functional level, Dr. Carey suggested.
“We note the difficulty with point assessment of ARR, but that’s what we have at the moment. We’ll look for other ways to identify patients with excessive aldosterone production,” he said. “We need to design a [diagnostic] pathway that’s easily doable by primary care physicians. Right now it’s pretty complicated. Part of the reason why primary care physicians often don’t screen for PA is the pathway is too complicated. We need to simplify it.”
In his editorial, Dr. Funder wrote that “much of the present guideline needs to be jettisoned, and radically reconstructed recommendations should be developed.”
One answer may be to apply a less stringent ARR threshold for further work-up. Dr. Stowasser’s program in Brisbane, as well as some other groups worldwide, use an ARR of at least 20 ng/dL as an indication of possible PA. “If you lower the cutoff to 20 [ng/dL], and ignore the plasma aldosterone level, then the ARR should pick up the great majority of patients with PA,” he said.
Another controversial aspect is whether aldosterone detection should be screened by 24-hour urine collection or by spot testing. In his editorial, Dr. Funder called spot testing “useless” and “misleading,” but Dr. Vaidya acknowledged that the 24-hour collection used in his current study is “not practical” for widespread use. Despite that, the Mayo Clinic in Rochester has focused on 24-hour urine collected “for more than 4 decades,” said Dr. Young, even though “a morning blood sample remains a simple screening test” that will catch “more than 95% of patients with PA” when combined with a plasma aldosterone threshold of 10 ng/dL. Dr. Stowasser noted that “patients don’t like” 24-hour collection, and not infrequently muck up collection” by forgetting to collect their entire 1-day output. Regardless of its shortcomings, 24-hour urine has the advantage of greater precision and accuracy than spot measurement, and using it on newly diagnosed hypertensive patients who also show renin suppression may be a viable approach, Dr. Carey suggested.
Regardless of exactly how guidelines for assessing aldosterone in hypertensive patients change, prospects seem ripe for some sort of revision and for greater participation and buy-in by primary care physicians than in the past. Dr. Carey, who also served as vice-chair of the American College of Cardiology and American Heart Association Task Force that wrote the most current U.S. guideline for managing hypertension, said it was too soon to revise that document, but the time had come to revise the Endocrine Society’s 2016 guideline for diagnosing and treating PA and to hash out the revision “in partnership” with one or more primary care societies. He also highlighted that publishing the current study in a high-profile primary care journal was an intentional effort to reach a large segment of the primary care community.
The new report “has the potential to change the current state of inertia” over wider PA diagnosis and targeted treatment “by being published in a widely read, major international journal,” commented Dr. Stowasser.
Dr. Vaidya has been a consultant to Catalys Pacific, Corcept Therapeutics, HRA Pharma, Orphagen, and Selenity Therapeutics. None of the other report coauthors had commercial disclosures, including Dr. Carey. Dr. Funder, Dr. Stowasser, and Dr. Young had no disclosures.
SOURCE: Brown JM et al. Ann Int Med. 2020 May 25. doi: 10.7326/M20-0065.
Roughly 16%-22% of patients with hypertension appeared to have primary aldosteronism as the likely major cause of their elevated blood pressure, in an analysis of about 1,000 Americans, which is a much higher prevalence than previously appreciated and a finding that could potentially reorient both screening for aldosteronism and management for this subset of patients.
“Our findings show a high prevalence of unrecognized yet biochemically overt primary aldosteronism [PA] using current confirmatory diagnostic thresholds. They highlight the inadequacy of the current diagnostic approach that heavily relies on the ARR [aldosterone renin ratio] and, most important, show the existence of a pathologic continuum of nonsuppressible renin-independent aldosterone production that parallels the severity of hypertension,” wrote Jennifer M. Brown, MD, and coinvestigators in a report published in Annals of Internal Medicine on May 25. “These findings support the need to redefine primary aldosteronism from a rare and categorical disease to, instead, a common syndrome that manifests across a broad severity spectrum and may be a primary contributor to hypertension pathogenesis,” they wrote in the report.
The results, showing an underappreciated prevalence of both overt and subtler forms of aldosteronism that link with hypertension, won praise from several experts for the potential of these findings to boost the profile of excess aldosterone as a common and treatable cause of high blood pressure, but opinions on the role for the ARR as a screen to identify affected patients were more mixed.
“ARR is still the best screening approach we have” for identifying people who likely have PA, especially when the ratio threshold for finding patients who need further investigation is reduced from the traditional level of 30 ng/dL to 20 ng/dL, commented Michael Stowasser, MBBS, professor of medicine at the University of Queensland in Brisbane, Australia, and director of the Endocrine Hypertension Research Centre at Greenslopes and Princess Alexandra Hospitals in Brisbane. “I strongly recommend ARR testing in all newly diagnosed hypertensives.”
The study results “showed that PA is much more common than previously perceived, and suggest that perhaps PA in milder forms than we typically recognize contributes more to ‘essential’ hypertension than we previously thought,” said Anand Vaidya, MD, senior author of the report and director of the Center for Adrenal Disorders at Brigham and Women’s Hospital in Boston. The researchers found adjusted PA prevalence rates of 16% among 115 untreated patients with stage 1 hypertension (130-139/80-89 mm Hg), 22% among 203 patients with untreated stage 2 hypertension (at least 140/90 mm Hg), and 22% among 408 patients with treatment-resistant hypertension. All three prevalence rates were based on relatively conservative criteria that included all 726 patients with hypertension in the analysis (which also included 289 normotensive subjects) regardless of whether or not they also had low levels of serum renin. These PA prevalence rates were also based on a “conservative” definition of PA, a level of at least 12 mcg excreted in a 24-hour urine specimen.
When the researchers applied less stringent diagnostic criteria for PA or focused on the types of patients usually at highest risk for PA because of a suppressed renin level, the prevalence rates rose substantially and, in some subgroups, more than doubled. Of the 726 people with hypertension included in the analysis, 452 (62%) had suppressed renin (seated plasma renin activity < 1.0 mcg/L per hour or supine plasma renin activity < 0.6 mcg/L per hour). Within this subgroup of patients with suppressed renin, the adjusted prevalence of PA by the threshold of 24-hour urine aldosterone secretion of at least 12 mcg was 52% in those with treatment-resistant hypertension; among patients with stage 1 or 2 hypertension the adjusted prevalence rates were just slightly above the rates in the entire study group. But among patients with suppressed renin who were judged to have PA by a more liberal definition of at least 10 mcg in a 24-hour urine sample, the adjusted prevalence rates were 27% among untreated stage 1 hypertensives, 40% among untreated stage 2 patients, and 58% among treatment-resistant patients, the report showed.
A role for subtler forms of aldosteronism
Defining PA as at least 12 mcg secreted in a 24-hour urine collection “is relatively arbitrary, and our findings show that it bisects a continuous distribution. How we should redefine PA is also arbitrary, but step one is to recognize that many people have milder forms of PA” that could have an important effect on blood pressure, Dr. Vaidya said in an interview.
“This is the very first study to show that aldosterone may be contributing to the hypertensive process even though it is not severe enough to be diagnosed as PA according to current criteria,” said Robert M. Carey, MD, a cardiovascular endocrinologist and professor of medicine at the University of Virginia in Charlottesville and a coauthor on the new report. “More patients than we have ever known have an aldosterone component to their hypertension,” Dr. Carey said in an interview.
The new report on the prevalence of unrecognized PA in hypertensive patients “is a game changer,” wrote John W. Funder, MD, professor of medicine at Monash University in Clayton, Australia, in an editorial published along with the new report. In the editorial, he synthesized the new findings with results from prior reports to estimate that excess aldosteronism could play a clinically meaningful role in close to half of patients with hypertension, although Dr. Stowasser called this an “overestimate.” The new results also showed that “the single spot measurement of plasma aldosterone concentration, which clinicians have used for decades to screen for primary aldosteronism, is not merely useless but actually misleading. The authors cautioned readers about the uncertain representativeness of the study population to the U.S. population, but I believe that the findings are generalizable to the United States and elsewhere,” Dr. Funder wrote. “The central problem is that plasma aldosterone concentration is a very poor index of total daily aldosterone secretion. A single morning spot measurement of plasma aldosterone cannot take into account ultradian variation in aldosterone secretion.”
The importance of finding excess aldosterone
Identifying patients with hypertension and PA, as well as hypertensives with excess aldosterone production that may not meet the traditional definition of PA, is especially important because they are excellent candidates for two forms of targeted and very effective treatments that have a reliable and substantial impact on lowering blood pressure in these patients. One treatment is unilateral adrenal gland removal in patients who produce excess aldosterone because of benign adenomas in one adrenal gland, which accounts for “approximately 30%” of patients with PA. “Patients with suspected PA should have an opportunity to find out whether they have a unilateral variety and chance for surgical cure,” said Dr. Stowasser in an interview. “Patients with PA do far better in terms of blood pressure control, prevention of cardiovascular complications, and quality of life if they are treated specifically, either medically or particularly by surgery.”
The specific medical treatment he cited refers to one of the mineralocorticoid receptor antagonist (MRA) drugs, spironolactone and eplerenone (Inspra), because mineralocorticoid receptor blockade directly short-circuits the path by which aldosterone increases blood pressure. “We’re advocating earlier use of MRAs” for hypertensive patients identified with excess aldosterone production, said Dr. Carey. He noted that alternative, nonsteroidal MRAs, such as finerenone, have shown promise for efficacy levels similar to what spironolactone provides but without as many adverse effects because of greater receptor specificity. Finerenone and other nonsteroidal MRAs are all currently investigational. Spironolactone and eplerenone both cause hyperkalemia, although treatment with potassium binding agents can blunt the risk this poses. Spironolactone also causes bothersome adverse effects in men, including impotence and gynecomastia because of its action on androgen receptors, effects that diminished with eplerenone, but eplerenone is not as effective as spironolactone, Dr. Carey said.
Study details
The new study ran a post hoc analysis on data collected in five independent studies run at centers in four U.S. locations: Birmingham, Ala.; Boston; Charlottesville, Va.; and Salt Lake City. The studies included a total of 1,846 adults, mostly patients with hypertension of varying severity but also several hundred normotensive people. Data on 24-hour sodium excretion during an oral sodium suppression test were available for all participants, and the researchers excluded 831 people with an “inadequate” sodium balance of less than 190 mmol based on this metric, leaving a study population of 1,015. The researchers acknowledged the limitation that the study participants were not representative of the U.S. population.
The analysis included 289 normotensive people not on any blood pressure–lowering medications, and 239 fit the definition of having suppressed renin. The adjusted prevalence of aldosteronism at the level of at least 12 mcg excreted in a 24-hour urine specimen was 11% among all 289 normotensive subjects and 12% among the 239 with suppressed renin. When the definition of aldosteronism loosened to at least 10 mcg excreted during 24 hours the adjusted prevalence of excess aldosterone among normotensives increased to 19% among the entire group and 20% among those with suppressed renin. This finding may have identified a primordial phase of nascent hypertension that needs further study but may eventually provide a new scenario for intervention. “If a normotensive person has compliant arteries and healthy kidneys they can handle the excess salt and volume load of PA,” but when compensatory mechanisms start falling short through aging or other deteriorations, then blood pressure starts to rise, suggested Dr. Vaidya.
Whom to screen for aldosteronism and how
While several experts agreed these findings added to an existing and growing literature showing that PA is common and needs greater diagnostic attention, they differed on what this may mean for the specifics of screening and diagnosis, especially at the primary care level.
“Our results showed more explicitly that excess aldosterone exists on a broad severity spectrum and can’t be regarded as a categorical diagnosis that a patient either has or does not have. The hard part is figuring out where we should begin interventions,” said Dr. Vaidya.
“This publication will hopefully increase clinician awareness of this common and treatable form of hypertension. All people with high blood pressure should be tested at least once for PA,” commented William F. Young Jr., MD, professor and chair of endocrinology at the Mayo Clinic in Rochester, Minn. “Diagnosis of PA provides clinicians with a unique opportunity in medicine, to provide either surgical cure or targeted pharmacotherapy. It’s been frustrating to me to see patients not tested for PA when first diagnosed with hypertension, but only after they developed irreversible chronic kidney disease,” he said in an interview. Dr. Young cited statistics that only about 2% of patients diagnosed with treatment-resistant hypertension are assessed for PA, and only about 3% of patients with hypertension and concomitant hyperkalemia. “Primary care physicians don’t think about PA and don’t test for PA,” he lamented.
The new study “is very convincing, and confirms and extends the findings of several other groups that previously reported the high prevalence of PA among patients with hypertension,” commented Dr. Stowasser. Despite this accumulating evidence, uptake of testing for PA, usually starting with spot measurement of renin and aldosterone to obtain an ARR, has “remained dismally low” among primary care and specialist physicians in Australia, the United States, Europe, and elsewhere, he added.
One stumbling block may be the complexity, or at least perceived complexity, of screening by an ARR and follow-up steps as recommended in a 2016 guideline issued by the Endocrine Society and endorsed by several international medical societies including the American Heart Association, Dr. Carey said. Dr. Funder chaired the task force that wrote the 2016 Endocrine Society PA guideline, and the eight-member task force included Dr. Carey, Dr. Stowasser, and Dr. Young.
The new study highlights what its authors cited as a limitation of the ARR for screening. When set at the frequently used ratio threshold of 30 ng/dL/ng/mL per hour to identify likely cases of PA, the crude PA prevalence rates corresponding to this threshold were 4% in treated stage 1 hypertensives, 10% in treated stage 2 patients, and 7% in those with resistant hypertension, substantially below the adjusted PA prevalence rates calculated by applying different criteria for excess aldosterone. In addition to missing clinically meaningful cases, the ARR may also underachieve at a functional level, Dr. Carey suggested.
“We note the difficulty with point assessment of ARR, but that’s what we have at the moment. We’ll look for other ways to identify patients with excessive aldosterone production,” he said. “We need to design a [diagnostic] pathway that’s easily doable by primary care physicians. Right now it’s pretty complicated. Part of the reason why primary care physicians often don’t screen for PA is the pathway is too complicated. We need to simplify it.”
In his editorial, Dr. Funder wrote that “much of the present guideline needs to be jettisoned, and radically reconstructed recommendations should be developed.”
One answer may be to apply a less stringent ARR threshold for further work-up. Dr. Stowasser’s program in Brisbane, as well as some other groups worldwide, use an ARR of at least 20 ng/dL as an indication of possible PA. “If you lower the cutoff to 20 [ng/dL], and ignore the plasma aldosterone level, then the ARR should pick up the great majority of patients with PA,” he said.
Another controversial aspect is whether aldosterone detection should be screened by 24-hour urine collection or by spot testing. In his editorial, Dr. Funder called spot testing “useless” and “misleading,” but Dr. Vaidya acknowledged that the 24-hour collection used in his current study is “not practical” for widespread use. Despite that, the Mayo Clinic in Rochester has focused on 24-hour urine collected “for more than 4 decades,” said Dr. Young, even though “a morning blood sample remains a simple screening test” that will catch “more than 95% of patients with PA” when combined with a plasma aldosterone threshold of 10 ng/dL. Dr. Stowasser noted that “patients don’t like” 24-hour collection, and not infrequently muck up collection” by forgetting to collect their entire 1-day output. Regardless of its shortcomings, 24-hour urine has the advantage of greater precision and accuracy than spot measurement, and using it on newly diagnosed hypertensive patients who also show renin suppression may be a viable approach, Dr. Carey suggested.
Regardless of exactly how guidelines for assessing aldosterone in hypertensive patients change, prospects seem ripe for some sort of revision and for greater participation and buy-in by primary care physicians than in the past. Dr. Carey, who also served as vice-chair of the American College of Cardiology and American Heart Association Task Force that wrote the most current U.S. guideline for managing hypertension, said it was too soon to revise that document, but the time had come to revise the Endocrine Society’s 2016 guideline for diagnosing and treating PA and to hash out the revision “in partnership” with one or more primary care societies. He also highlighted that publishing the current study in a high-profile primary care journal was an intentional effort to reach a large segment of the primary care community.
The new report “has the potential to change the current state of inertia” over wider PA diagnosis and targeted treatment “by being published in a widely read, major international journal,” commented Dr. Stowasser.
Dr. Vaidya has been a consultant to Catalys Pacific, Corcept Therapeutics, HRA Pharma, Orphagen, and Selenity Therapeutics. None of the other report coauthors had commercial disclosures, including Dr. Carey. Dr. Funder, Dr. Stowasser, and Dr. Young had no disclosures.
SOURCE: Brown JM et al. Ann Int Med. 2020 May 25. doi: 10.7326/M20-0065.
Roughly 16%-22% of patients with hypertension appeared to have primary aldosteronism as the likely major cause of their elevated blood pressure, in an analysis of about 1,000 Americans, which is a much higher prevalence than previously appreciated and a finding that could potentially reorient both screening for aldosteronism and management for this subset of patients.
“Our findings show a high prevalence of unrecognized yet biochemically overt primary aldosteronism [PA] using current confirmatory diagnostic thresholds. They highlight the inadequacy of the current diagnostic approach that heavily relies on the ARR [aldosterone renin ratio] and, most important, show the existence of a pathologic continuum of nonsuppressible renin-independent aldosterone production that parallels the severity of hypertension,” wrote Jennifer M. Brown, MD, and coinvestigators in a report published in Annals of Internal Medicine on May 25. “These findings support the need to redefine primary aldosteronism from a rare and categorical disease to, instead, a common syndrome that manifests across a broad severity spectrum and may be a primary contributor to hypertension pathogenesis,” they wrote in the report.
The results, showing an underappreciated prevalence of both overt and subtler forms of aldosteronism that link with hypertension, won praise from several experts for the potential of these findings to boost the profile of excess aldosterone as a common and treatable cause of high blood pressure, but opinions on the role for the ARR as a screen to identify affected patients were more mixed.
“ARR is still the best screening approach we have” for identifying people who likely have PA, especially when the ratio threshold for finding patients who need further investigation is reduced from the traditional level of 30 ng/dL to 20 ng/dL, commented Michael Stowasser, MBBS, professor of medicine at the University of Queensland in Brisbane, Australia, and director of the Endocrine Hypertension Research Centre at Greenslopes and Princess Alexandra Hospitals in Brisbane. “I strongly recommend ARR testing in all newly diagnosed hypertensives.”
The study results “showed that PA is much more common than previously perceived, and suggest that perhaps PA in milder forms than we typically recognize contributes more to ‘essential’ hypertension than we previously thought,” said Anand Vaidya, MD, senior author of the report and director of the Center for Adrenal Disorders at Brigham and Women’s Hospital in Boston. The researchers found adjusted PA prevalence rates of 16% among 115 untreated patients with stage 1 hypertension (130-139/80-89 mm Hg), 22% among 203 patients with untreated stage 2 hypertension (at least 140/90 mm Hg), and 22% among 408 patients with treatment-resistant hypertension. All three prevalence rates were based on relatively conservative criteria that included all 726 patients with hypertension in the analysis (which also included 289 normotensive subjects) regardless of whether or not they also had low levels of serum renin. These PA prevalence rates were also based on a “conservative” definition of PA, a level of at least 12 mcg excreted in a 24-hour urine specimen.
When the researchers applied less stringent diagnostic criteria for PA or focused on the types of patients usually at highest risk for PA because of a suppressed renin level, the prevalence rates rose substantially and, in some subgroups, more than doubled. Of the 726 people with hypertension included in the analysis, 452 (62%) had suppressed renin (seated plasma renin activity < 1.0 mcg/L per hour or supine plasma renin activity < 0.6 mcg/L per hour). Within this subgroup of patients with suppressed renin, the adjusted prevalence of PA by the threshold of 24-hour urine aldosterone secretion of at least 12 mcg was 52% in those with treatment-resistant hypertension; among patients with stage 1 or 2 hypertension the adjusted prevalence rates were just slightly above the rates in the entire study group. But among patients with suppressed renin who were judged to have PA by a more liberal definition of at least 10 mcg in a 24-hour urine sample, the adjusted prevalence rates were 27% among untreated stage 1 hypertensives, 40% among untreated stage 2 patients, and 58% among treatment-resistant patients, the report showed.
A role for subtler forms of aldosteronism
Defining PA as at least 12 mcg secreted in a 24-hour urine collection “is relatively arbitrary, and our findings show that it bisects a continuous distribution. How we should redefine PA is also arbitrary, but step one is to recognize that many people have milder forms of PA” that could have an important effect on blood pressure, Dr. Vaidya said in an interview.
“This is the very first study to show that aldosterone may be contributing to the hypertensive process even though it is not severe enough to be diagnosed as PA according to current criteria,” said Robert M. Carey, MD, a cardiovascular endocrinologist and professor of medicine at the University of Virginia in Charlottesville and a coauthor on the new report. “More patients than we have ever known have an aldosterone component to their hypertension,” Dr. Carey said in an interview.
The new report on the prevalence of unrecognized PA in hypertensive patients “is a game changer,” wrote John W. Funder, MD, professor of medicine at Monash University in Clayton, Australia, in an editorial published along with the new report. In the editorial, he synthesized the new findings with results from prior reports to estimate that excess aldosteronism could play a clinically meaningful role in close to half of patients with hypertension, although Dr. Stowasser called this an “overestimate.” The new results also showed that “the single spot measurement of plasma aldosterone concentration, which clinicians have used for decades to screen for primary aldosteronism, is not merely useless but actually misleading. The authors cautioned readers about the uncertain representativeness of the study population to the U.S. population, but I believe that the findings are generalizable to the United States and elsewhere,” Dr. Funder wrote. “The central problem is that plasma aldosterone concentration is a very poor index of total daily aldosterone secretion. A single morning spot measurement of plasma aldosterone cannot take into account ultradian variation in aldosterone secretion.”
The importance of finding excess aldosterone
Identifying patients with hypertension and PA, as well as hypertensives with excess aldosterone production that may not meet the traditional definition of PA, is especially important because they are excellent candidates for two forms of targeted and very effective treatments that have a reliable and substantial impact on lowering blood pressure in these patients. One treatment is unilateral adrenal gland removal in patients who produce excess aldosterone because of benign adenomas in one adrenal gland, which accounts for “approximately 30%” of patients with PA. “Patients with suspected PA should have an opportunity to find out whether they have a unilateral variety and chance for surgical cure,” said Dr. Stowasser in an interview. “Patients with PA do far better in terms of blood pressure control, prevention of cardiovascular complications, and quality of life if they are treated specifically, either medically or particularly by surgery.”
The specific medical treatment he cited refers to one of the mineralocorticoid receptor antagonist (MRA) drugs, spironolactone and eplerenone (Inspra), because mineralocorticoid receptor blockade directly short-circuits the path by which aldosterone increases blood pressure. “We’re advocating earlier use of MRAs” for hypertensive patients identified with excess aldosterone production, said Dr. Carey. He noted that alternative, nonsteroidal MRAs, such as finerenone, have shown promise for efficacy levels similar to what spironolactone provides but without as many adverse effects because of greater receptor specificity. Finerenone and other nonsteroidal MRAs are all currently investigational. Spironolactone and eplerenone both cause hyperkalemia, although treatment with potassium binding agents can blunt the risk this poses. Spironolactone also causes bothersome adverse effects in men, including impotence and gynecomastia because of its action on androgen receptors, effects that diminished with eplerenone, but eplerenone is not as effective as spironolactone, Dr. Carey said.
Study details
The new study ran a post hoc analysis on data collected in five independent studies run at centers in four U.S. locations: Birmingham, Ala.; Boston; Charlottesville, Va.; and Salt Lake City. The studies included a total of 1,846 adults, mostly patients with hypertension of varying severity but also several hundred normotensive people. Data on 24-hour sodium excretion during an oral sodium suppression test were available for all participants, and the researchers excluded 831 people with an “inadequate” sodium balance of less than 190 mmol based on this metric, leaving a study population of 1,015. The researchers acknowledged the limitation that the study participants were not representative of the U.S. population.
The analysis included 289 normotensive people not on any blood pressure–lowering medications, and 239 fit the definition of having suppressed renin. The adjusted prevalence of aldosteronism at the level of at least 12 mcg excreted in a 24-hour urine specimen was 11% among all 289 normotensive subjects and 12% among the 239 with suppressed renin. When the definition of aldosteronism loosened to at least 10 mcg excreted during 24 hours the adjusted prevalence of excess aldosterone among normotensives increased to 19% among the entire group and 20% among those with suppressed renin. This finding may have identified a primordial phase of nascent hypertension that needs further study but may eventually provide a new scenario for intervention. “If a normotensive person has compliant arteries and healthy kidneys they can handle the excess salt and volume load of PA,” but when compensatory mechanisms start falling short through aging or other deteriorations, then blood pressure starts to rise, suggested Dr. Vaidya.
Whom to screen for aldosteronism and how
While several experts agreed these findings added to an existing and growing literature showing that PA is common and needs greater diagnostic attention, they differed on what this may mean for the specifics of screening and diagnosis, especially at the primary care level.
“Our results showed more explicitly that excess aldosterone exists on a broad severity spectrum and can’t be regarded as a categorical diagnosis that a patient either has or does not have. The hard part is figuring out where we should begin interventions,” said Dr. Vaidya.
“This publication will hopefully increase clinician awareness of this common and treatable form of hypertension. All people with high blood pressure should be tested at least once for PA,” commented William F. Young Jr., MD, professor and chair of endocrinology at the Mayo Clinic in Rochester, Minn. “Diagnosis of PA provides clinicians with a unique opportunity in medicine, to provide either surgical cure or targeted pharmacotherapy. It’s been frustrating to me to see patients not tested for PA when first diagnosed with hypertension, but only after they developed irreversible chronic kidney disease,” he said in an interview. Dr. Young cited statistics that only about 2% of patients diagnosed with treatment-resistant hypertension are assessed for PA, and only about 3% of patients with hypertension and concomitant hyperkalemia. “Primary care physicians don’t think about PA and don’t test for PA,” he lamented.
The new study “is very convincing, and confirms and extends the findings of several other groups that previously reported the high prevalence of PA among patients with hypertension,” commented Dr. Stowasser. Despite this accumulating evidence, uptake of testing for PA, usually starting with spot measurement of renin and aldosterone to obtain an ARR, has “remained dismally low” among primary care and specialist physicians in Australia, the United States, Europe, and elsewhere, he added.
One stumbling block may be the complexity, or at least perceived complexity, of screening by an ARR and follow-up steps as recommended in a 2016 guideline issued by the Endocrine Society and endorsed by several international medical societies including the American Heart Association, Dr. Carey said. Dr. Funder chaired the task force that wrote the 2016 Endocrine Society PA guideline, and the eight-member task force included Dr. Carey, Dr. Stowasser, and Dr. Young.
The new study highlights what its authors cited as a limitation of the ARR for screening. When set at the frequently used ratio threshold of 30 ng/dL/ng/mL per hour to identify likely cases of PA, the crude PA prevalence rates corresponding to this threshold were 4% in treated stage 1 hypertensives, 10% in treated stage 2 patients, and 7% in those with resistant hypertension, substantially below the adjusted PA prevalence rates calculated by applying different criteria for excess aldosterone. In addition to missing clinically meaningful cases, the ARR may also underachieve at a functional level, Dr. Carey suggested.
“We note the difficulty with point assessment of ARR, but that’s what we have at the moment. We’ll look for other ways to identify patients with excessive aldosterone production,” he said. “We need to design a [diagnostic] pathway that’s easily doable by primary care physicians. Right now it’s pretty complicated. Part of the reason why primary care physicians often don’t screen for PA is the pathway is too complicated. We need to simplify it.”
In his editorial, Dr. Funder wrote that “much of the present guideline needs to be jettisoned, and radically reconstructed recommendations should be developed.”
One answer may be to apply a less stringent ARR threshold for further work-up. Dr. Stowasser’s program in Brisbane, as well as some other groups worldwide, use an ARR of at least 20 ng/dL as an indication of possible PA. “If you lower the cutoff to 20 [ng/dL], and ignore the plasma aldosterone level, then the ARR should pick up the great majority of patients with PA,” he said.
Another controversial aspect is whether aldosterone detection should be screened by 24-hour urine collection or by spot testing. In his editorial, Dr. Funder called spot testing “useless” and “misleading,” but Dr. Vaidya acknowledged that the 24-hour collection used in his current study is “not practical” for widespread use. Despite that, the Mayo Clinic in Rochester has focused on 24-hour urine collected “for more than 4 decades,” said Dr. Young, even though “a morning blood sample remains a simple screening test” that will catch “more than 95% of patients with PA” when combined with a plasma aldosterone threshold of 10 ng/dL. Dr. Stowasser noted that “patients don’t like” 24-hour collection, and not infrequently muck up collection” by forgetting to collect their entire 1-day output. Regardless of its shortcomings, 24-hour urine has the advantage of greater precision and accuracy than spot measurement, and using it on newly diagnosed hypertensive patients who also show renin suppression may be a viable approach, Dr. Carey suggested.
Regardless of exactly how guidelines for assessing aldosterone in hypertensive patients change, prospects seem ripe for some sort of revision and for greater participation and buy-in by primary care physicians than in the past. Dr. Carey, who also served as vice-chair of the American College of Cardiology and American Heart Association Task Force that wrote the most current U.S. guideline for managing hypertension, said it was too soon to revise that document, but the time had come to revise the Endocrine Society’s 2016 guideline for diagnosing and treating PA and to hash out the revision “in partnership” with one or more primary care societies. He also highlighted that publishing the current study in a high-profile primary care journal was an intentional effort to reach a large segment of the primary care community.
The new report “has the potential to change the current state of inertia” over wider PA diagnosis and targeted treatment “by being published in a widely read, major international journal,” commented Dr. Stowasser.
Dr. Vaidya has been a consultant to Catalys Pacific, Corcept Therapeutics, HRA Pharma, Orphagen, and Selenity Therapeutics. None of the other report coauthors had commercial disclosures, including Dr. Carey. Dr. Funder, Dr. Stowasser, and Dr. Young had no disclosures.
SOURCE: Brown JM et al. Ann Int Med. 2020 May 25. doi: 10.7326/M20-0065.
REPORTING FROM ANNALS OF INTERNAL MEDICINE
Social isolation tied to higher risk of cardiovascular events, death
“These results are especially important in the current times of social isolation during the coronavirus crisis,” Janine Gronewold, PhD, University Hospital in Essen, Germany, told a press briefing.
The mechanism by which social isolation may boost risk for stroke, MI, or death is not clear, but other research has shown that loneliness or lack of contact with close friends and family can affect physical health, said Dr. Gronewold.
The findings were presented at the sixth Congress of the European Academy of Neurology (EAN) 2020, which transitioned to a virtual/online meeting because of the COVID-19 pandemic.
For this new study, researchers analyzed data from 4,139 participants, ranging in age from 45 to 75 years (mean 59.1 years), who were recruited into the large community-based Heinz Nixdorf Recall study. The randomly selected study group was representative of an industrial rural area of Germany, said Dr. Gronewold.
Study participants entered the study with no known cardiovascular disease and were followed for a mean of 13.4 years.
Social supports
Investigators collected information on three types of social support: instrumental (getting help with everyday activities such as buying food), emotional (provided with comfort), and financial (receiving monetary assistance when needed). They also looked at social integration (or social isolation) using an index with scores for marital status, number of contacts with family and friends, and membership in political, religious, community, sports, or professional associations.
Of the total, 501 participants reported a lack of instrumental support, 659 a lack of emotional support, and 907 a lack of financial support. A total of 309 lacked social integration, defined by the lowest level on the social integration index.
Participants were asked annually about new cardiovascular events, including stroke and MI. Over the follow-up period, there were 339 such events and 530 deaths.
After adjustment for age, sex, and social support, the analysis showed that social isolation was significantly associated with an increased risk of cardiovascular events (hazard ratio, 1.44; 95% confidence interval, 0.97-2.14) and all-cause mortality (HR, 1.47; 95% CI, 1.09-1.97).
The new research also showed that lack of financial support was significantly associated with increased risk for a cardiovascular event (HR, 1.30; 95% CI, 1.01-1.67).
Direct effect
Additional models that also adjusted for cardiovascular risk factors, health behaviors, depression, and socioeconomic factors, did not significantly change effect estimates.
“Social relationships protect us from cardiovascular events and mortality, not only via good mood, healthy behavior, and lower cardiovascular risk profile,” Dr. Gronewold said. “They seem to have a direct effect on these outcomes.”
Having strong social relationships is as important to cardiovascular health as classic protective factors such as controlling blood pressure and cholesterol levels, and maintaining a normal weight, said Dr. Gronewold.
The new results are worrying and are particularly important during the current COVID-19 pandemic, as social contact has been restricted in many areas, said Dr. Gronewold.
It is not yet clear why people who are socially isolated have such poor health outcomes, she added.
Dr. Gronewold has reported no relevant financial relationships.
This article first appeared on Medscape.com.
“These results are especially important in the current times of social isolation during the coronavirus crisis,” Janine Gronewold, PhD, University Hospital in Essen, Germany, told a press briefing.
The mechanism by which social isolation may boost risk for stroke, MI, or death is not clear, but other research has shown that loneliness or lack of contact with close friends and family can affect physical health, said Dr. Gronewold.
The findings were presented at the sixth Congress of the European Academy of Neurology (EAN) 2020, which transitioned to a virtual/online meeting because of the COVID-19 pandemic.
For this new study, researchers analyzed data from 4,139 participants, ranging in age from 45 to 75 years (mean 59.1 years), who were recruited into the large community-based Heinz Nixdorf Recall study. The randomly selected study group was representative of an industrial rural area of Germany, said Dr. Gronewold.
Study participants entered the study with no known cardiovascular disease and were followed for a mean of 13.4 years.
Social supports
Investigators collected information on three types of social support: instrumental (getting help with everyday activities such as buying food), emotional (provided with comfort), and financial (receiving monetary assistance when needed). They also looked at social integration (or social isolation) using an index with scores for marital status, number of contacts with family and friends, and membership in political, religious, community, sports, or professional associations.
Of the total, 501 participants reported a lack of instrumental support, 659 a lack of emotional support, and 907 a lack of financial support. A total of 309 lacked social integration, defined by the lowest level on the social integration index.
Participants were asked annually about new cardiovascular events, including stroke and MI. Over the follow-up period, there were 339 such events and 530 deaths.
After adjustment for age, sex, and social support, the analysis showed that social isolation was significantly associated with an increased risk of cardiovascular events (hazard ratio, 1.44; 95% confidence interval, 0.97-2.14) and all-cause mortality (HR, 1.47; 95% CI, 1.09-1.97).
The new research also showed that lack of financial support was significantly associated with increased risk for a cardiovascular event (HR, 1.30; 95% CI, 1.01-1.67).
Direct effect
Additional models that also adjusted for cardiovascular risk factors, health behaviors, depression, and socioeconomic factors, did not significantly change effect estimates.
“Social relationships protect us from cardiovascular events and mortality, not only via good mood, healthy behavior, and lower cardiovascular risk profile,” Dr. Gronewold said. “They seem to have a direct effect on these outcomes.”
Having strong social relationships is as important to cardiovascular health as classic protective factors such as controlling blood pressure and cholesterol levels, and maintaining a normal weight, said Dr. Gronewold.
The new results are worrying and are particularly important during the current COVID-19 pandemic, as social contact has been restricted in many areas, said Dr. Gronewold.
It is not yet clear why people who are socially isolated have such poor health outcomes, she added.
Dr. Gronewold has reported no relevant financial relationships.
This article first appeared on Medscape.com.
“These results are especially important in the current times of social isolation during the coronavirus crisis,” Janine Gronewold, PhD, University Hospital in Essen, Germany, told a press briefing.
The mechanism by which social isolation may boost risk for stroke, MI, or death is not clear, but other research has shown that loneliness or lack of contact with close friends and family can affect physical health, said Dr. Gronewold.
The findings were presented at the sixth Congress of the European Academy of Neurology (EAN) 2020, which transitioned to a virtual/online meeting because of the COVID-19 pandemic.
For this new study, researchers analyzed data from 4,139 participants, ranging in age from 45 to 75 years (mean 59.1 years), who were recruited into the large community-based Heinz Nixdorf Recall study. The randomly selected study group was representative of an industrial rural area of Germany, said Dr. Gronewold.
Study participants entered the study with no known cardiovascular disease and were followed for a mean of 13.4 years.
Social supports
Investigators collected information on three types of social support: instrumental (getting help with everyday activities such as buying food), emotional (provided with comfort), and financial (receiving monetary assistance when needed). They also looked at social integration (or social isolation) using an index with scores for marital status, number of contacts with family and friends, and membership in political, religious, community, sports, or professional associations.
Of the total, 501 participants reported a lack of instrumental support, 659 a lack of emotional support, and 907 a lack of financial support. A total of 309 lacked social integration, defined by the lowest level on the social integration index.
Participants were asked annually about new cardiovascular events, including stroke and MI. Over the follow-up period, there were 339 such events and 530 deaths.
After adjustment for age, sex, and social support, the analysis showed that social isolation was significantly associated with an increased risk of cardiovascular events (hazard ratio, 1.44; 95% confidence interval, 0.97-2.14) and all-cause mortality (HR, 1.47; 95% CI, 1.09-1.97).
The new research also showed that lack of financial support was significantly associated with increased risk for a cardiovascular event (HR, 1.30; 95% CI, 1.01-1.67).
Direct effect
Additional models that also adjusted for cardiovascular risk factors, health behaviors, depression, and socioeconomic factors, did not significantly change effect estimates.
“Social relationships protect us from cardiovascular events and mortality, not only via good mood, healthy behavior, and lower cardiovascular risk profile,” Dr. Gronewold said. “They seem to have a direct effect on these outcomes.”
Having strong social relationships is as important to cardiovascular health as classic protective factors such as controlling blood pressure and cholesterol levels, and maintaining a normal weight, said Dr. Gronewold.
The new results are worrying and are particularly important during the current COVID-19 pandemic, as social contact has been restricted in many areas, said Dr. Gronewold.
It is not yet clear why people who are socially isolated have such poor health outcomes, she added.
Dr. Gronewold has reported no relevant financial relationships.
This article first appeared on Medscape.com.
FROM EAN 2020
More evidence hydroxychloroquine is ineffective, harmful in COVID-19
Hydroxychloroquine and chloroquine, with or without azithromycin or clarithromycin, offer no benefit in treating patients with COVID-19 and, instead, are associated with ventricular arrhythmias and higher rates of mortality, according to a major new international study.
In the largest observational study of its kind, including close to 100,000 people in 671 hospitals on six continents, investigators compared outcomes in 15,000 patients with COVID-19 treated with hydroxychloroquine and chloroquine alone or in combination with a macrolide with 80,000 control patients with COVID-19 not receiving these agents.
Treatment with any of these medications, either alone or in combination, was associated with increased death during hospitalization; compared with about 10% in control group patients, mortality rates ranged from more than 16% to almost 24% in the treated groups.
Patients treated with hydroxychloroquine plus a macrolide showed the highest rates of serious cardiac arrhythmias, and, even after accounting for demographic factors and comorbidities, this combination was found to be associated with a more than 5-fold increase in the risk of developing a serious arrhythmia while in the hospital.
“In this real-world study, the biggest yet, we looked at 100,000 patients [with COVID-19] across six continents and found not the slightest hint of benefits and only risks, and the data is pretty straightforward,” study coauthor Frank Ruschitzka, MD, director of the Heart Center at University Hospital, Zürich, said in an interview. The study was published online May 22 in The Lancet.
‘Inconclusive’ evidence
The absence of an effective treatment for COVID-19 has led to the “repurposing” of the antimalarial drug chloroquine and its analogue hydroxychloroquine, which is used for treating autoimmune disease, but this approach is based on anecdotal evidence or open-label randomized trials that have been “largely inconclusive,” the authors wrote.
Additional agents used to treat COVID-19 are second-generation macrolides (azithromycin or clarithromycin), in combination with chloroquine or hydroxychloroquine, “despite limited evidence” and the risk for ventricular arrhythmias, the authors noted.
“Our primary question was whether there was any associated benefits of the use of hydroxychloroquine, chloroquine, or a combined regimen with macrolides in treating COVID-19, and — if there was no benefit — would there be harm?” lead author Mandeep R. Mehra, MD, MSc, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, said in an interview.
The investigators used data from a multinational registry comprising 671 hospitals that included patients (n = 96,032; mean age 53.8 years; 46.3% female) who had been hospitalized between Dec. 20, 2019, and April 14, 2020, with confirmed COVID-19 infection.
They also collected data about demographics, underlying comorbidities, and medical history, and medications that patients were taking at baseline.
Patients receiving treatment (n = 14,888) were divided into four groups: those receiving chloroquine alone (n = 1,868), those receiving chloroquine with a macrolide (n = 3,783), those receiving hydroxychloroquine alone (n = 3,016) and those receiving hydroxychloroquine with a macrolide (n = 6,221).
The remaining patients not treated with these regimens (n = 81,144) were regarded as the control group.
Most patients (65.9%) came from North America, followed by Europe (17.39%), Asia (7.9%), Africa (4.6%), South America (3.7%), and Australia (0.6%). Most (66.9%) were white, followed by patients of Asian origin (14.1%), black patients (9.4%), and Hispanic patients (6.2%).
Comorbidities and underlying conditions included obesity, hyperlipidemia, and hypertension in about 30%.
Comorbidities and underlying conditions
The investigators conducted multiple analyses to control for confounding variables, including Cox proportional hazards regression and propensity score matching analyses.
“In an observational study, there is always a chance of residual confounding, which is why we did propensity score based matched analyses,” Dr. Ruschitzka explained.
No significant differences were found in distribution of demographics and comorbidities between the groups.
As good as it gets
“We found no benefit in any of the four treatment regimens for hospitalized patients with COVID-19, but we did notice higher rates of death and serious ventricular arrhythmias in these patients, compared to the controls,” Dr. Mehra reported.
Of the patients in the control group, roughly 9.3% died during their hospitalization, compared with 16.4% of patients treated with chloroquine alone, 18.0% of those treated with hydroxychloroquine alone, 22.2% of those treated with chloroquine and a macrolide, and 23.8% of those treated with hydroxychloroquine and a macrolide.
After accounting for confounding variables, the researchers estimated that the excess mortality risk attributable to use of the drug regimen ranged from 34% to 45%.
Patients treated with any of the four regimens sustained more serious arrhythmias, compared with those in the control group (0.35), with the biggest increase seen in the group treated with the combination of hydroxychloroquine plus a macrolide (8.1%), followed by chloroquine with a macrolide (6.5%), hydroxychloroquine alone (6.1%), and chloroquine alone (4.3%).
“We were fairly reassured that, although the study was observational, the signals were robust and consistent across all regions of the world in diverse populations, and we did not see any muting of that signal, depending on region,” Dr. Mehra said.
“Two months ago, we were all scratching our heads about how to treat patients with COVID-19, and then came a drug [hydroxychloroquine] with some anecdotal evidence, but now we have 2 months more experience, and we looked to science to provide some answer,” Dr. Ruschitzka said.
“Although this was not a randomized, controlled trial, so we do not have a definite answer, the data provided in this [large, multinational] real-world study is as good as it gets and the best data we have,” he concluded.
“Let the science speak for itself”
Commenting on the study in an interview, Christian Funck-Brentano, MD, from the Hospital Pitié-Salpêtrière and Sorbonne University, both in Paris, said that, although the study is observational and therefore not as reliable as a randomized controlled trial, it is “nevertheless well-documented, studied a huge amount of people, and utilized several sensitivity methods, all of which showed the same results.”
Dr. Funck-Brentano, who is the coauthor of an accompanying editorial in The Lancet and was not involved with the study, said that “we now have no evidence that hydroxychloroquine and chloroquine alone or in combination with a macrolide do any good and we have potential evidence that they do harm and kill people.”
Also commenting on the study in an interview, David Holtgrave, PhD, dean of the School of Public Health at the State University of New York at Albany, said that, “while no one observational study alone would lead to a firm clinical recommendation, I think it is helpful for physicians and public health officials to be aware of the findings of the peer-reviewed observational studies to date and the National Institutes of Health COVID-19 treatment guidelines and the Food and Drug Administration’s statement of drug safety concern about hydroxychloroquine to inform their decision-making as we await the results of randomized clinical trials of these drugs for the treatment of COVID-19,” said Dr. Holtgrave, who was not involved with the study.
He added that, to his knowledge, there are “still no published studies of prophylactic use of these drugs to prevent COVID-19.”
Dr. Mehra emphasized that a cardinal principle of practicing medicine is “first do no harm” and “even in situations where you believe a desperate disease calls for desperate measures, responsible physicians should take a step back and ask if we are doing harm, and until we can say we aren’t, I don’t think it’s wise to push something like this in the absence of good efficacy data.”
Dr. Ruschitzka added that those who are encouraging the use of these agents “should review their decision based on today’s data and let the science speak for itself.”
The study was supported by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital, Boston. Dr. Mehra reported personal fees from Abbott, Medtronic, Janssen, Mesoblast, Portola, Bayer, Baim Institute for Clinical Research, NuPulseCV, FineHeart, Leviticus, Roivant, and Triple Gene. Dr. Ruschitzka was paid for time spent as a committee member for clinical trials, advisory boards, other forms of consulting, and lectures or presentations; these payments were made directly to the University of Zürich and no personal payments were received in relation to these trials or other activities. Dr. Funck-Brentano, his coauthor, and Dr. Holtgrave declared no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Hydroxychloroquine and chloroquine, with or without azithromycin or clarithromycin, offer no benefit in treating patients with COVID-19 and, instead, are associated with ventricular arrhythmias and higher rates of mortality, according to a major new international study.
In the largest observational study of its kind, including close to 100,000 people in 671 hospitals on six continents, investigators compared outcomes in 15,000 patients with COVID-19 treated with hydroxychloroquine and chloroquine alone or in combination with a macrolide with 80,000 control patients with COVID-19 not receiving these agents.
Treatment with any of these medications, either alone or in combination, was associated with increased death during hospitalization; compared with about 10% in control group patients, mortality rates ranged from more than 16% to almost 24% in the treated groups.
Patients treated with hydroxychloroquine plus a macrolide showed the highest rates of serious cardiac arrhythmias, and, even after accounting for demographic factors and comorbidities, this combination was found to be associated with a more than 5-fold increase in the risk of developing a serious arrhythmia while in the hospital.
“In this real-world study, the biggest yet, we looked at 100,000 patients [with COVID-19] across six continents and found not the slightest hint of benefits and only risks, and the data is pretty straightforward,” study coauthor Frank Ruschitzka, MD, director of the Heart Center at University Hospital, Zürich, said in an interview. The study was published online May 22 in The Lancet.
‘Inconclusive’ evidence
The absence of an effective treatment for COVID-19 has led to the “repurposing” of the antimalarial drug chloroquine and its analogue hydroxychloroquine, which is used for treating autoimmune disease, but this approach is based on anecdotal evidence or open-label randomized trials that have been “largely inconclusive,” the authors wrote.
Additional agents used to treat COVID-19 are second-generation macrolides (azithromycin or clarithromycin), in combination with chloroquine or hydroxychloroquine, “despite limited evidence” and the risk for ventricular arrhythmias, the authors noted.
“Our primary question was whether there was any associated benefits of the use of hydroxychloroquine, chloroquine, or a combined regimen with macrolides in treating COVID-19, and — if there was no benefit — would there be harm?” lead author Mandeep R. Mehra, MD, MSc, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, said in an interview.
The investigators used data from a multinational registry comprising 671 hospitals that included patients (n = 96,032; mean age 53.8 years; 46.3% female) who had been hospitalized between Dec. 20, 2019, and April 14, 2020, with confirmed COVID-19 infection.
They also collected data about demographics, underlying comorbidities, and medical history, and medications that patients were taking at baseline.
Patients receiving treatment (n = 14,888) were divided into four groups: those receiving chloroquine alone (n = 1,868), those receiving chloroquine with a macrolide (n = 3,783), those receiving hydroxychloroquine alone (n = 3,016) and those receiving hydroxychloroquine with a macrolide (n = 6,221).
The remaining patients not treated with these regimens (n = 81,144) were regarded as the control group.
Most patients (65.9%) came from North America, followed by Europe (17.39%), Asia (7.9%), Africa (4.6%), South America (3.7%), and Australia (0.6%). Most (66.9%) were white, followed by patients of Asian origin (14.1%), black patients (9.4%), and Hispanic patients (6.2%).
Comorbidities and underlying conditions included obesity, hyperlipidemia, and hypertension in about 30%.
Comorbidities and underlying conditions
The investigators conducted multiple analyses to control for confounding variables, including Cox proportional hazards regression and propensity score matching analyses.
“In an observational study, there is always a chance of residual confounding, which is why we did propensity score based matched analyses,” Dr. Ruschitzka explained.
No significant differences were found in distribution of demographics and comorbidities between the groups.
As good as it gets
“We found no benefit in any of the four treatment regimens for hospitalized patients with COVID-19, but we did notice higher rates of death and serious ventricular arrhythmias in these patients, compared to the controls,” Dr. Mehra reported.
Of the patients in the control group, roughly 9.3% died during their hospitalization, compared with 16.4% of patients treated with chloroquine alone, 18.0% of those treated with hydroxychloroquine alone, 22.2% of those treated with chloroquine and a macrolide, and 23.8% of those treated with hydroxychloroquine and a macrolide.
After accounting for confounding variables, the researchers estimated that the excess mortality risk attributable to use of the drug regimen ranged from 34% to 45%.
Patients treated with any of the four regimens sustained more serious arrhythmias, compared with those in the control group (0.35), with the biggest increase seen in the group treated with the combination of hydroxychloroquine plus a macrolide (8.1%), followed by chloroquine with a macrolide (6.5%), hydroxychloroquine alone (6.1%), and chloroquine alone (4.3%).
“We were fairly reassured that, although the study was observational, the signals were robust and consistent across all regions of the world in diverse populations, and we did not see any muting of that signal, depending on region,” Dr. Mehra said.
“Two months ago, we were all scratching our heads about how to treat patients with COVID-19, and then came a drug [hydroxychloroquine] with some anecdotal evidence, but now we have 2 months more experience, and we looked to science to provide some answer,” Dr. Ruschitzka said.
“Although this was not a randomized, controlled trial, so we do not have a definite answer, the data provided in this [large, multinational] real-world study is as good as it gets and the best data we have,” he concluded.
“Let the science speak for itself”
Commenting on the study in an interview, Christian Funck-Brentano, MD, from the Hospital Pitié-Salpêtrière and Sorbonne University, both in Paris, said that, although the study is observational and therefore not as reliable as a randomized controlled trial, it is “nevertheless well-documented, studied a huge amount of people, and utilized several sensitivity methods, all of which showed the same results.”
Dr. Funck-Brentano, who is the coauthor of an accompanying editorial in The Lancet and was not involved with the study, said that “we now have no evidence that hydroxychloroquine and chloroquine alone or in combination with a macrolide do any good and we have potential evidence that they do harm and kill people.”
Also commenting on the study in an interview, David Holtgrave, PhD, dean of the School of Public Health at the State University of New York at Albany, said that, “while no one observational study alone would lead to a firm clinical recommendation, I think it is helpful for physicians and public health officials to be aware of the findings of the peer-reviewed observational studies to date and the National Institutes of Health COVID-19 treatment guidelines and the Food and Drug Administration’s statement of drug safety concern about hydroxychloroquine to inform their decision-making as we await the results of randomized clinical trials of these drugs for the treatment of COVID-19,” said Dr. Holtgrave, who was not involved with the study.
He added that, to his knowledge, there are “still no published studies of prophylactic use of these drugs to prevent COVID-19.”
Dr. Mehra emphasized that a cardinal principle of practicing medicine is “first do no harm” and “even in situations where you believe a desperate disease calls for desperate measures, responsible physicians should take a step back and ask if we are doing harm, and until we can say we aren’t, I don’t think it’s wise to push something like this in the absence of good efficacy data.”
Dr. Ruschitzka added that those who are encouraging the use of these agents “should review their decision based on today’s data and let the science speak for itself.”
The study was supported by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital, Boston. Dr. Mehra reported personal fees from Abbott, Medtronic, Janssen, Mesoblast, Portola, Bayer, Baim Institute for Clinical Research, NuPulseCV, FineHeart, Leviticus, Roivant, and Triple Gene. Dr. Ruschitzka was paid for time spent as a committee member for clinical trials, advisory boards, other forms of consulting, and lectures or presentations; these payments were made directly to the University of Zürich and no personal payments were received in relation to these trials or other activities. Dr. Funck-Brentano, his coauthor, and Dr. Holtgrave declared no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Hydroxychloroquine and chloroquine, with or without azithromycin or clarithromycin, offer no benefit in treating patients with COVID-19 and, instead, are associated with ventricular arrhythmias and higher rates of mortality, according to a major new international study.
In the largest observational study of its kind, including close to 100,000 people in 671 hospitals on six continents, investigators compared outcomes in 15,000 patients with COVID-19 treated with hydroxychloroquine and chloroquine alone or in combination with a macrolide with 80,000 control patients with COVID-19 not receiving these agents.
Treatment with any of these medications, either alone or in combination, was associated with increased death during hospitalization; compared with about 10% in control group patients, mortality rates ranged from more than 16% to almost 24% in the treated groups.
Patients treated with hydroxychloroquine plus a macrolide showed the highest rates of serious cardiac arrhythmias, and, even after accounting for demographic factors and comorbidities, this combination was found to be associated with a more than 5-fold increase in the risk of developing a serious arrhythmia while in the hospital.
“In this real-world study, the biggest yet, we looked at 100,000 patients [with COVID-19] across six continents and found not the slightest hint of benefits and only risks, and the data is pretty straightforward,” study coauthor Frank Ruschitzka, MD, director of the Heart Center at University Hospital, Zürich, said in an interview. The study was published online May 22 in The Lancet.
‘Inconclusive’ evidence
The absence of an effective treatment for COVID-19 has led to the “repurposing” of the antimalarial drug chloroquine and its analogue hydroxychloroquine, which is used for treating autoimmune disease, but this approach is based on anecdotal evidence or open-label randomized trials that have been “largely inconclusive,” the authors wrote.
Additional agents used to treat COVID-19 are second-generation macrolides (azithromycin or clarithromycin), in combination with chloroquine or hydroxychloroquine, “despite limited evidence” and the risk for ventricular arrhythmias, the authors noted.
“Our primary question was whether there was any associated benefits of the use of hydroxychloroquine, chloroquine, or a combined regimen with macrolides in treating COVID-19, and — if there was no benefit — would there be harm?” lead author Mandeep R. Mehra, MD, MSc, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, said in an interview.
The investigators used data from a multinational registry comprising 671 hospitals that included patients (n = 96,032; mean age 53.8 years; 46.3% female) who had been hospitalized between Dec. 20, 2019, and April 14, 2020, with confirmed COVID-19 infection.
They also collected data about demographics, underlying comorbidities, and medical history, and medications that patients were taking at baseline.
Patients receiving treatment (n = 14,888) were divided into four groups: those receiving chloroquine alone (n = 1,868), those receiving chloroquine with a macrolide (n = 3,783), those receiving hydroxychloroquine alone (n = 3,016) and those receiving hydroxychloroquine with a macrolide (n = 6,221).
The remaining patients not treated with these regimens (n = 81,144) were regarded as the control group.
Most patients (65.9%) came from North America, followed by Europe (17.39%), Asia (7.9%), Africa (4.6%), South America (3.7%), and Australia (0.6%). Most (66.9%) were white, followed by patients of Asian origin (14.1%), black patients (9.4%), and Hispanic patients (6.2%).
Comorbidities and underlying conditions included obesity, hyperlipidemia, and hypertension in about 30%.
Comorbidities and underlying conditions
The investigators conducted multiple analyses to control for confounding variables, including Cox proportional hazards regression and propensity score matching analyses.
“In an observational study, there is always a chance of residual confounding, which is why we did propensity score based matched analyses,” Dr. Ruschitzka explained.
No significant differences were found in distribution of demographics and comorbidities between the groups.
As good as it gets
“We found no benefit in any of the four treatment regimens for hospitalized patients with COVID-19, but we did notice higher rates of death and serious ventricular arrhythmias in these patients, compared to the controls,” Dr. Mehra reported.
Of the patients in the control group, roughly 9.3% died during their hospitalization, compared with 16.4% of patients treated with chloroquine alone, 18.0% of those treated with hydroxychloroquine alone, 22.2% of those treated with chloroquine and a macrolide, and 23.8% of those treated with hydroxychloroquine and a macrolide.
After accounting for confounding variables, the researchers estimated that the excess mortality risk attributable to use of the drug regimen ranged from 34% to 45%.
Patients treated with any of the four regimens sustained more serious arrhythmias, compared with those in the control group (0.35), with the biggest increase seen in the group treated with the combination of hydroxychloroquine plus a macrolide (8.1%), followed by chloroquine with a macrolide (6.5%), hydroxychloroquine alone (6.1%), and chloroquine alone (4.3%).
“We were fairly reassured that, although the study was observational, the signals were robust and consistent across all regions of the world in diverse populations, and we did not see any muting of that signal, depending on region,” Dr. Mehra said.
“Two months ago, we were all scratching our heads about how to treat patients with COVID-19, and then came a drug [hydroxychloroquine] with some anecdotal evidence, but now we have 2 months more experience, and we looked to science to provide some answer,” Dr. Ruschitzka said.
“Although this was not a randomized, controlled trial, so we do not have a definite answer, the data provided in this [large, multinational] real-world study is as good as it gets and the best data we have,” he concluded.
“Let the science speak for itself”
Commenting on the study in an interview, Christian Funck-Brentano, MD, from the Hospital Pitié-Salpêtrière and Sorbonne University, both in Paris, said that, although the study is observational and therefore not as reliable as a randomized controlled trial, it is “nevertheless well-documented, studied a huge amount of people, and utilized several sensitivity methods, all of which showed the same results.”
Dr. Funck-Brentano, who is the coauthor of an accompanying editorial in The Lancet and was not involved with the study, said that “we now have no evidence that hydroxychloroquine and chloroquine alone or in combination with a macrolide do any good and we have potential evidence that they do harm and kill people.”
Also commenting on the study in an interview, David Holtgrave, PhD, dean of the School of Public Health at the State University of New York at Albany, said that, “while no one observational study alone would lead to a firm clinical recommendation, I think it is helpful for physicians and public health officials to be aware of the findings of the peer-reviewed observational studies to date and the National Institutes of Health COVID-19 treatment guidelines and the Food and Drug Administration’s statement of drug safety concern about hydroxychloroquine to inform their decision-making as we await the results of randomized clinical trials of these drugs for the treatment of COVID-19,” said Dr. Holtgrave, who was not involved with the study.
He added that, to his knowledge, there are “still no published studies of prophylactic use of these drugs to prevent COVID-19.”
Dr. Mehra emphasized that a cardinal principle of practicing medicine is “first do no harm” and “even in situations where you believe a desperate disease calls for desperate measures, responsible physicians should take a step back and ask if we are doing harm, and until we can say we aren’t, I don’t think it’s wise to push something like this in the absence of good efficacy data.”
Dr. Ruschitzka added that those who are encouraging the use of these agents “should review their decision based on today’s data and let the science speak for itself.”
The study was supported by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital, Boston. Dr. Mehra reported personal fees from Abbott, Medtronic, Janssen, Mesoblast, Portola, Bayer, Baim Institute for Clinical Research, NuPulseCV, FineHeart, Leviticus, Roivant, and Triple Gene. Dr. Ruschitzka was paid for time spent as a committee member for clinical trials, advisory boards, other forms of consulting, and lectures or presentations; these payments were made directly to the University of Zürich and no personal payments were received in relation to these trials or other activities. Dr. Funck-Brentano, his coauthor, and Dr. Holtgrave declared no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Immunotherapy, steroids had positive outcomes in COVID-19–associated multisystem inflammatory syndrome
According to study of a cluster of patients in France and Switzerland, children may experience an acute cardiac decompensation from the severe inflammatory state following SARS-CoV-2 infection, termed multisystem inflammatory syndrome in children (MIS-C). Treatment with immunoglobulin appears to be associated with recovery of left ventricular systolic function.
“The pediatric and cardiology communities should be acutely aware of this new disease probably related to SARS-CoV-2 infection (MIS-C), that shares similarities with Kawasaki disease but has specificities in its presentation,” researchers led by Zahra Belhadjer, MD, of Necker-Enfants Malades Hospital in Paris, wrote in a cases series report published online in Circulation “Early diagnosis and management appear to lead to favorable outcome using classical therapies. Elucidating the immune mechanisms of this disease will afford further insights for treatment and potential global prevention of severe forms.”
Over a 2-month period that coincided with the SARS-CoV-2 pandemic in France and Switzerland, the researchers retrospectively collected clinical, biological, therapeutic, and early-outcomes data in 35 children who were admitted to pediatric ICUs in 14 centers for cardiogenic shock, left ventricular dysfunction, and severe inflammatory state. Their median age was 10 years, all presented with a fever, 80% had gastrointestinal symptoms of abdominal pain, vomiting, or diarrhea, and 28% had comorbidities that included body mass index of greater than 25 kg/m2 (17%), asthma (9%), and lupus (3%), and overweight. Only 17% presented with chest pain. The researchers observed that left ventricular ejection fraction was less than 30% in 28% of patients, and 80% required inotropic support with 28% treated with extracorporeal membrane oxygenation (ECMO). All patients presented with a severe inflammatory state evidenced by elevated C-reactive protein and d-dimer. Interleukin 6 was elevated to a median of 135 pg/mL in 13 of the patients. Elevation of troponin I was constant but mild to moderate, and NT-proBNP or BNP elevation was present in all children.
Nearly all patients 35 (88%) patients tested positive for SARS-CoV-2 infection by polymerase chain reaction of nasopharyngeal swab or serology. Most patients (80%) received IV inotropic support, 71% received first-line IV immunoglobulin, 65% received anticoagulation with heparin, 34% received IV steroids having been considered high-risk patients with symptoms similar to an incomplete form of Kawasaki disease, and 8% received treatment with an interleukin-1 receptor antagonist because of a persistent severe inflammatory state. Left ventricular function was restored in 71% of those discharged from the intensive care unit. No patient died, and all patients treated with ECMO were successfully weaned after a median of 4.5 days.
“Some aspects of this emerging pediatric disease (MIS-C) are similar to those of Kawasaki disease: prolonged fever, multisystem inflammation with skin rash, lymphadenopathy, diarrhea, meningism, and high levels of inflammatory biomarkers,” the researchers wrote. “But differences are important and raise the question as to whether this syndrome is Kawasaki disease with SARS-CoV-2 as the triggering agent, or represents a different syndrome (MIS-C). Kawasaki disease predominantly affects young children younger than 5 years, whereas the median age in our series is 10 years. Incomplete forms of Kawasaki disease occur in infants who may have fever as the sole clinical finding, whereas older patients are more prone to exhibit the complete form.”
They went on to note that the overlapping features between MIS-C and Kawasaki disease “may be due to similar pathophysiology. The etiologic agent of Kawasaki disease is unknown but likely to be ubiquitous, causing asymptomatic childhood infection but triggering the immunologic cascade of Kawasaki disease in genetically susceptible individuals. Please note that infection with a novel RNA virus that enters through the upper respiratory tract has been proposed to be the cause of the disease (see PLoS One. 2008 Feb 13;3:e1582 and J Infect Dis. 2011 Apr 1;203:1021-30).”
Based on the work of authors, it appears that a high index of suspicion for MIS-C is important for children who develop Kawasaki-like symptoms, David J. Goldberg, MD, said in an interview. “Although children have largely been spared from the acute respiratory presentation of the SARS-CoV-2 pandemic, the recognition and understanding of what appears to be a postviral inflammatory response is a critical first step in developing treatment algorithms for this disease process,” said Dr. Goldberg, a board-certified attending cardiologist in the cardiac center and fetal heart program at Children’s Hospital of Philadelphia. “If inflammatory markers are elevated, particularly if there are accompanying gastrointestinal symptoms, the possibility of cardiac involvement suggests the utility of screening echocardiography. Given the potential need for inotropic or mechanical circulatory support, the presence of myocardial dysfunction dictates care in an intensive care unit capable of providing advanced therapies. While the evidence from Dr. Belhadjer’s cohort suggests that full recovery is probable, there is still much to be learned about this unique inflammatory syndrome and the alarm has rightly been sounded.”
The researchers and Dr. Goldberg reported having no disclosures.
SOURCE: Belhadjer Z et al. Circulation 2020 May 17; doi: 10.1161/circulationaha.120.048360.
According to study of a cluster of patients in France and Switzerland, children may experience an acute cardiac decompensation from the severe inflammatory state following SARS-CoV-2 infection, termed multisystem inflammatory syndrome in children (MIS-C). Treatment with immunoglobulin appears to be associated with recovery of left ventricular systolic function.
“The pediatric and cardiology communities should be acutely aware of this new disease probably related to SARS-CoV-2 infection (MIS-C), that shares similarities with Kawasaki disease but has specificities in its presentation,” researchers led by Zahra Belhadjer, MD, of Necker-Enfants Malades Hospital in Paris, wrote in a cases series report published online in Circulation “Early diagnosis and management appear to lead to favorable outcome using classical therapies. Elucidating the immune mechanisms of this disease will afford further insights for treatment and potential global prevention of severe forms.”
Over a 2-month period that coincided with the SARS-CoV-2 pandemic in France and Switzerland, the researchers retrospectively collected clinical, biological, therapeutic, and early-outcomes data in 35 children who were admitted to pediatric ICUs in 14 centers for cardiogenic shock, left ventricular dysfunction, and severe inflammatory state. Their median age was 10 years, all presented with a fever, 80% had gastrointestinal symptoms of abdominal pain, vomiting, or diarrhea, and 28% had comorbidities that included body mass index of greater than 25 kg/m2 (17%), asthma (9%), and lupus (3%), and overweight. Only 17% presented with chest pain. The researchers observed that left ventricular ejection fraction was less than 30% in 28% of patients, and 80% required inotropic support with 28% treated with extracorporeal membrane oxygenation (ECMO). All patients presented with a severe inflammatory state evidenced by elevated C-reactive protein and d-dimer. Interleukin 6 was elevated to a median of 135 pg/mL in 13 of the patients. Elevation of troponin I was constant but mild to moderate, and NT-proBNP or BNP elevation was present in all children.
Nearly all patients 35 (88%) patients tested positive for SARS-CoV-2 infection by polymerase chain reaction of nasopharyngeal swab or serology. Most patients (80%) received IV inotropic support, 71% received first-line IV immunoglobulin, 65% received anticoagulation with heparin, 34% received IV steroids having been considered high-risk patients with symptoms similar to an incomplete form of Kawasaki disease, and 8% received treatment with an interleukin-1 receptor antagonist because of a persistent severe inflammatory state. Left ventricular function was restored in 71% of those discharged from the intensive care unit. No patient died, and all patients treated with ECMO were successfully weaned after a median of 4.5 days.
“Some aspects of this emerging pediatric disease (MIS-C) are similar to those of Kawasaki disease: prolonged fever, multisystem inflammation with skin rash, lymphadenopathy, diarrhea, meningism, and high levels of inflammatory biomarkers,” the researchers wrote. “But differences are important and raise the question as to whether this syndrome is Kawasaki disease with SARS-CoV-2 as the triggering agent, or represents a different syndrome (MIS-C). Kawasaki disease predominantly affects young children younger than 5 years, whereas the median age in our series is 10 years. Incomplete forms of Kawasaki disease occur in infants who may have fever as the sole clinical finding, whereas older patients are more prone to exhibit the complete form.”
They went on to note that the overlapping features between MIS-C and Kawasaki disease “may be due to similar pathophysiology. The etiologic agent of Kawasaki disease is unknown but likely to be ubiquitous, causing asymptomatic childhood infection but triggering the immunologic cascade of Kawasaki disease in genetically susceptible individuals. Please note that infection with a novel RNA virus that enters through the upper respiratory tract has been proposed to be the cause of the disease (see PLoS One. 2008 Feb 13;3:e1582 and J Infect Dis. 2011 Apr 1;203:1021-30).”
Based on the work of authors, it appears that a high index of suspicion for MIS-C is important for children who develop Kawasaki-like symptoms, David J. Goldberg, MD, said in an interview. “Although children have largely been spared from the acute respiratory presentation of the SARS-CoV-2 pandemic, the recognition and understanding of what appears to be a postviral inflammatory response is a critical first step in developing treatment algorithms for this disease process,” said Dr. Goldberg, a board-certified attending cardiologist in the cardiac center and fetal heart program at Children’s Hospital of Philadelphia. “If inflammatory markers are elevated, particularly if there are accompanying gastrointestinal symptoms, the possibility of cardiac involvement suggests the utility of screening echocardiography. Given the potential need for inotropic or mechanical circulatory support, the presence of myocardial dysfunction dictates care in an intensive care unit capable of providing advanced therapies. While the evidence from Dr. Belhadjer’s cohort suggests that full recovery is probable, there is still much to be learned about this unique inflammatory syndrome and the alarm has rightly been sounded.”
The researchers and Dr. Goldberg reported having no disclosures.
SOURCE: Belhadjer Z et al. Circulation 2020 May 17; doi: 10.1161/circulationaha.120.048360.
According to study of a cluster of patients in France and Switzerland, children may experience an acute cardiac decompensation from the severe inflammatory state following SARS-CoV-2 infection, termed multisystem inflammatory syndrome in children (MIS-C). Treatment with immunoglobulin appears to be associated with recovery of left ventricular systolic function.
“The pediatric and cardiology communities should be acutely aware of this new disease probably related to SARS-CoV-2 infection (MIS-C), that shares similarities with Kawasaki disease but has specificities in its presentation,” researchers led by Zahra Belhadjer, MD, of Necker-Enfants Malades Hospital in Paris, wrote in a cases series report published online in Circulation “Early diagnosis and management appear to lead to favorable outcome using classical therapies. Elucidating the immune mechanisms of this disease will afford further insights for treatment and potential global prevention of severe forms.”
Over a 2-month period that coincided with the SARS-CoV-2 pandemic in France and Switzerland, the researchers retrospectively collected clinical, biological, therapeutic, and early-outcomes data in 35 children who were admitted to pediatric ICUs in 14 centers for cardiogenic shock, left ventricular dysfunction, and severe inflammatory state. Their median age was 10 years, all presented with a fever, 80% had gastrointestinal symptoms of abdominal pain, vomiting, or diarrhea, and 28% had comorbidities that included body mass index of greater than 25 kg/m2 (17%), asthma (9%), and lupus (3%), and overweight. Only 17% presented with chest pain. The researchers observed that left ventricular ejection fraction was less than 30% in 28% of patients, and 80% required inotropic support with 28% treated with extracorporeal membrane oxygenation (ECMO). All patients presented with a severe inflammatory state evidenced by elevated C-reactive protein and d-dimer. Interleukin 6 was elevated to a median of 135 pg/mL in 13 of the patients. Elevation of troponin I was constant but mild to moderate, and NT-proBNP or BNP elevation was present in all children.
Nearly all patients 35 (88%) patients tested positive for SARS-CoV-2 infection by polymerase chain reaction of nasopharyngeal swab or serology. Most patients (80%) received IV inotropic support, 71% received first-line IV immunoglobulin, 65% received anticoagulation with heparin, 34% received IV steroids having been considered high-risk patients with symptoms similar to an incomplete form of Kawasaki disease, and 8% received treatment with an interleukin-1 receptor antagonist because of a persistent severe inflammatory state. Left ventricular function was restored in 71% of those discharged from the intensive care unit. No patient died, and all patients treated with ECMO were successfully weaned after a median of 4.5 days.
“Some aspects of this emerging pediatric disease (MIS-C) are similar to those of Kawasaki disease: prolonged fever, multisystem inflammation with skin rash, lymphadenopathy, diarrhea, meningism, and high levels of inflammatory biomarkers,” the researchers wrote. “But differences are important and raise the question as to whether this syndrome is Kawasaki disease with SARS-CoV-2 as the triggering agent, or represents a different syndrome (MIS-C). Kawasaki disease predominantly affects young children younger than 5 years, whereas the median age in our series is 10 years. Incomplete forms of Kawasaki disease occur in infants who may have fever as the sole clinical finding, whereas older patients are more prone to exhibit the complete form.”
They went on to note that the overlapping features between MIS-C and Kawasaki disease “may be due to similar pathophysiology. The etiologic agent of Kawasaki disease is unknown but likely to be ubiquitous, causing asymptomatic childhood infection but triggering the immunologic cascade of Kawasaki disease in genetically susceptible individuals. Please note that infection with a novel RNA virus that enters through the upper respiratory tract has been proposed to be the cause of the disease (see PLoS One. 2008 Feb 13;3:e1582 and J Infect Dis. 2011 Apr 1;203:1021-30).”
Based on the work of authors, it appears that a high index of suspicion for MIS-C is important for children who develop Kawasaki-like symptoms, David J. Goldberg, MD, said in an interview. “Although children have largely been spared from the acute respiratory presentation of the SARS-CoV-2 pandemic, the recognition and understanding of what appears to be a postviral inflammatory response is a critical first step in developing treatment algorithms for this disease process,” said Dr. Goldberg, a board-certified attending cardiologist in the cardiac center and fetal heart program at Children’s Hospital of Philadelphia. “If inflammatory markers are elevated, particularly if there are accompanying gastrointestinal symptoms, the possibility of cardiac involvement suggests the utility of screening echocardiography. Given the potential need for inotropic or mechanical circulatory support, the presence of myocardial dysfunction dictates care in an intensive care unit capable of providing advanced therapies. While the evidence from Dr. Belhadjer’s cohort suggests that full recovery is probable, there is still much to be learned about this unique inflammatory syndrome and the alarm has rightly been sounded.”
The researchers and Dr. Goldberg reported having no disclosures.
SOURCE: Belhadjer Z et al. Circulation 2020 May 17; doi: 10.1161/circulationaha.120.048360.
FROM CIRCULATION
Newer anticoagulants linked to lower fracture risk in AFib
The direct oral anticoagulant (DOAC) drugs apixaban, dabigatran, and rivaroxaban are associated with a lower risk of osteoporotic fracture than is warfarin in patients with atrial fibrillation (AFib), according to a new retrospective analysis.
There was no difference in risk between individual DOAC medications.
The study drew from an EHR database of the Hong Kong Hospital Authority. It was led by Wallis C.Y. Lau, PhD, of the University of Hong Kong and appeared online May 19 in Annals of Internal Medicine.
Warfarin is suspected to contribute to osteoporotic fracturing in AFib patients, but previous studies returned mixed results. The more recently introduced DOACs were not tested for fracture risks, and it hasn’t been determined if individual DOACs have different risks. The question is even more important in AFib, in which patients are older and often have comorbidities that could predispose them to fractures.
The study included 23,515 patients with AFib who used anticoagulants. 3,241 used apixaban, 6,867 dabigatran, 3,866 rivaroxaban, and 9,541 used warfarin. The median follow-up was 423 days.
According to Cox proportional hazards model analyses, DOAC use was associated with fewer fractures than was warfarin (hazard ratio for apixaban vs. warfarin, 0.62; 95% confidence interval, 0.41-0.94; HR for dabigatran, 0.65; 95% CI, 0.49-0.86; HR for rivaroxaban, 0.52; 95% CI, 0.37-0.73). Subanalyses in men and women showed similar results (P for interaction >.05).
Head-to-head comparisons between individual DOACs yielded no statistically significant differences in osteoporotic fracture risk.
Although the findings couldn’t absolutely rule out a difference in osteoporotic fracture risk between different DOACs, the authors argue that any clinical significance would likely be small.
“Given the supportive evidence from experimental settings, findings from our study using clinical data, and the indirect evidence provided by the previous meta-analysis of randomized, controlled trials, there exists a compelling case for evaluating whether the risk for osteoporotic fractures should be considered at the point of prescribing an oral anticoagulant to minimize fracture risk,” the authors wrote.
The study is limited by the potential for residual confounding, the investigators noted.
The study was funded by the University of Hong Kong and University College London Strategic Partnership Fund.
SOURCE: Lau WCY et al. Ann Intern Med. 2020 May 19. doi: 10.7326/M19-3671.
The direct oral anticoagulant (DOAC) drugs apixaban, dabigatran, and rivaroxaban are associated with a lower risk of osteoporotic fracture than is warfarin in patients with atrial fibrillation (AFib), according to a new retrospective analysis.
There was no difference in risk between individual DOAC medications.
The study drew from an EHR database of the Hong Kong Hospital Authority. It was led by Wallis C.Y. Lau, PhD, of the University of Hong Kong and appeared online May 19 in Annals of Internal Medicine.
Warfarin is suspected to contribute to osteoporotic fracturing in AFib patients, but previous studies returned mixed results. The more recently introduced DOACs were not tested for fracture risks, and it hasn’t been determined if individual DOACs have different risks. The question is even more important in AFib, in which patients are older and often have comorbidities that could predispose them to fractures.
The study included 23,515 patients with AFib who used anticoagulants. 3,241 used apixaban, 6,867 dabigatran, 3,866 rivaroxaban, and 9,541 used warfarin. The median follow-up was 423 days.
According to Cox proportional hazards model analyses, DOAC use was associated with fewer fractures than was warfarin (hazard ratio for apixaban vs. warfarin, 0.62; 95% confidence interval, 0.41-0.94; HR for dabigatran, 0.65; 95% CI, 0.49-0.86; HR for rivaroxaban, 0.52; 95% CI, 0.37-0.73). Subanalyses in men and women showed similar results (P for interaction >.05).
Head-to-head comparisons between individual DOACs yielded no statistically significant differences in osteoporotic fracture risk.
Although the findings couldn’t absolutely rule out a difference in osteoporotic fracture risk between different DOACs, the authors argue that any clinical significance would likely be small.
“Given the supportive evidence from experimental settings, findings from our study using clinical data, and the indirect evidence provided by the previous meta-analysis of randomized, controlled trials, there exists a compelling case for evaluating whether the risk for osteoporotic fractures should be considered at the point of prescribing an oral anticoagulant to minimize fracture risk,” the authors wrote.
The study is limited by the potential for residual confounding, the investigators noted.
The study was funded by the University of Hong Kong and University College London Strategic Partnership Fund.
SOURCE: Lau WCY et al. Ann Intern Med. 2020 May 19. doi: 10.7326/M19-3671.
The direct oral anticoagulant (DOAC) drugs apixaban, dabigatran, and rivaroxaban are associated with a lower risk of osteoporotic fracture than is warfarin in patients with atrial fibrillation (AFib), according to a new retrospective analysis.
There was no difference in risk between individual DOAC medications.
The study drew from an EHR database of the Hong Kong Hospital Authority. It was led by Wallis C.Y. Lau, PhD, of the University of Hong Kong and appeared online May 19 in Annals of Internal Medicine.
Warfarin is suspected to contribute to osteoporotic fracturing in AFib patients, but previous studies returned mixed results. The more recently introduced DOACs were not tested for fracture risks, and it hasn’t been determined if individual DOACs have different risks. The question is even more important in AFib, in which patients are older and often have comorbidities that could predispose them to fractures.
The study included 23,515 patients with AFib who used anticoagulants. 3,241 used apixaban, 6,867 dabigatran, 3,866 rivaroxaban, and 9,541 used warfarin. The median follow-up was 423 days.
According to Cox proportional hazards model analyses, DOAC use was associated with fewer fractures than was warfarin (hazard ratio for apixaban vs. warfarin, 0.62; 95% confidence interval, 0.41-0.94; HR for dabigatran, 0.65; 95% CI, 0.49-0.86; HR for rivaroxaban, 0.52; 95% CI, 0.37-0.73). Subanalyses in men and women showed similar results (P for interaction >.05).
Head-to-head comparisons between individual DOACs yielded no statistically significant differences in osteoporotic fracture risk.
Although the findings couldn’t absolutely rule out a difference in osteoporotic fracture risk between different DOACs, the authors argue that any clinical significance would likely be small.
“Given the supportive evidence from experimental settings, findings from our study using clinical data, and the indirect evidence provided by the previous meta-analysis of randomized, controlled trials, there exists a compelling case for evaluating whether the risk for osteoporotic fractures should be considered at the point of prescribing an oral anticoagulant to minimize fracture risk,” the authors wrote.
The study is limited by the potential for residual confounding, the investigators noted.
The study was funded by the University of Hong Kong and University College London Strategic Partnership Fund.
SOURCE: Lau WCY et al. Ann Intern Med. 2020 May 19. doi: 10.7326/M19-3671.
FROM ANNALS OF INTERNAL MEDICINE
Team-Based Hypertension Management in Outpatient Settings
From Western University of Health Sciences College of Pharmacy, Department of Pharmacy Practice and Administration, Pomona, CA.
Abstract
- Objective: To review the current literature regarding the clinical effectiveness and cost-effectiveness of implementing hypertension team-based care (TBC) interventions in the outpatient setting, and discuss challenges to implementation.
- Methods: A literature review was conducted of meta-analyses, systematic reviews, and randomized controlled trials comparing TBC models to usual care for hypertension management.
- Results: Compared to usual care, TBC models have demonstrated greater blood pressure reductions and improved blood pressure control rates. Evidence was strongest for models involving nurses and pharmacists whose roles included medication management, patient education and counseling, coordination of care and follow-up, population health management, and performance measurement with quality improvement. Although TBC results in an increase in health care costs, the overall long-term benefits support the cost-effectiveness of these models over usual care. The most common barriers to TBC implementation include underutilization of technology, stakeholder engagement, and reimbursement issues.
- Conclusion: Hypertension TBC models have been shown to be clinically effective and cost-effective, but continued research comparing different models is warranted to determine which combination of health professionals and interventions is most impactful and cost-effective in practice. An implementation science approach, in which TBC models unique to each organization’s situation are created, will be useful to identify and overcome challenges and provide a solid foundation for sustainment.
Keywords: blood pressure; pharmacist; nurse; nurse practitioner; cost-effectiveness; team-based care.
Approximately 1 in 3 US adults—or about 100 million people—have high blood pressure, and only about half (48%) have their blood pressure under control.1 Effective blood pressure management has been shown to decrease the incidence of stroke, heart attack, and heart failure.2-4 The American College of Cardiology/American Heart Association (ACC/AHA) 2017 blood pressure guidelines recommended lower thresholds for diagnosing hypertension and initiating antihypertensive medication, and intensified the blood pressure goal to less than 130/80 mm Hg.5 Changing practice standards to more intensive blood pressure goals requires significant adjustments by clinicians and health care systems. In fact, new guideline uptake is often delayed, ignored, or sparsely applied.6 Due to this dramatic change in hypertension practice standards, the ACC/AHA guidelines support interdisciplinary team-based care (TBC) for hypertension management.5,7 Additionally, the Centers for Disease Control and Prevention (CDC) and the Community Preventive Services Task Force (CPSTF) promote TBC to improve blood pressure control in their initiatives to prevent heart disease and stroke.8,9
The National Academy of Medicine defines TBC as “the provision of health services to individuals, families, and/or their communities by at least 2 healthcare providers who work collaboratively with patients and their caregivers—to the extent preferred by each patient—to accomplish shared goals within and across settings to achieve coordinated, high-quality care.”10 Specific goals for TBC in hypertension treatment are listed in Table 1, and a checklist of key elements of TBC to consider before implementation are presented in Table 2.
TBC has been shown to have many advantages, including increased access to care due to expanded hours of operation and shorter wait times.11 Team-based models also provide effective and efficient delivery of patient education, behavioral health care, and care coordination.12-14 Patients are more likely to receive high-quality care when multiple providers, each with varied expertise, are on the health care team.11,15 Furthermore, clinicians report improved professional job satisfaction related to their ability to practice in environments where they are encouraged to work at the top of their licenses.16 Consequently, TBC has been accepted as a vital part of the patient-centered medical home (PCMH) model.17-19 Standards set by the National Committee for Quality Assurance (NCQA) include TBC as a requirement health systems must meet in order to achieve the highest level of PCMH recognition. While a team-based approach offers substantial benefits and is recognized as a marker of quality, implementation has presented various challenges, and the sustainability of these models in care settings has been questioned.20
In this article, we review the current literature regarding the clinical effectiveness and cost-effectiveness of implementing hypertension TBC interventions in the outpatient setting. We also discuss the challenges and opportunities of implementing this strategy in health systems and community settings in the United States.
Evidence of Impact and Effectiveness
Various models of hypertension TBC have been shown to increase the proportion of individuals with controlled blood pressure and to lead to a reduction in both systolic (SBP) and diastolic blood pressure (DBP), resulting in a strong recommendation for TBC approaches by the 2017 ACC/AHA blood pressure guidelines.5,21-25 There is great diversity in the types of hypertension treatment models studied, with few utilizing physician specialists and most utilizing nonphysician providers, such as community health workers, physician assistants, nurses, nurse practitioners, dietitians, social workers, and pharmacists.22,26-29 These professionals share duties of hypertension management with primary care physicians to reduce the burden of responsibility for care on any single provider type. TBC is patient-centered, and typically includes interprofessional collaboration, treatment algorithms, adherence counseling, frequent follow-up, home blood pressure monitoring, and patient self-management education.
Numerous studies have supported implementation of TBC in recent years. A systematic review and meta-analysis of 100 trials of hypertension TBC involving 55,920 patients concluded that the most effective blood pressure–lowering strategies use multilevel, multicomponent approaches to address barriers to hypertension control. Nonphysician providers are often involved in measuring blood pressure, ordering and assessing laboratory tests, and titrating medications.30 Compared with usual care, TBC with physician medication titration resulted in reductions in mean SBP and DBP (6.2 mm Hg and 2.7 mm Hg, respectively), while TBC with nonphysician medication titration also resulted in reductions in mean SBP and DBP (7.1 mm Hg and 3.1 mm Hg, respectively). Nurses and pharmacists are specifically mentioned by the 2017 ACC/AHA blood pressure guidelines as essential members of the hypertension treatment team.5 Randomized controlled trials (RCTs) and meta-analyses of TBC involving nurse or pharmacist interventions demonstrated greater reductions in SBP and/or greater attainment of blood pressure goals compared to usual care.21,26,31,32 The literature supports the roles of nurses and pharmacists in hypertension management in all aspects of care, including medication management, patient education and counseling, coordination of care and follow-up, population health management, and performance measurement with quality improvement.33
Nurses
Nurses are commonly part of TBC hypertension management programs. One meta-analysis and systematic review of international RCTs compared nurse, nurse prescriber (United Kingdom), and nurse practitioner interventions for hypertension with usual care. Interventions that included a stepped treatment algorithm and nurse prescribing showed greater reductions in SBP (8.2 mm Hg and 8.9 mm Hg, respectively) compared to usual care.31 Similarly, models that utilized telephone monitoring demonstrated greater achievement of blood pressure targets, while those that involved home monitoring showed significant reductions in blood pressure. Another international meta-analysis and systematic review of 11 nurse-led interventions in hypertensive patients with diabetes demonstrated a 5.8 mm Hg mean decrease in SBP compared to physician-led care. However, nurse-led care was not superior in achievement of study targets.34
A recent meta-analysis and systematic review, performed by Shaw and colleagues, sought to determine whether nurse-led protocols are effective for outpatient management of adults with diabetes, hypertension, and hyperlipidemia. All of the included studies involved a registered nurse who titrated medications by following a protocol, and most were RCTs comparing the nurse protocols to usual care. Overall, mean SBP and DBP decreased by 3.86 mm Hg and 1.56 mm Hg, respectively, while blood glucose and lipid levels were also reduced compared to usual care.24
Limited RCT data have been published since the Shaw et al meta-analysis. A single-blind RCT was performed in an urban community health care center in China among patients with uncontrolled blood pressure (SBP ≥ 140 mm Hg and/or DBP ≥ 90 mm Hg).35 The study group received care via a nurse-led model, which included a delivery design system, decision support, clinical information system, and self-management support, and the control group received usual care. At 12 weeks, patients in the study group had significantly lower blood pressure than control patients, with mean SBP/DBP reduction of 14.37/7.43 mm Hg and 5.10/2.69 mm Hg, respectively (P < 0.01). Improved medication adherence and increased patient satisfaction were other benefits of the nurse-led model.
Nurse case managers (NCM) also play a critical role in hypertension management, coordinating health care services to meet patient health needs. Ogedegbe sought to evaluate the comparative effectiveness of home blood pressure telemonitoring (HBPTM)+NCM versus HBPTM alone on SBP reduction in black and Hispanic stroke survivors.36,37 NCMs evaluated patient profiles, counseled patients on target lifestyle behaviors, and reviewed home blood pressure data. At 6 months, SBP declined by 13.63 mm Hg from baseline in the HBPTM+NCM group and 6.31 mm Hg in the HBPTM alone group (P < 0.0001). At 12 months, SBP in the HBPTM+NCM group declined by 14.76 mm Hg, while blood pressure in the HBPTM alone group declined by 5.53 mm Hg (P < 0.0001).
Pharmacists
Clinical pharmacists are also widely utilized in TBC models for hypertension management. Typical models involve pharmacists entering into collaborative practice agreements with physicians, leading to optimization of medications, avoidance of adverse drug events, and transitional care activities focusing on medication reconciliation and patient education in outpatient settings.30,38 The largest and most recent meta-analysis of pharmacist interventions, conducted in 2014 by Santschi et al,23 combined 2 previous systematic reviews to include a total of 39 RCTs with 14,224 patients.32,39 Pharmacist interventions included patient education, recommendations to physicians, and medication management. Compared with usual care, pharmacist interventions showed greater reductions in SBP (7.6 mm Hg) and DBP (3.9 mm Hg).23
Numerous studies substantiating the impact of pharmacist interventions on clinical outcomes have heavily influenced clinical practice and guideline development. Carter et al conducted a prospective, multi-state, cluster-randomized trial in 32 primary care clinics to evaluate whether clinics randomized to receive the pharmacist-physician collaborative care model (PPCCM) achieved better blood pressure outcomes versus clinics randomized to usual care.25 Investigators enrolled 625 patients with uncontrolled hypertension, 50% of whom had a prior diagnosis of diabetes mellitus or chronic kidney disease. The primary outcome of blood pressure control at 9 months in the intervention clinics compared to the control clinics was 43% and 34%, respectively (P = 0.059). The difference in mean SBP/DBP between the intervention and control clinics for all patients at 9 months was −6.1/−2.9 mm Hg. In a post-hoc analysis of patients with chronic kidney disease and diabetes, the pharmacist-intervention group had a significantly greater mean SBP reduction and higher blood pressure control rates compared to usual care at 9 months.40
A pre-specified secondary analysis from the Carter et al study determined that, in patients from racial minority groups, the mean SBP was 7.3 mm Hg lower in those who received the intervention compared to those in the control group (P = 0.0042).41 In patients with less than 12 years of education, those in the intervention group had a mean SBP 8.1 mm Hg lower than the SBP of those in the control group (P = 0.0001). Similar reductions in blood pressure occurred in patients with low income, Medicaid beneficiaries, or those without insurance. This study demonstrated that pharmacist interventions reduced racial and socioeconomic disparities in blood pressure treatment.
Other studies of pharmacist interventions in underserved populations have yielded positive results. In a retrospective review of uninsured patients, blood pressure control rates in a pharmacist-driven primary care clinic ranked in the 90th percentile of NCQA benchmarks, and was superior to the 2013 reported mean for commercial insurers.42 Similarly, another retrospective cohort study of a PPCCM on time to goal blood pressure in uninsured patients with hypertension showed the median time to blood pressure goal was 36 days in the PPCCM cohort versus 259 days in usual care cohorts (P < 0.001).43 A post-hoc analysis revealed the mean time-in-therapeutic blood pressure range was 46.2% ± 24.3% in the PPCCM group and 24.8% ± 27.4% in the usual care group (P < 0.0001). The blood pressure control rates at 12 months were 89% in the PPCCM group compared with 50% in the usual care group (P < 0.0001).44
Tsuyuki et al conducted the RxACTION study, a multicenter RCT evaluating the effectiveness of enhanced pharmacist care versus usual care in 23 Canadian community pharmacies and outpatient clinics following a 6-month intervention.45 Enhanced pharmacy services included pharmacist assessment of and counseling about cardiovascular disease risk and blood pressure control, review of current antihypertensive medications, and prescribing/titrating drug therapy, as needed, through independent prescriptive authority. Compared to the usual care group (n = 67), the intervention group had a reduction in SBP of 6.6 mm Hg (P = 0.006) and in DBP of 3.2 mm Hg (P = 0.01). This study expanded the pharmacists’ scope of practice, showing evidence for enhancing pharmacist roles on the hypertension care team. Tsuyuki et al also conducted the RxEACH randomized trial, which evaluated community pharmacist cardiovascular risk reduction interventions and showed an improvement in SBP and DBP, with reported results comparable to RxACTION.46
Victor et al conducted the landmark Black Barbershop Study, a cluster RCT involving 319 non-Hispanic black male patients with hypertension from 52 black-owned barbershops.47,48 Barbershops were assigned to 1 of 2 groups. The control group consisted of barbers who encouraged lifestyle modifications and made referrals to primary care providers. The intervention group had pharmacists who met regularly with participants at the barbershops and measured blood pressure, encouraged lifestyle changes, and prescribed drug therapy under collaborative practice agreements with physicians. Both groups demonstrated improvements in blood pressure outcomes, but the intervention group showed greater improvement in SBP and achievement of blood pressure goals compared to the control group. The results in the intervention group proved sustainable over the course of a year, even after the frequency of pharmacists’ visits was reduced. At 6 months, the mean SBP fell by 27.0 mm Hg (to 125.8 mm Hg) in the intervention group, as compared to a 9.3 mm Hg (to 145.4 mm Hg) reduction in the control group (P < 0.001), and blood pressure less than 130/80 mm Hg was achieved among 63.6% of the participants in the intervention group versus 11.7% in the control group (P < 0.001).
This community-level trial brought pharmacists to the barbershop and made them an essential part of the health care team through the endorsement of the barber, who the participants trusted and with whom they had a relationship. Long-standing issues related to distrust of the medical profession by this population were addressed, and trusted community barbershops were utilized as safe spaces for health care delivery. Health care professionals should consider utilizing community locations that other minority populations perceive as social centers and safe places, to reduce health disparities and barriers to care. However, models that bring care to patients need further economic and feasibility evaluations.
Other Health Care Professionals and Future Studies
In addition to models led by nurses and pharmacists, studies have also assessed models of TBC incorporating other health care professionals, including registered dietitians, medical assistants, community health workers, and health coaches (NCT02674464).49,50 Ongoing studies are also looking at the impact of TBC on underserved communities (NCT02674464, NCT03504124). Involving a variety of health care professionals with different communities and populations in TBC studies is warranted to determine the optimal settings in which to utilize different skill sets.
The Impress Study involves nurses who are assessing lifestyle risk and developing an action plan according to a standardized procedure, which may be advantageous given the degree of heterogeneity found in other TBC models.51 There are also studies underway or recently published that compare different components of TBC in order to determine which combination of TBC elements is preferred. Some of these have shown the benefits of using clinical decision-support systems (through a guideline-based treatment protocol) or training programs with ongoing support.52,53 Continued research comparing different TBC models is needed to determine which combination of health professionals and interventions is most impactful in practice.
Cost-Effectiveness
According to the CDC, TBC in hypertension management has proven to be cost-effective.54 Systematic reviews and meta-analyses assessing the cost-effectiveness of TBC in hypertension management have been conducted.26,27,29,55-58 While the general consensus supports this approach as being cost-effective, these determinations are based on studies that are widely heterogeneous. In each of these studies, different types of costs are taken into account when determining cost-effectiveness. The range of costs can be quite wide, depending on how they are calculated, making it difficult to determine the true cost-effectiveness of different TBC models.
Intervention cost is represented by the amount of money spent to implement and maintain the intervention beyond the cost of usual care or the cost without the intervention. For TBC, intervention cost consists of personnel resources such as provider time, patient time, and non-personnel resources, including rent and utilities. Studies show that intervention costs for TBC can range from $35 to $1350 per person per year (mean, $618; median, $428).27,56 One analysis, based on 20 studies comparing TBC to usual care, calculated an intervention cost of $284 per person per year,55 while another study showed an intervention cost of $525 per enrollee per year.56 Intervention cost can vary by the type of provider that is used, the amount of time spent per patient, and the setting where services are provided. Overall, the intervention cost of implementing TBC for hypertension management is consistently higher than the cost of usual care.
Health care cost is another factor to consider. It is the difference in the cost of health care products and services that are utilized in the process of TBC, as compared to care that is provided in the absence of TBC. Health care costs include the costs associated with hospitalizations, outpatient visits, emergency room visits, and medications. One study estimated a median health care cost of hypertension TBC of $65 per person per year.55 Overall, studies evaluating the impact of TBC for hypertension management on health care costs were mixed, with some showing that TBC resulted in an increase in health care cost, and others showing a savings compared to usual care.58 The variability in health care costs was due to the different number of health care components and comorbidities of the patients included in the studies. Also, study duration affected the estimated health care costs of TBC. Most studies did not assess long-term health care cost savings that could be achieved from prolonged blood pressure control.58 When considering both intervention and health care cost, Jacob et al estimated that TBC increased overall net cost by a median value of $329 per person per year.55 While some studies did attribute an overall reduction in health care costs to TBC for hypertension management, on average, team-based models increased health care costs compared to usual care.27,29,55,58,59
However, health care costs do not take into account the long-term reductions in morbidity and mortality or increased quality-adjusted life years (QALY) that result from improved blood pressure control attributed to TBC. In most cost-effectiveness studies, an intervention is considered to be cost-effective if the cost per QALY gained is less than the accepted threshold of $50,000.55 One study estimated that the cost per QALY of TBC in hypertension management is $4763,55,60 while another study estimated a median cost per QALY of $9716 to $13,992.55 A systematic review of 34 international studies estimated the median cost per QALY to be $13,986, ranging from $6683 to $58,610.57 The wide range in cost can be attributed to the variability in interventions, health outcomes used to measure effectiveness, and the settings and countries where the studies were conducted. In another study, a TBC intervention involving pharmacists resulted in a cost per QALY of $26,800.61 The intervention was found to be cost-effective for higher-risk patients, defined as those having diabetes, a smoking history, dyslipidemia, or obesity. For patients who did not have these risk factors, the cost per QALY increased to $43,330.61 Thus, the patient population should be considered before implementing a TBC model. Furthermore, the increased use of technology, allowing for more efficient provision of services and communication between providers, could reduce intervention costs and lead to increased cost efficacy in these models.
The variation in the models used for TBC makes it difficult to draw conclusions on the cost-effectiveness of these interventions. Although it is apparent that TBC in general is cost-effective, more studies are needed comparing different team-based models to determine which specific ones are most cost-effective.
Challenges to Implementation of Team-Based Care
Recognizing and addressing the challenges inherent to a TBC approach is important to the sustainability of such a model within various settings and institutions. Numerous studies conducted on team-based models have identified common challenges that appear to be consistent across multiple settings. These challenges can be categorized as financial, provider-specific, and technology.
Financial Barriers
Although studies have demonstrated the cost-effectiveness of controlling hypertension and preventing serious complications, health systems are still confronted with the challenge of covering the cost for TBC implementation and maintenance.29 The 2 main financial barriers for TBC services are stakeholder engagement and reimbursement for services. According to Kennelty et al, stakeholder engagement is key to the sustainability of the service.27 However, decisions by stakeholders on cost are influenced by many factors, which include available funds, perceived value, and estimates for return on investment. Additionally, interventions must align with the organization’s mission and vision and be feasible to implement, and organizations must have the capacity for administrative support.29 These various financial decisions may greatly influence the sustainability of a TBC model.
The reimbursement challenges for individual providers are an additional barrier to the sustainability of the service. In the United States, most providers are reimbursed via fee-for-service payment plans, but these plans do not reimburse all clinical providers because they are not all recognized as licensed providers.62,63 For example, pharmacists are not recognized by the Centers for Medicare & Medicaid Services as licensed health care providers, which limits their ability to be reimbursed for clinical services provided outside of a traditional dispensing role. Furthermore, state laws determine the services nonphysician providers can offer and how they are recognized for reimbursement by tertiary payers. For instance, pharmacist roles, such as ordering labs and modifying or prescribing medication regimens, vary greatly between states.7,63,64
Financial barriers are a major challenge facing the sustainability of a TBC hypertension service, so including all stakeholders in the decision-making process may improve the organization’s ability to sustain the service.
Provider-Specific Barriers
Notable barriers that are attributed to providers include lack of knowledge, lack of time, lack of initiative to change blood pressure medications, and inability to reach intensive blood pressure goals set in guidelines.29 Studies such as the SPRINT trial have significantly impacted clinical guideline cut-offs for blood pressure, but reaching the intensive blood pressure goals from clinical trials is difficult to emulate in clinical practice.65 In a typical clinical setting, providers may lack the confidence to make adjustments in therapy based on a single blood pressure measurement, and clinical inertia, defined as failure of health care providers to modify therapy when indicated,66 may contribute to the inability to achieve blood pressure goals. Many factors contribute to clinical inertia, including lack of knowledge, time, or clinical protocols on how to modify therapy, causing providers to delay clinical decisions. Implementing site-specific protocols and utilizing hypertension specialist health care professionals in TBC can address the barriers contributing to clinical inertia.
Technology Barriers
A common barrier in a variety of services, but especially prevalent in a TBC service, is access to an electronic health record (EHR) for all providers treating the patient. Some providers who are not directly tied to the same clinical site as the patient’s primary care provider may not have adequate access to the full EHR. For example, pharmacists who are managing hypertension in a TBC model in a community pharmacy may have access only to health information from prescription records. Patient interviews may not provide the pharmacist with adequate information about laboratory results, vitals, and other medical information and history for the patient, making it difficult for the pharmacist to make a proper recommendation for treatment.27 Depending on the setting, communication between providers may be a barrier in achieving optimal outcomes, especially when providers do not have access to a shared medical record.
In addition, patients often lack access to technology used to manage hypertension. Many new technologies exist that aid patients in managing their blood pressure, such as smart phone applications to track blood pressure readings and alarms to remind patients to take their medications. Studies have shown that telemonitoring of blood pressure measurements and management of hypertension, especially in combination with TBC, is effective and reduces costs compared to usual care.67 However, the lack of equal access to the various technologies available may inhibit the success of a TBC hypertension program. Patients may lack access, knowledge, or financial means to utilize the various methods available for managing their hypertension electronically.29
Conclusion
Incorporating nonphysician providers into the health care team for the treatment of hypertension has proven to be more effective than usual care and has been recognized by recent guidelines as a best practice approach to achieving blood pressure goals. Multiple studies have demonstrated that TBC utilizing nurses and pharmacists can improve blood pressure management. While adding members to the team increases health care costs, the long-term benefits of achieving optimal blood pressure goals contribute to the overall cost-effectiveness of TBC strategies over usual care. However, comparisons between different TBC models are warranted to determine which combination of health care professionals and/or interventions is most effective. Cost-analysis estimates are difficult to compare due to widely varied methodology and variance in the models that have been employed. Studies must consider pathways to overcoming reimbursement issues, provider-specific challenges, and technology barriers. Follow-up and monitoring after initiation of drug therapy for hypertension control should include systematic strategies to help improve blood pressure, including use of home blood pressure monitoring, TBC, and telehealth strategies. Future implementation science approaches to hypertension TBC models within specific clinic settings will be useful to identify and overcome challenges and will help to determine the populations who will benefit most, allowing for greater success in sustaining TBC models.
Corresponding author: Shawn R. Smith, PharmD, 309 E. 2nd Street, Pomona, CA 91766; shawnsmith@westernu.edu.
Financial disclosures: None.
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62. Lall D, Engel N, Devadasan N, et al. Models of care for chronic conditions in low/middle-income countries: a ‘best fit’ framework synthesis. BMJ Glob Health. 2018;3:e001077.
63. Bodenheimer T, Chen E, Bennett HD. Confronting the growing burden of chronic disease: can the U.S. health care workforce do the job? Health Aff (Millwood). 2009;28:64-74.
64. Smith M, Bates DW, Bodenheimer T, Cleary PD. Why pharmacists belong in the medical home. Health Aff (Millwood). 2010;29:906-913.
65. Wright JT, Williamson JD, Whelton PK, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373:2103-2116.
66. Phillips LS, Branch WT, Cook CB, et al. Clinical inertia. Ann Intern Med. 2001;135:825-834.
67. McManus RJ, Mant J, Franssen M, et al. Efficacy of self-monitored blood pressure, with or without telemonitoring, for titration of antihypertensive medication (TASMINH4): an unmasked randomised controlled trial. Lancet. 2018;391:949-959.
68. Tucker KL, Sheppard JP, Stevens R, et al. Self-monitoring of blood pressure in hypertension: a systematic review and individual patient data meta-analysis. PLoS Med. 2017;14:e1002389.
69. Casey DE, Thomas RJ, Bhalla V, et al. 2019 AHA/ACC clinical performance and quality measures for adults with high blood pressure: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures. J Am Coll Cardiol. 2019;74:2661-2706.
From Western University of Health Sciences College of Pharmacy, Department of Pharmacy Practice and Administration, Pomona, CA.
Abstract
- Objective: To review the current literature regarding the clinical effectiveness and cost-effectiveness of implementing hypertension team-based care (TBC) interventions in the outpatient setting, and discuss challenges to implementation.
- Methods: A literature review was conducted of meta-analyses, systematic reviews, and randomized controlled trials comparing TBC models to usual care for hypertension management.
- Results: Compared to usual care, TBC models have demonstrated greater blood pressure reductions and improved blood pressure control rates. Evidence was strongest for models involving nurses and pharmacists whose roles included medication management, patient education and counseling, coordination of care and follow-up, population health management, and performance measurement with quality improvement. Although TBC results in an increase in health care costs, the overall long-term benefits support the cost-effectiveness of these models over usual care. The most common barriers to TBC implementation include underutilization of technology, stakeholder engagement, and reimbursement issues.
- Conclusion: Hypertension TBC models have been shown to be clinically effective and cost-effective, but continued research comparing different models is warranted to determine which combination of health professionals and interventions is most impactful and cost-effective in practice. An implementation science approach, in which TBC models unique to each organization’s situation are created, will be useful to identify and overcome challenges and provide a solid foundation for sustainment.
Keywords: blood pressure; pharmacist; nurse; nurse practitioner; cost-effectiveness; team-based care.
Approximately 1 in 3 US adults—or about 100 million people—have high blood pressure, and only about half (48%) have their blood pressure under control.1 Effective blood pressure management has been shown to decrease the incidence of stroke, heart attack, and heart failure.2-4 The American College of Cardiology/American Heart Association (ACC/AHA) 2017 blood pressure guidelines recommended lower thresholds for diagnosing hypertension and initiating antihypertensive medication, and intensified the blood pressure goal to less than 130/80 mm Hg.5 Changing practice standards to more intensive blood pressure goals requires significant adjustments by clinicians and health care systems. In fact, new guideline uptake is often delayed, ignored, or sparsely applied.6 Due to this dramatic change in hypertension practice standards, the ACC/AHA guidelines support interdisciplinary team-based care (TBC) for hypertension management.5,7 Additionally, the Centers for Disease Control and Prevention (CDC) and the Community Preventive Services Task Force (CPSTF) promote TBC to improve blood pressure control in their initiatives to prevent heart disease and stroke.8,9
The National Academy of Medicine defines TBC as “the provision of health services to individuals, families, and/or their communities by at least 2 healthcare providers who work collaboratively with patients and their caregivers—to the extent preferred by each patient—to accomplish shared goals within and across settings to achieve coordinated, high-quality care.”10 Specific goals for TBC in hypertension treatment are listed in Table 1, and a checklist of key elements of TBC to consider before implementation are presented in Table 2.
TBC has been shown to have many advantages, including increased access to care due to expanded hours of operation and shorter wait times.11 Team-based models also provide effective and efficient delivery of patient education, behavioral health care, and care coordination.12-14 Patients are more likely to receive high-quality care when multiple providers, each with varied expertise, are on the health care team.11,15 Furthermore, clinicians report improved professional job satisfaction related to their ability to practice in environments where they are encouraged to work at the top of their licenses.16 Consequently, TBC has been accepted as a vital part of the patient-centered medical home (PCMH) model.17-19 Standards set by the National Committee for Quality Assurance (NCQA) include TBC as a requirement health systems must meet in order to achieve the highest level of PCMH recognition. While a team-based approach offers substantial benefits and is recognized as a marker of quality, implementation has presented various challenges, and the sustainability of these models in care settings has been questioned.20
In this article, we review the current literature regarding the clinical effectiveness and cost-effectiveness of implementing hypertension TBC interventions in the outpatient setting. We also discuss the challenges and opportunities of implementing this strategy in health systems and community settings in the United States.
Evidence of Impact and Effectiveness
Various models of hypertension TBC have been shown to increase the proportion of individuals with controlled blood pressure and to lead to a reduction in both systolic (SBP) and diastolic blood pressure (DBP), resulting in a strong recommendation for TBC approaches by the 2017 ACC/AHA blood pressure guidelines.5,21-25 There is great diversity in the types of hypertension treatment models studied, with few utilizing physician specialists and most utilizing nonphysician providers, such as community health workers, physician assistants, nurses, nurse practitioners, dietitians, social workers, and pharmacists.22,26-29 These professionals share duties of hypertension management with primary care physicians to reduce the burden of responsibility for care on any single provider type. TBC is patient-centered, and typically includes interprofessional collaboration, treatment algorithms, adherence counseling, frequent follow-up, home blood pressure monitoring, and patient self-management education.
Numerous studies have supported implementation of TBC in recent years. A systematic review and meta-analysis of 100 trials of hypertension TBC involving 55,920 patients concluded that the most effective blood pressure–lowering strategies use multilevel, multicomponent approaches to address barriers to hypertension control. Nonphysician providers are often involved in measuring blood pressure, ordering and assessing laboratory tests, and titrating medications.30 Compared with usual care, TBC with physician medication titration resulted in reductions in mean SBP and DBP (6.2 mm Hg and 2.7 mm Hg, respectively), while TBC with nonphysician medication titration also resulted in reductions in mean SBP and DBP (7.1 mm Hg and 3.1 mm Hg, respectively). Nurses and pharmacists are specifically mentioned by the 2017 ACC/AHA blood pressure guidelines as essential members of the hypertension treatment team.5 Randomized controlled trials (RCTs) and meta-analyses of TBC involving nurse or pharmacist interventions demonstrated greater reductions in SBP and/or greater attainment of blood pressure goals compared to usual care.21,26,31,32 The literature supports the roles of nurses and pharmacists in hypertension management in all aspects of care, including medication management, patient education and counseling, coordination of care and follow-up, population health management, and performance measurement with quality improvement.33
Nurses
Nurses are commonly part of TBC hypertension management programs. One meta-analysis and systematic review of international RCTs compared nurse, nurse prescriber (United Kingdom), and nurse practitioner interventions for hypertension with usual care. Interventions that included a stepped treatment algorithm and nurse prescribing showed greater reductions in SBP (8.2 mm Hg and 8.9 mm Hg, respectively) compared to usual care.31 Similarly, models that utilized telephone monitoring demonstrated greater achievement of blood pressure targets, while those that involved home monitoring showed significant reductions in blood pressure. Another international meta-analysis and systematic review of 11 nurse-led interventions in hypertensive patients with diabetes demonstrated a 5.8 mm Hg mean decrease in SBP compared to physician-led care. However, nurse-led care was not superior in achievement of study targets.34
A recent meta-analysis and systematic review, performed by Shaw and colleagues, sought to determine whether nurse-led protocols are effective for outpatient management of adults with diabetes, hypertension, and hyperlipidemia. All of the included studies involved a registered nurse who titrated medications by following a protocol, and most were RCTs comparing the nurse protocols to usual care. Overall, mean SBP and DBP decreased by 3.86 mm Hg and 1.56 mm Hg, respectively, while blood glucose and lipid levels were also reduced compared to usual care.24
Limited RCT data have been published since the Shaw et al meta-analysis. A single-blind RCT was performed in an urban community health care center in China among patients with uncontrolled blood pressure (SBP ≥ 140 mm Hg and/or DBP ≥ 90 mm Hg).35 The study group received care via a nurse-led model, which included a delivery design system, decision support, clinical information system, and self-management support, and the control group received usual care. At 12 weeks, patients in the study group had significantly lower blood pressure than control patients, with mean SBP/DBP reduction of 14.37/7.43 mm Hg and 5.10/2.69 mm Hg, respectively (P < 0.01). Improved medication adherence and increased patient satisfaction were other benefits of the nurse-led model.
Nurse case managers (NCM) also play a critical role in hypertension management, coordinating health care services to meet patient health needs. Ogedegbe sought to evaluate the comparative effectiveness of home blood pressure telemonitoring (HBPTM)+NCM versus HBPTM alone on SBP reduction in black and Hispanic stroke survivors.36,37 NCMs evaluated patient profiles, counseled patients on target lifestyle behaviors, and reviewed home blood pressure data. At 6 months, SBP declined by 13.63 mm Hg from baseline in the HBPTM+NCM group and 6.31 mm Hg in the HBPTM alone group (P < 0.0001). At 12 months, SBP in the HBPTM+NCM group declined by 14.76 mm Hg, while blood pressure in the HBPTM alone group declined by 5.53 mm Hg (P < 0.0001).
Pharmacists
Clinical pharmacists are also widely utilized in TBC models for hypertension management. Typical models involve pharmacists entering into collaborative practice agreements with physicians, leading to optimization of medications, avoidance of adverse drug events, and transitional care activities focusing on medication reconciliation and patient education in outpatient settings.30,38 The largest and most recent meta-analysis of pharmacist interventions, conducted in 2014 by Santschi et al,23 combined 2 previous systematic reviews to include a total of 39 RCTs with 14,224 patients.32,39 Pharmacist interventions included patient education, recommendations to physicians, and medication management. Compared with usual care, pharmacist interventions showed greater reductions in SBP (7.6 mm Hg) and DBP (3.9 mm Hg).23
Numerous studies substantiating the impact of pharmacist interventions on clinical outcomes have heavily influenced clinical practice and guideline development. Carter et al conducted a prospective, multi-state, cluster-randomized trial in 32 primary care clinics to evaluate whether clinics randomized to receive the pharmacist-physician collaborative care model (PPCCM) achieved better blood pressure outcomes versus clinics randomized to usual care.25 Investigators enrolled 625 patients with uncontrolled hypertension, 50% of whom had a prior diagnosis of diabetes mellitus or chronic kidney disease. The primary outcome of blood pressure control at 9 months in the intervention clinics compared to the control clinics was 43% and 34%, respectively (P = 0.059). The difference in mean SBP/DBP between the intervention and control clinics for all patients at 9 months was −6.1/−2.9 mm Hg. In a post-hoc analysis of patients with chronic kidney disease and diabetes, the pharmacist-intervention group had a significantly greater mean SBP reduction and higher blood pressure control rates compared to usual care at 9 months.40
A pre-specified secondary analysis from the Carter et al study determined that, in patients from racial minority groups, the mean SBP was 7.3 mm Hg lower in those who received the intervention compared to those in the control group (P = 0.0042).41 In patients with less than 12 years of education, those in the intervention group had a mean SBP 8.1 mm Hg lower than the SBP of those in the control group (P = 0.0001). Similar reductions in blood pressure occurred in patients with low income, Medicaid beneficiaries, or those without insurance. This study demonstrated that pharmacist interventions reduced racial and socioeconomic disparities in blood pressure treatment.
Other studies of pharmacist interventions in underserved populations have yielded positive results. In a retrospective review of uninsured patients, blood pressure control rates in a pharmacist-driven primary care clinic ranked in the 90th percentile of NCQA benchmarks, and was superior to the 2013 reported mean for commercial insurers.42 Similarly, another retrospective cohort study of a PPCCM on time to goal blood pressure in uninsured patients with hypertension showed the median time to blood pressure goal was 36 days in the PPCCM cohort versus 259 days in usual care cohorts (P < 0.001).43 A post-hoc analysis revealed the mean time-in-therapeutic blood pressure range was 46.2% ± 24.3% in the PPCCM group and 24.8% ± 27.4% in the usual care group (P < 0.0001). The blood pressure control rates at 12 months were 89% in the PPCCM group compared with 50% in the usual care group (P < 0.0001).44
Tsuyuki et al conducted the RxACTION study, a multicenter RCT evaluating the effectiveness of enhanced pharmacist care versus usual care in 23 Canadian community pharmacies and outpatient clinics following a 6-month intervention.45 Enhanced pharmacy services included pharmacist assessment of and counseling about cardiovascular disease risk and blood pressure control, review of current antihypertensive medications, and prescribing/titrating drug therapy, as needed, through independent prescriptive authority. Compared to the usual care group (n = 67), the intervention group had a reduction in SBP of 6.6 mm Hg (P = 0.006) and in DBP of 3.2 mm Hg (P = 0.01). This study expanded the pharmacists’ scope of practice, showing evidence for enhancing pharmacist roles on the hypertension care team. Tsuyuki et al also conducted the RxEACH randomized trial, which evaluated community pharmacist cardiovascular risk reduction interventions and showed an improvement in SBP and DBP, with reported results comparable to RxACTION.46
Victor et al conducted the landmark Black Barbershop Study, a cluster RCT involving 319 non-Hispanic black male patients with hypertension from 52 black-owned barbershops.47,48 Barbershops were assigned to 1 of 2 groups. The control group consisted of barbers who encouraged lifestyle modifications and made referrals to primary care providers. The intervention group had pharmacists who met regularly with participants at the barbershops and measured blood pressure, encouraged lifestyle changes, and prescribed drug therapy under collaborative practice agreements with physicians. Both groups demonstrated improvements in blood pressure outcomes, but the intervention group showed greater improvement in SBP and achievement of blood pressure goals compared to the control group. The results in the intervention group proved sustainable over the course of a year, even after the frequency of pharmacists’ visits was reduced. At 6 months, the mean SBP fell by 27.0 mm Hg (to 125.8 mm Hg) in the intervention group, as compared to a 9.3 mm Hg (to 145.4 mm Hg) reduction in the control group (P < 0.001), and blood pressure less than 130/80 mm Hg was achieved among 63.6% of the participants in the intervention group versus 11.7% in the control group (P < 0.001).
This community-level trial brought pharmacists to the barbershop and made them an essential part of the health care team through the endorsement of the barber, who the participants trusted and with whom they had a relationship. Long-standing issues related to distrust of the medical profession by this population were addressed, and trusted community barbershops were utilized as safe spaces for health care delivery. Health care professionals should consider utilizing community locations that other minority populations perceive as social centers and safe places, to reduce health disparities and barriers to care. However, models that bring care to patients need further economic and feasibility evaluations.
Other Health Care Professionals and Future Studies
In addition to models led by nurses and pharmacists, studies have also assessed models of TBC incorporating other health care professionals, including registered dietitians, medical assistants, community health workers, and health coaches (NCT02674464).49,50 Ongoing studies are also looking at the impact of TBC on underserved communities (NCT02674464, NCT03504124). Involving a variety of health care professionals with different communities and populations in TBC studies is warranted to determine the optimal settings in which to utilize different skill sets.
The Impress Study involves nurses who are assessing lifestyle risk and developing an action plan according to a standardized procedure, which may be advantageous given the degree of heterogeneity found in other TBC models.51 There are also studies underway or recently published that compare different components of TBC in order to determine which combination of TBC elements is preferred. Some of these have shown the benefits of using clinical decision-support systems (through a guideline-based treatment protocol) or training programs with ongoing support.52,53 Continued research comparing different TBC models is needed to determine which combination of health professionals and interventions is most impactful in practice.
Cost-Effectiveness
According to the CDC, TBC in hypertension management has proven to be cost-effective.54 Systematic reviews and meta-analyses assessing the cost-effectiveness of TBC in hypertension management have been conducted.26,27,29,55-58 While the general consensus supports this approach as being cost-effective, these determinations are based on studies that are widely heterogeneous. In each of these studies, different types of costs are taken into account when determining cost-effectiveness. The range of costs can be quite wide, depending on how they are calculated, making it difficult to determine the true cost-effectiveness of different TBC models.
Intervention cost is represented by the amount of money spent to implement and maintain the intervention beyond the cost of usual care or the cost without the intervention. For TBC, intervention cost consists of personnel resources such as provider time, patient time, and non-personnel resources, including rent and utilities. Studies show that intervention costs for TBC can range from $35 to $1350 per person per year (mean, $618; median, $428).27,56 One analysis, based on 20 studies comparing TBC to usual care, calculated an intervention cost of $284 per person per year,55 while another study showed an intervention cost of $525 per enrollee per year.56 Intervention cost can vary by the type of provider that is used, the amount of time spent per patient, and the setting where services are provided. Overall, the intervention cost of implementing TBC for hypertension management is consistently higher than the cost of usual care.
Health care cost is another factor to consider. It is the difference in the cost of health care products and services that are utilized in the process of TBC, as compared to care that is provided in the absence of TBC. Health care costs include the costs associated with hospitalizations, outpatient visits, emergency room visits, and medications. One study estimated a median health care cost of hypertension TBC of $65 per person per year.55 Overall, studies evaluating the impact of TBC for hypertension management on health care costs were mixed, with some showing that TBC resulted in an increase in health care cost, and others showing a savings compared to usual care.58 The variability in health care costs was due to the different number of health care components and comorbidities of the patients included in the studies. Also, study duration affected the estimated health care costs of TBC. Most studies did not assess long-term health care cost savings that could be achieved from prolonged blood pressure control.58 When considering both intervention and health care cost, Jacob et al estimated that TBC increased overall net cost by a median value of $329 per person per year.55 While some studies did attribute an overall reduction in health care costs to TBC for hypertension management, on average, team-based models increased health care costs compared to usual care.27,29,55,58,59
However, health care costs do not take into account the long-term reductions in morbidity and mortality or increased quality-adjusted life years (QALY) that result from improved blood pressure control attributed to TBC. In most cost-effectiveness studies, an intervention is considered to be cost-effective if the cost per QALY gained is less than the accepted threshold of $50,000.55 One study estimated that the cost per QALY of TBC in hypertension management is $4763,55,60 while another study estimated a median cost per QALY of $9716 to $13,992.55 A systematic review of 34 international studies estimated the median cost per QALY to be $13,986, ranging from $6683 to $58,610.57 The wide range in cost can be attributed to the variability in interventions, health outcomes used to measure effectiveness, and the settings and countries where the studies were conducted. In another study, a TBC intervention involving pharmacists resulted in a cost per QALY of $26,800.61 The intervention was found to be cost-effective for higher-risk patients, defined as those having diabetes, a smoking history, dyslipidemia, or obesity. For patients who did not have these risk factors, the cost per QALY increased to $43,330.61 Thus, the patient population should be considered before implementing a TBC model. Furthermore, the increased use of technology, allowing for more efficient provision of services and communication between providers, could reduce intervention costs and lead to increased cost efficacy in these models.
The variation in the models used for TBC makes it difficult to draw conclusions on the cost-effectiveness of these interventions. Although it is apparent that TBC in general is cost-effective, more studies are needed comparing different team-based models to determine which specific ones are most cost-effective.
Challenges to Implementation of Team-Based Care
Recognizing and addressing the challenges inherent to a TBC approach is important to the sustainability of such a model within various settings and institutions. Numerous studies conducted on team-based models have identified common challenges that appear to be consistent across multiple settings. These challenges can be categorized as financial, provider-specific, and technology.
Financial Barriers
Although studies have demonstrated the cost-effectiveness of controlling hypertension and preventing serious complications, health systems are still confronted with the challenge of covering the cost for TBC implementation and maintenance.29 The 2 main financial barriers for TBC services are stakeholder engagement and reimbursement for services. According to Kennelty et al, stakeholder engagement is key to the sustainability of the service.27 However, decisions by stakeholders on cost are influenced by many factors, which include available funds, perceived value, and estimates for return on investment. Additionally, interventions must align with the organization’s mission and vision and be feasible to implement, and organizations must have the capacity for administrative support.29 These various financial decisions may greatly influence the sustainability of a TBC model.
The reimbursement challenges for individual providers are an additional barrier to the sustainability of the service. In the United States, most providers are reimbursed via fee-for-service payment plans, but these plans do not reimburse all clinical providers because they are not all recognized as licensed providers.62,63 For example, pharmacists are not recognized by the Centers for Medicare & Medicaid Services as licensed health care providers, which limits their ability to be reimbursed for clinical services provided outside of a traditional dispensing role. Furthermore, state laws determine the services nonphysician providers can offer and how they are recognized for reimbursement by tertiary payers. For instance, pharmacist roles, such as ordering labs and modifying or prescribing medication regimens, vary greatly between states.7,63,64
Financial barriers are a major challenge facing the sustainability of a TBC hypertension service, so including all stakeholders in the decision-making process may improve the organization’s ability to sustain the service.
Provider-Specific Barriers
Notable barriers that are attributed to providers include lack of knowledge, lack of time, lack of initiative to change blood pressure medications, and inability to reach intensive blood pressure goals set in guidelines.29 Studies such as the SPRINT trial have significantly impacted clinical guideline cut-offs for blood pressure, but reaching the intensive blood pressure goals from clinical trials is difficult to emulate in clinical practice.65 In a typical clinical setting, providers may lack the confidence to make adjustments in therapy based on a single blood pressure measurement, and clinical inertia, defined as failure of health care providers to modify therapy when indicated,66 may contribute to the inability to achieve blood pressure goals. Many factors contribute to clinical inertia, including lack of knowledge, time, or clinical protocols on how to modify therapy, causing providers to delay clinical decisions. Implementing site-specific protocols and utilizing hypertension specialist health care professionals in TBC can address the barriers contributing to clinical inertia.
Technology Barriers
A common barrier in a variety of services, but especially prevalent in a TBC service, is access to an electronic health record (EHR) for all providers treating the patient. Some providers who are not directly tied to the same clinical site as the patient’s primary care provider may not have adequate access to the full EHR. For example, pharmacists who are managing hypertension in a TBC model in a community pharmacy may have access only to health information from prescription records. Patient interviews may not provide the pharmacist with adequate information about laboratory results, vitals, and other medical information and history for the patient, making it difficult for the pharmacist to make a proper recommendation for treatment.27 Depending on the setting, communication between providers may be a barrier in achieving optimal outcomes, especially when providers do not have access to a shared medical record.
In addition, patients often lack access to technology used to manage hypertension. Many new technologies exist that aid patients in managing their blood pressure, such as smart phone applications to track blood pressure readings and alarms to remind patients to take their medications. Studies have shown that telemonitoring of blood pressure measurements and management of hypertension, especially in combination with TBC, is effective and reduces costs compared to usual care.67 However, the lack of equal access to the various technologies available may inhibit the success of a TBC hypertension program. Patients may lack access, knowledge, or financial means to utilize the various methods available for managing their hypertension electronically.29
Conclusion
Incorporating nonphysician providers into the health care team for the treatment of hypertension has proven to be more effective than usual care and has been recognized by recent guidelines as a best practice approach to achieving blood pressure goals. Multiple studies have demonstrated that TBC utilizing nurses and pharmacists can improve blood pressure management. While adding members to the team increases health care costs, the long-term benefits of achieving optimal blood pressure goals contribute to the overall cost-effectiveness of TBC strategies over usual care. However, comparisons between different TBC models are warranted to determine which combination of health care professionals and/or interventions is most effective. Cost-analysis estimates are difficult to compare due to widely varied methodology and variance in the models that have been employed. Studies must consider pathways to overcoming reimbursement issues, provider-specific challenges, and technology barriers. Follow-up and monitoring after initiation of drug therapy for hypertension control should include systematic strategies to help improve blood pressure, including use of home blood pressure monitoring, TBC, and telehealth strategies. Future implementation science approaches to hypertension TBC models within specific clinic settings will be useful to identify and overcome challenges and will help to determine the populations who will benefit most, allowing for greater success in sustaining TBC models.
Corresponding author: Shawn R. Smith, PharmD, 309 E. 2nd Street, Pomona, CA 91766; shawnsmith@westernu.edu.
Financial disclosures: None.
From Western University of Health Sciences College of Pharmacy, Department of Pharmacy Practice and Administration, Pomona, CA.
Abstract
- Objective: To review the current literature regarding the clinical effectiveness and cost-effectiveness of implementing hypertension team-based care (TBC) interventions in the outpatient setting, and discuss challenges to implementation.
- Methods: A literature review was conducted of meta-analyses, systematic reviews, and randomized controlled trials comparing TBC models to usual care for hypertension management.
- Results: Compared to usual care, TBC models have demonstrated greater blood pressure reductions and improved blood pressure control rates. Evidence was strongest for models involving nurses and pharmacists whose roles included medication management, patient education and counseling, coordination of care and follow-up, population health management, and performance measurement with quality improvement. Although TBC results in an increase in health care costs, the overall long-term benefits support the cost-effectiveness of these models over usual care. The most common barriers to TBC implementation include underutilization of technology, stakeholder engagement, and reimbursement issues.
- Conclusion: Hypertension TBC models have been shown to be clinically effective and cost-effective, but continued research comparing different models is warranted to determine which combination of health professionals and interventions is most impactful and cost-effective in practice. An implementation science approach, in which TBC models unique to each organization’s situation are created, will be useful to identify and overcome challenges and provide a solid foundation for sustainment.
Keywords: blood pressure; pharmacist; nurse; nurse practitioner; cost-effectiveness; team-based care.
Approximately 1 in 3 US adults—or about 100 million people—have high blood pressure, and only about half (48%) have their blood pressure under control.1 Effective blood pressure management has been shown to decrease the incidence of stroke, heart attack, and heart failure.2-4 The American College of Cardiology/American Heart Association (ACC/AHA) 2017 blood pressure guidelines recommended lower thresholds for diagnosing hypertension and initiating antihypertensive medication, and intensified the blood pressure goal to less than 130/80 mm Hg.5 Changing practice standards to more intensive blood pressure goals requires significant adjustments by clinicians and health care systems. In fact, new guideline uptake is often delayed, ignored, or sparsely applied.6 Due to this dramatic change in hypertension practice standards, the ACC/AHA guidelines support interdisciplinary team-based care (TBC) for hypertension management.5,7 Additionally, the Centers for Disease Control and Prevention (CDC) and the Community Preventive Services Task Force (CPSTF) promote TBC to improve blood pressure control in their initiatives to prevent heart disease and stroke.8,9
The National Academy of Medicine defines TBC as “the provision of health services to individuals, families, and/or their communities by at least 2 healthcare providers who work collaboratively with patients and their caregivers—to the extent preferred by each patient—to accomplish shared goals within and across settings to achieve coordinated, high-quality care.”10 Specific goals for TBC in hypertension treatment are listed in Table 1, and a checklist of key elements of TBC to consider before implementation are presented in Table 2.
TBC has been shown to have many advantages, including increased access to care due to expanded hours of operation and shorter wait times.11 Team-based models also provide effective and efficient delivery of patient education, behavioral health care, and care coordination.12-14 Patients are more likely to receive high-quality care when multiple providers, each with varied expertise, are on the health care team.11,15 Furthermore, clinicians report improved professional job satisfaction related to their ability to practice in environments where they are encouraged to work at the top of their licenses.16 Consequently, TBC has been accepted as a vital part of the patient-centered medical home (PCMH) model.17-19 Standards set by the National Committee for Quality Assurance (NCQA) include TBC as a requirement health systems must meet in order to achieve the highest level of PCMH recognition. While a team-based approach offers substantial benefits and is recognized as a marker of quality, implementation has presented various challenges, and the sustainability of these models in care settings has been questioned.20
In this article, we review the current literature regarding the clinical effectiveness and cost-effectiveness of implementing hypertension TBC interventions in the outpatient setting. We also discuss the challenges and opportunities of implementing this strategy in health systems and community settings in the United States.
Evidence of Impact and Effectiveness
Various models of hypertension TBC have been shown to increase the proportion of individuals with controlled blood pressure and to lead to a reduction in both systolic (SBP) and diastolic blood pressure (DBP), resulting in a strong recommendation for TBC approaches by the 2017 ACC/AHA blood pressure guidelines.5,21-25 There is great diversity in the types of hypertension treatment models studied, with few utilizing physician specialists and most utilizing nonphysician providers, such as community health workers, physician assistants, nurses, nurse practitioners, dietitians, social workers, and pharmacists.22,26-29 These professionals share duties of hypertension management with primary care physicians to reduce the burden of responsibility for care on any single provider type. TBC is patient-centered, and typically includes interprofessional collaboration, treatment algorithms, adherence counseling, frequent follow-up, home blood pressure monitoring, and patient self-management education.
Numerous studies have supported implementation of TBC in recent years. A systematic review and meta-analysis of 100 trials of hypertension TBC involving 55,920 patients concluded that the most effective blood pressure–lowering strategies use multilevel, multicomponent approaches to address barriers to hypertension control. Nonphysician providers are often involved in measuring blood pressure, ordering and assessing laboratory tests, and titrating medications.30 Compared with usual care, TBC with physician medication titration resulted in reductions in mean SBP and DBP (6.2 mm Hg and 2.7 mm Hg, respectively), while TBC with nonphysician medication titration also resulted in reductions in mean SBP and DBP (7.1 mm Hg and 3.1 mm Hg, respectively). Nurses and pharmacists are specifically mentioned by the 2017 ACC/AHA blood pressure guidelines as essential members of the hypertension treatment team.5 Randomized controlled trials (RCTs) and meta-analyses of TBC involving nurse or pharmacist interventions demonstrated greater reductions in SBP and/or greater attainment of blood pressure goals compared to usual care.21,26,31,32 The literature supports the roles of nurses and pharmacists in hypertension management in all aspects of care, including medication management, patient education and counseling, coordination of care and follow-up, population health management, and performance measurement with quality improvement.33
Nurses
Nurses are commonly part of TBC hypertension management programs. One meta-analysis and systematic review of international RCTs compared nurse, nurse prescriber (United Kingdom), and nurse practitioner interventions for hypertension with usual care. Interventions that included a stepped treatment algorithm and nurse prescribing showed greater reductions in SBP (8.2 mm Hg and 8.9 mm Hg, respectively) compared to usual care.31 Similarly, models that utilized telephone monitoring demonstrated greater achievement of blood pressure targets, while those that involved home monitoring showed significant reductions in blood pressure. Another international meta-analysis and systematic review of 11 nurse-led interventions in hypertensive patients with diabetes demonstrated a 5.8 mm Hg mean decrease in SBP compared to physician-led care. However, nurse-led care was not superior in achievement of study targets.34
A recent meta-analysis and systematic review, performed by Shaw and colleagues, sought to determine whether nurse-led protocols are effective for outpatient management of adults with diabetes, hypertension, and hyperlipidemia. All of the included studies involved a registered nurse who titrated medications by following a protocol, and most were RCTs comparing the nurse protocols to usual care. Overall, mean SBP and DBP decreased by 3.86 mm Hg and 1.56 mm Hg, respectively, while blood glucose and lipid levels were also reduced compared to usual care.24
Limited RCT data have been published since the Shaw et al meta-analysis. A single-blind RCT was performed in an urban community health care center in China among patients with uncontrolled blood pressure (SBP ≥ 140 mm Hg and/or DBP ≥ 90 mm Hg).35 The study group received care via a nurse-led model, which included a delivery design system, decision support, clinical information system, and self-management support, and the control group received usual care. At 12 weeks, patients in the study group had significantly lower blood pressure than control patients, with mean SBP/DBP reduction of 14.37/7.43 mm Hg and 5.10/2.69 mm Hg, respectively (P < 0.01). Improved medication adherence and increased patient satisfaction were other benefits of the nurse-led model.
Nurse case managers (NCM) also play a critical role in hypertension management, coordinating health care services to meet patient health needs. Ogedegbe sought to evaluate the comparative effectiveness of home blood pressure telemonitoring (HBPTM)+NCM versus HBPTM alone on SBP reduction in black and Hispanic stroke survivors.36,37 NCMs evaluated patient profiles, counseled patients on target lifestyle behaviors, and reviewed home blood pressure data. At 6 months, SBP declined by 13.63 mm Hg from baseline in the HBPTM+NCM group and 6.31 mm Hg in the HBPTM alone group (P < 0.0001). At 12 months, SBP in the HBPTM+NCM group declined by 14.76 mm Hg, while blood pressure in the HBPTM alone group declined by 5.53 mm Hg (P < 0.0001).
Pharmacists
Clinical pharmacists are also widely utilized in TBC models for hypertension management. Typical models involve pharmacists entering into collaborative practice agreements with physicians, leading to optimization of medications, avoidance of adverse drug events, and transitional care activities focusing on medication reconciliation and patient education in outpatient settings.30,38 The largest and most recent meta-analysis of pharmacist interventions, conducted in 2014 by Santschi et al,23 combined 2 previous systematic reviews to include a total of 39 RCTs with 14,224 patients.32,39 Pharmacist interventions included patient education, recommendations to physicians, and medication management. Compared with usual care, pharmacist interventions showed greater reductions in SBP (7.6 mm Hg) and DBP (3.9 mm Hg).23
Numerous studies substantiating the impact of pharmacist interventions on clinical outcomes have heavily influenced clinical practice and guideline development. Carter et al conducted a prospective, multi-state, cluster-randomized trial in 32 primary care clinics to evaluate whether clinics randomized to receive the pharmacist-physician collaborative care model (PPCCM) achieved better blood pressure outcomes versus clinics randomized to usual care.25 Investigators enrolled 625 patients with uncontrolled hypertension, 50% of whom had a prior diagnosis of diabetes mellitus or chronic kidney disease. The primary outcome of blood pressure control at 9 months in the intervention clinics compared to the control clinics was 43% and 34%, respectively (P = 0.059). The difference in mean SBP/DBP between the intervention and control clinics for all patients at 9 months was −6.1/−2.9 mm Hg. In a post-hoc analysis of patients with chronic kidney disease and diabetes, the pharmacist-intervention group had a significantly greater mean SBP reduction and higher blood pressure control rates compared to usual care at 9 months.40
A pre-specified secondary analysis from the Carter et al study determined that, in patients from racial minority groups, the mean SBP was 7.3 mm Hg lower in those who received the intervention compared to those in the control group (P = 0.0042).41 In patients with less than 12 years of education, those in the intervention group had a mean SBP 8.1 mm Hg lower than the SBP of those in the control group (P = 0.0001). Similar reductions in blood pressure occurred in patients with low income, Medicaid beneficiaries, or those without insurance. This study demonstrated that pharmacist interventions reduced racial and socioeconomic disparities in blood pressure treatment.
Other studies of pharmacist interventions in underserved populations have yielded positive results. In a retrospective review of uninsured patients, blood pressure control rates in a pharmacist-driven primary care clinic ranked in the 90th percentile of NCQA benchmarks, and was superior to the 2013 reported mean for commercial insurers.42 Similarly, another retrospective cohort study of a PPCCM on time to goal blood pressure in uninsured patients with hypertension showed the median time to blood pressure goal was 36 days in the PPCCM cohort versus 259 days in usual care cohorts (P < 0.001).43 A post-hoc analysis revealed the mean time-in-therapeutic blood pressure range was 46.2% ± 24.3% in the PPCCM group and 24.8% ± 27.4% in the usual care group (P < 0.0001). The blood pressure control rates at 12 months were 89% in the PPCCM group compared with 50% in the usual care group (P < 0.0001).44
Tsuyuki et al conducted the RxACTION study, a multicenter RCT evaluating the effectiveness of enhanced pharmacist care versus usual care in 23 Canadian community pharmacies and outpatient clinics following a 6-month intervention.45 Enhanced pharmacy services included pharmacist assessment of and counseling about cardiovascular disease risk and blood pressure control, review of current antihypertensive medications, and prescribing/titrating drug therapy, as needed, through independent prescriptive authority. Compared to the usual care group (n = 67), the intervention group had a reduction in SBP of 6.6 mm Hg (P = 0.006) and in DBP of 3.2 mm Hg (P = 0.01). This study expanded the pharmacists’ scope of practice, showing evidence for enhancing pharmacist roles on the hypertension care team. Tsuyuki et al also conducted the RxEACH randomized trial, which evaluated community pharmacist cardiovascular risk reduction interventions and showed an improvement in SBP and DBP, with reported results comparable to RxACTION.46
Victor et al conducted the landmark Black Barbershop Study, a cluster RCT involving 319 non-Hispanic black male patients with hypertension from 52 black-owned barbershops.47,48 Barbershops were assigned to 1 of 2 groups. The control group consisted of barbers who encouraged lifestyle modifications and made referrals to primary care providers. The intervention group had pharmacists who met regularly with participants at the barbershops and measured blood pressure, encouraged lifestyle changes, and prescribed drug therapy under collaborative practice agreements with physicians. Both groups demonstrated improvements in blood pressure outcomes, but the intervention group showed greater improvement in SBP and achievement of blood pressure goals compared to the control group. The results in the intervention group proved sustainable over the course of a year, even after the frequency of pharmacists’ visits was reduced. At 6 months, the mean SBP fell by 27.0 mm Hg (to 125.8 mm Hg) in the intervention group, as compared to a 9.3 mm Hg (to 145.4 mm Hg) reduction in the control group (P < 0.001), and blood pressure less than 130/80 mm Hg was achieved among 63.6% of the participants in the intervention group versus 11.7% in the control group (P < 0.001).
This community-level trial brought pharmacists to the barbershop and made them an essential part of the health care team through the endorsement of the barber, who the participants trusted and with whom they had a relationship. Long-standing issues related to distrust of the medical profession by this population were addressed, and trusted community barbershops were utilized as safe spaces for health care delivery. Health care professionals should consider utilizing community locations that other minority populations perceive as social centers and safe places, to reduce health disparities and barriers to care. However, models that bring care to patients need further economic and feasibility evaluations.
Other Health Care Professionals and Future Studies
In addition to models led by nurses and pharmacists, studies have also assessed models of TBC incorporating other health care professionals, including registered dietitians, medical assistants, community health workers, and health coaches (NCT02674464).49,50 Ongoing studies are also looking at the impact of TBC on underserved communities (NCT02674464, NCT03504124). Involving a variety of health care professionals with different communities and populations in TBC studies is warranted to determine the optimal settings in which to utilize different skill sets.
The Impress Study involves nurses who are assessing lifestyle risk and developing an action plan according to a standardized procedure, which may be advantageous given the degree of heterogeneity found in other TBC models.51 There are also studies underway or recently published that compare different components of TBC in order to determine which combination of TBC elements is preferred. Some of these have shown the benefits of using clinical decision-support systems (through a guideline-based treatment protocol) or training programs with ongoing support.52,53 Continued research comparing different TBC models is needed to determine which combination of health professionals and interventions is most impactful in practice.
Cost-Effectiveness
According to the CDC, TBC in hypertension management has proven to be cost-effective.54 Systematic reviews and meta-analyses assessing the cost-effectiveness of TBC in hypertension management have been conducted.26,27,29,55-58 While the general consensus supports this approach as being cost-effective, these determinations are based on studies that are widely heterogeneous. In each of these studies, different types of costs are taken into account when determining cost-effectiveness. The range of costs can be quite wide, depending on how they are calculated, making it difficult to determine the true cost-effectiveness of different TBC models.
Intervention cost is represented by the amount of money spent to implement and maintain the intervention beyond the cost of usual care or the cost without the intervention. For TBC, intervention cost consists of personnel resources such as provider time, patient time, and non-personnel resources, including rent and utilities. Studies show that intervention costs for TBC can range from $35 to $1350 per person per year (mean, $618; median, $428).27,56 One analysis, based on 20 studies comparing TBC to usual care, calculated an intervention cost of $284 per person per year,55 while another study showed an intervention cost of $525 per enrollee per year.56 Intervention cost can vary by the type of provider that is used, the amount of time spent per patient, and the setting where services are provided. Overall, the intervention cost of implementing TBC for hypertension management is consistently higher than the cost of usual care.
Health care cost is another factor to consider. It is the difference in the cost of health care products and services that are utilized in the process of TBC, as compared to care that is provided in the absence of TBC. Health care costs include the costs associated with hospitalizations, outpatient visits, emergency room visits, and medications. One study estimated a median health care cost of hypertension TBC of $65 per person per year.55 Overall, studies evaluating the impact of TBC for hypertension management on health care costs were mixed, with some showing that TBC resulted in an increase in health care cost, and others showing a savings compared to usual care.58 The variability in health care costs was due to the different number of health care components and comorbidities of the patients included in the studies. Also, study duration affected the estimated health care costs of TBC. Most studies did not assess long-term health care cost savings that could be achieved from prolonged blood pressure control.58 When considering both intervention and health care cost, Jacob et al estimated that TBC increased overall net cost by a median value of $329 per person per year.55 While some studies did attribute an overall reduction in health care costs to TBC for hypertension management, on average, team-based models increased health care costs compared to usual care.27,29,55,58,59
However, health care costs do not take into account the long-term reductions in morbidity and mortality or increased quality-adjusted life years (QALY) that result from improved blood pressure control attributed to TBC. In most cost-effectiveness studies, an intervention is considered to be cost-effective if the cost per QALY gained is less than the accepted threshold of $50,000.55 One study estimated that the cost per QALY of TBC in hypertension management is $4763,55,60 while another study estimated a median cost per QALY of $9716 to $13,992.55 A systematic review of 34 international studies estimated the median cost per QALY to be $13,986, ranging from $6683 to $58,610.57 The wide range in cost can be attributed to the variability in interventions, health outcomes used to measure effectiveness, and the settings and countries where the studies were conducted. In another study, a TBC intervention involving pharmacists resulted in a cost per QALY of $26,800.61 The intervention was found to be cost-effective for higher-risk patients, defined as those having diabetes, a smoking history, dyslipidemia, or obesity. For patients who did not have these risk factors, the cost per QALY increased to $43,330.61 Thus, the patient population should be considered before implementing a TBC model. Furthermore, the increased use of technology, allowing for more efficient provision of services and communication between providers, could reduce intervention costs and lead to increased cost efficacy in these models.
The variation in the models used for TBC makes it difficult to draw conclusions on the cost-effectiveness of these interventions. Although it is apparent that TBC in general is cost-effective, more studies are needed comparing different team-based models to determine which specific ones are most cost-effective.
Challenges to Implementation of Team-Based Care
Recognizing and addressing the challenges inherent to a TBC approach is important to the sustainability of such a model within various settings and institutions. Numerous studies conducted on team-based models have identified common challenges that appear to be consistent across multiple settings. These challenges can be categorized as financial, provider-specific, and technology.
Financial Barriers
Although studies have demonstrated the cost-effectiveness of controlling hypertension and preventing serious complications, health systems are still confronted with the challenge of covering the cost for TBC implementation and maintenance.29 The 2 main financial barriers for TBC services are stakeholder engagement and reimbursement for services. According to Kennelty et al, stakeholder engagement is key to the sustainability of the service.27 However, decisions by stakeholders on cost are influenced by many factors, which include available funds, perceived value, and estimates for return on investment. Additionally, interventions must align with the organization’s mission and vision and be feasible to implement, and organizations must have the capacity for administrative support.29 These various financial decisions may greatly influence the sustainability of a TBC model.
The reimbursement challenges for individual providers are an additional barrier to the sustainability of the service. In the United States, most providers are reimbursed via fee-for-service payment plans, but these plans do not reimburse all clinical providers because they are not all recognized as licensed providers.62,63 For example, pharmacists are not recognized by the Centers for Medicare & Medicaid Services as licensed health care providers, which limits their ability to be reimbursed for clinical services provided outside of a traditional dispensing role. Furthermore, state laws determine the services nonphysician providers can offer and how they are recognized for reimbursement by tertiary payers. For instance, pharmacist roles, such as ordering labs and modifying or prescribing medication regimens, vary greatly between states.7,63,64
Financial barriers are a major challenge facing the sustainability of a TBC hypertension service, so including all stakeholders in the decision-making process may improve the organization’s ability to sustain the service.
Provider-Specific Barriers
Notable barriers that are attributed to providers include lack of knowledge, lack of time, lack of initiative to change blood pressure medications, and inability to reach intensive blood pressure goals set in guidelines.29 Studies such as the SPRINT trial have significantly impacted clinical guideline cut-offs for blood pressure, but reaching the intensive blood pressure goals from clinical trials is difficult to emulate in clinical practice.65 In a typical clinical setting, providers may lack the confidence to make adjustments in therapy based on a single blood pressure measurement, and clinical inertia, defined as failure of health care providers to modify therapy when indicated,66 may contribute to the inability to achieve blood pressure goals. Many factors contribute to clinical inertia, including lack of knowledge, time, or clinical protocols on how to modify therapy, causing providers to delay clinical decisions. Implementing site-specific protocols and utilizing hypertension specialist health care professionals in TBC can address the barriers contributing to clinical inertia.
Technology Barriers
A common barrier in a variety of services, but especially prevalent in a TBC service, is access to an electronic health record (EHR) for all providers treating the patient. Some providers who are not directly tied to the same clinical site as the patient’s primary care provider may not have adequate access to the full EHR. For example, pharmacists who are managing hypertension in a TBC model in a community pharmacy may have access only to health information from prescription records. Patient interviews may not provide the pharmacist with adequate information about laboratory results, vitals, and other medical information and history for the patient, making it difficult for the pharmacist to make a proper recommendation for treatment.27 Depending on the setting, communication between providers may be a barrier in achieving optimal outcomes, especially when providers do not have access to a shared medical record.
In addition, patients often lack access to technology used to manage hypertension. Many new technologies exist that aid patients in managing their blood pressure, such as smart phone applications to track blood pressure readings and alarms to remind patients to take their medications. Studies have shown that telemonitoring of blood pressure measurements and management of hypertension, especially in combination with TBC, is effective and reduces costs compared to usual care.67 However, the lack of equal access to the various technologies available may inhibit the success of a TBC hypertension program. Patients may lack access, knowledge, or financial means to utilize the various methods available for managing their hypertension electronically.29
Conclusion
Incorporating nonphysician providers into the health care team for the treatment of hypertension has proven to be more effective than usual care and has been recognized by recent guidelines as a best practice approach to achieving blood pressure goals. Multiple studies have demonstrated that TBC utilizing nurses and pharmacists can improve blood pressure management. While adding members to the team increases health care costs, the long-term benefits of achieving optimal blood pressure goals contribute to the overall cost-effectiveness of TBC strategies over usual care. However, comparisons between different TBC models are warranted to determine which combination of health care professionals and/or interventions is most effective. Cost-analysis estimates are difficult to compare due to widely varied methodology and variance in the models that have been employed. Studies must consider pathways to overcoming reimbursement issues, provider-specific challenges, and technology barriers. Follow-up and monitoring after initiation of drug therapy for hypertension control should include systematic strategies to help improve blood pressure, including use of home blood pressure monitoring, TBC, and telehealth strategies. Future implementation science approaches to hypertension TBC models within specific clinic settings will be useful to identify and overcome challenges and will help to determine the populations who will benefit most, allowing for greater success in sustaining TBC models.
Corresponding author: Shawn R. Smith, PharmD, 309 E. 2nd Street, Pomona, CA 91766; shawnsmith@westernu.edu.
Financial disclosures: None.
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69. Casey DE, Thomas RJ, Bhalla V, et al. 2019 AHA/ACC clinical performance and quality measures for adults with high blood pressure: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures. J Am Coll Cardiol. 2019;74:2661-2706.
1. Fryar CD, Ostchega Y, Hales CM, et al. Hypertension prevalence and control among adults: United States, 2015–2016. NCHS Data Brief. 2017(289):1-8.
2. Ambrosius WT, Sink KM, Foy CG, et al. The design and rationale of a multicenter clinical trial comparing two strategies for control of systolic blood pressure: The Systolic Blood Pressure Intervention Trial (SPRINT). Clin Trials. 2014;11:532-546.
3. Lawes CM, Bennett DA, Feigin VL, Rodgers A. Blood pressure and stroke: an overview of published reviews. Stroke. 2017;35:776-785.
4. Zanchetti A, Thomopoulos C, Parati G. Randomized controlled trials of blood pressure lowering in hypertension: A critical reappraisal. Circ Res. 2015;116:1058-1073.
5. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/ AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018;71:e127-e248.
6. Grol R. Successes and failures in the implementation of evidence-based guidelines for clinical practice. Med Care. 2001;39:II46-II54.
7. Brush JE, Handberg EM, Biga C, et al. 2015 ACC health policy statement on cardiovascular team-based care and the role of advanced practice providers. J Am Coll Cardiol. 2015;65:2118-2136.
8. Centers for Disease Control and Prevention. Best practices for cardiovascular disease prevention programs: a guide to effective health care system interventions and community programs linked to clinical services, promoting team-based care to improve high blood pressure control. www.cdc.gov/dhdsp/pubs/guides/best-practices/team-based-care.htm. Accessed April 30, 2020.
9. Centers for Disease Control and Prevention. Task Force recommends team-based care for improving blood pressure [press release]. May 15, 2012. www.cdc.gov/media/releases/2012/p0515_bp_control.html
10. Mitchell P, Wynia M, Golden R, et al. Core principles & values of effective team-based health care. 2012. Institute of Medicine, Washington, DC.
11. Campbell SM, Hann M, Hacker J, et al. Identifying predictors of high-quality care in English general practice: observational study. BMJ. 2001;323:784-787.
12. Shojania KG, Ranji SR, McDonald KM, et al. Effects of quality improvement strategies for type 2 diabetes on glycemic control: a meta-regression analysis. JAMA. 2006;296:427-440.
13. Walsh JM, McDonald KM, Shojania KG, et al. Quality improvement strategies for hypertension management: a systematic review. Med Care. 2006;44:646-657.
14. Wagner E. The role of patient care teams in chronic disease management. BMJ. 2000;320:560-572.
15. Coleman K, Reid R. Continuous and team-based healing relationships: improving patient care through teams. In: Phillips KE, Weir V, eds. Safety Net Medical Home Initiative Implementation Guide Series. 2nd ed. Seattle, WA: Qualis Health and The MacColl Center for Health Care Innovation at the Group Health Research Institute; 2013.
16. Sinsky CA, Willard-Grace R, Schutzbank AM, et al. In search of joy in practice: a report of 23 high-functioning primary care practices. Ann Fam Med. 2013;11:272-278
17. Howard J, Etz RS, Crocker JB, et al. Maximizing the patient-centered medical home (PCMH) by choosing words wisely. J Am Board Fam Med. 2016;29:248-253.
18. Solberg LI, Crain AL, Tillema JO, et al. Challenges of medical home transformation reported by 118 patient-centered medical home (PCMH) leaders. J Am Board Fam Med. 2014;27:449-457.
19. Crabtree BF, Chase SM, Wise CG, et al. Evaluation of patient centered medical home practice transformation initiatives. Med Care. 2011;49:10-16.
20. Carter BL. Blood pressure control—implementing a team approach. US Cardiol. 2011;8:108-113.
21. Carter BL, Rogers M, Daly J, et al. The potency of team-based care interventions for hypertension: a meta-analysis. Arch Intern Med. 2009;169:1748-1755.
22. Proia KK, Thota AB, Njie GJ, et al. Team-based care and improved blood pressure control: a community guide systematic review. Am J Prev Med. 2014;47:86-99.
23. Santschi V, Chiolero A, Colosimo AL, et al. Improving blood pressure control through pharmacist interventions: a meta-analysis of randomized controlled trials. J Am Heart Assoc. 2014;3:e000718.
24. Shaw RJ, McDuffie JR, Hendrix CC, et al. Effects of nurse-managed protocols in the outpatient management of adults with chronic conditions: a systematic review and meta-analysis. Ann Intern Med. 2014;161:113-121.
25. Carter BL, Coffey CS, Ardery G, et al. Cluster-randomized trial of a physician/pharmacist collaborative model to improve blood pressure control. Circ Cardiovasc Qual Outcomes. 2015;8:235-243
26. Carter BL, Bosworth HB, Green BB. The hypertension team: the role of the pharmacist, nurse and teamwork in hypertension therapy. J Clin Hypertens. 2012;14:51-65.
27. Kennelty KA, Polgreen LA, Carter BL. Team-based care with pharmacists to improve blood pressure: a review of recent literature. Curr Hypertens Rep. 2018;20:1.
28. Brownstein JN, Chowdhury FM, Norris SL, et al. Effectiveness of community health workers in the care of people with hypertension. Am J Prev Med. 2007;32:435-447.
29. Derington CG, King JB, Bryant KB, et al. Cost-effectiveness and challenges of implementing intensive blood pressure goals and team-based care. Curr Hypertens Rep. 2019;21:91.
30. Mills KT, Obst KM, Shen W, et al. Comparative effectiveness of implementation strategies for blood pressure control in hypertensive patients: a systematic review and meta-analysis. Ann Intern Med. 2018;168:110-120.
31. Clark CE, Smith LFP, Taylor RS, et al. Nurse led interventions to improve control of blood pressure in people with hypertension: systematic review and meta-analysis. BMJ. 2010;341:c3995.
32. Santschi V, Chiolero A, Burnand B, et al. Impact of pharmacist care in the management of cardiovascular disease risk factors: a systematic review and meta-analysis of randomized trials. Arch Intern Med. 2011;171:1441-1453.
33. Dennison Himmelfarb CR, Commodore-Mensah Y, Hill MN. Expanding the role of nurses to improve hypertension care and control globally. Ann Glob Health. 2016;82:243-253.
34. Clark CE, Smith LFP, Taylor RS, Campbell JL. Nurse-led interventions used to improve control of high blood pressure in people with diabetes: a systematic review and meta-analysis. DiabetMed. 2011;28:250-261.
35. Zhu X, Wong FKY, Wu CLH. Development and evaluation of a nurse-led hypertension management model: A randomized controlled trial. Int J Nurs Stud. 2018;77:171-178.
36. Spruill TM, Williams O, Teresi JA, et al. Comparative effectiveness of home blood pressure telemonitoring (HBPTM) plus nurse case management versus HBPTM alone among Black and Hispanic stroke survivors: study protocol for a randomized controlled trial. Trials. 2015;16:97.
37. Ogedegbe G. Comparative effectiveness of home BP telemonitoring plus nurse case management (HBPTM+NCM) versus HBPTM alone on systolic BP (SBP) reduction among minority stroke survivors. International Stroke Conference 2020; February 19-21, 2020; Los Angeles, CA. Abstract LB19.
38. Dunn SP, Birtcher KK, Beavers CJ, et al. The role of the clinical pharmacist in the care of patients with cardiovascular disease. J Am Coll Cardiol. 2015;66:2129-2139.
39. Santschi V, Chiolero A, Paradis G et al. Pharmacist interventions to improve cardiovascular disease risk factors in diabetes: a systematic review and meta-analysis of randomized controlled trials. Diabetes Care. 2012;35:2706-2717.
40. Anderegg MD, Gums TH, Uribe L, et al. Pharmacist intervention for blood pressure control in patients with diabetes and/or chronic kidney disease. Pharmacotherapy. 2018;38:309-318.
41. Anderegg MD, Gums TH, Uribe L et al. Physician-pharmacist collaborative management: narrowing the socioeconomic blood pressure gap. Hypertension. 2016;68:1314-1320.
42. Sisson EM, Dixon DL, Kildow DC, et al. Effectiveness of a pharmacist-physician team-based collaboration to improve long-term blood pressure control at an inner-city safety-net clinic. Pharmacotherapy. 2016;36:342-347.
43. Dixon DL, Sisson EM, Parod ED, et al. Pharmacist-physician collaborative care model and time to goal blood pressure in the uninsured population. J Clin Hypertens (Greenwich). 2018;20:88-95.
44. Dixon DL, Parod ED, Sisson EM et al. Impact of a pharmacist-physician collaborative care model on time-in-therapeutic blood pressure range in patients with hypertension. J Am Coll Clin Pharm. 2020;3:404-409.
45. Tsuyuki RT, Houle SK, Charrois TL, et al. Randomized trial of the effect of pharmacist prescribing on improving blood pressure in the community: the Alberta Clinical Trial in Optimizing Hypertension (RxACTION). Circulation. 2015;132:93-100.
46. Tsuyuki RT, Al Hamarneh YN, Jones CA, et al. The effectiveness of pharmacist interventions on cardiovascular risk: The Multicenter Randomized Controlled RxEACH trial. J Am Coll Cardiol. 2016;67:2846-2854.
47. Victor RG, Lynch K, Li N, et al. A cluster-randomized trial of blood-pressure reduction in black barbershops. N Engl J Med. 2018;378:1291-1301.
48. Victor RG, Blyler CA, Li N et al. Sustainability of blood pressure reduction in black barbershops. Circulation. 2019;139:10-19.
49. Panattoni L, Hurlimann L, Wilson C, et al. Workflow standardization of a novel team care model to improve chronic care: a quasi-experimental study. BMC Health Serv Res. 2017;17:286.
50. Chang AR, Bonaparte H, Yule C. Randomized controlled trial comparing a self-guided vs. dietitian-led approach using web-based tools to lower blood pressure: study design and rationale. International Stroke Conference 2020; February 19-21, 2020; Los Angeles, CA. Abstract P169.
51. Stephen C, Halcomb E, Mcinnes S, et al. Improving blood pressure control in primary care: The ImPress study. Int J Nurs Stud. 2019;95:28-33.
52. He J, Shi X, Lin M. Comparative effectiveness of implementation strategies on cardiovascular risk factor control in patients with diabetes: The D4C cluster randomized trial. International Stroke Conference 2020; February 19-21, 2020; Los Angeles, CA. Abstract 17.
53. Jafar TH, Gandhi M, de Silva HA, et al. A community-based intervention for managing hypertension in rural South Asia. N Engl J Med. 2020;382:717-726.
54. Centers for Disease Control and Prevention. Promoting team-based care to improve high blood pressure control. www.cdc.gov/dhdsp/pubs/guides/best-practices/team-based-care.htm. Accessed April 30, 2020.
55. Jacob V, Chattopadhyay SK, Thota AB, et al. Economics of team-based care in controlling blood pressure: a community guide systematic review. Am J Prev Med. 2015;49:772-783.
56. Dehmer SP, Baker-Goering MM, Maciosek MV, et al. Modeled health and economic impact of team-based care for hypertension. Am J Prev Med. 2016;50(5 suppl 1):S34-S44.
57. Zhang D, Wang G, Joo H. A systematic review of economic evidence on community hypertension interventions. Am J Prev Med. 2017;53:S121-S130.
58. Community Preventive Services Task Force. Cardiovascular disease: team-based care to improve blood pressure control. 2011. www.thecommunityguide.org/findings/cardiovascular-disease-team-based-care-improve-blood-pressure-control. Accessed April 30, 2020.
59. Kulchaitanaroaj P, Brooks JM, Ardery G et al. Incremental costs associated with physician and pharmacist collaboration to improve blood pressure control. Pharmacotherapy. 2012;32:772-780.
60. Mason JM, Freemantle N, Gibson JM, New JP. Specialist nurse-led clinics to improve control of hypertension and hyperlipidemia in diabetes. Diabetes Care. 2005;28:40-46.
61. Kulchaitanaroaj P, Brooks JM, Chaiyakunapruk N et al. Cost-utility analysis of physician-pharmacist collaborative intervention for treating hypertension compared with usual care. J Hypertens. 2017;35:178-187.
62. Lall D, Engel N, Devadasan N, et al. Models of care for chronic conditions in low/middle-income countries: a ‘best fit’ framework synthesis. BMJ Glob Health. 2018;3:e001077.
63. Bodenheimer T, Chen E, Bennett HD. Confronting the growing burden of chronic disease: can the U.S. health care workforce do the job? Health Aff (Millwood). 2009;28:64-74.
64. Smith M, Bates DW, Bodenheimer T, Cleary PD. Why pharmacists belong in the medical home. Health Aff (Millwood). 2010;29:906-913.
65. Wright JT, Williamson JD, Whelton PK, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373:2103-2116.
66. Phillips LS, Branch WT, Cook CB, et al. Clinical inertia. Ann Intern Med. 2001;135:825-834.
67. McManus RJ, Mant J, Franssen M, et al. Efficacy of self-monitored blood pressure, with or without telemonitoring, for titration of antihypertensive medication (TASMINH4): an unmasked randomised controlled trial. Lancet. 2018;391:949-959.
68. Tucker KL, Sheppard JP, Stevens R, et al. Self-monitoring of blood pressure in hypertension: a systematic review and individual patient data meta-analysis. PLoS Med. 2017;14:e1002389.
69. Casey DE, Thomas RJ, Bhalla V, et al. 2019 AHA/ACC clinical performance and quality measures for adults with high blood pressure: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures. J Am Coll Cardiol. 2019;74:2661-2706.
Timing of Surgery in Patients With Asymptomatic Severe Aortic Stenosis
Study Overview
Objective. To determine the timing of surgical intervention in asymptomatic patients with severe aortic stenosis.
Design. Open-label, multicenter, randomized controlled study.
Setting and participants. A total of 145 asymptomatic patients with very severe aortic stenosis were randomly assigned to early surgery or conservative care.
Main outcome measures. The primary endpoint was a composite of operative mortality or death from a cardiovascular cause during follow-up. The major secondary endpoint was death from any cause during follow-up.
Main results. The primary endpoint occurred in 1 of 73 patients (1%) in the early surgery group and 11 of 72 patients (15%) in the conservative care group (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.01-0.67, P = 0.003). The secondary endpoint occurred in 7% of patients in the early surgery group and 21% of patients in the conservative care group (HR, 0.33; 95% CI, 0.12-0.90).
Conclusion. Among asymptomatic patients with very severe aortic stenosis, the incidence of the composite of operative mortality or death from cardiovascular causes during follow-up was significantly lower among those who underwent early valve replacement surgery compared to those who received conservative care.
Commentary
Aortic stenosis is a progressive disease that can lead to angina, heart failure, and death.1A higher mortality rate is reported in patients with symptomatic aortic stenosis, as compared to patients with asymptomatic disease, and current guidelines require symptoms to be present in order to proceed with aortic valve replacement.2 Management of asymptomatic patients is often determined by the treating physician, with treatment decisions based on multiple factors, such as left ventricular function, stress test results, and the local level of expertise for surgery.2
In this context, the RECOVERY investigators report the findings of their well-designed randomized controlled study assessing patients with asymptomatic severe aortic stenosis, which was defined as aortic valve area ≤ 0.75 cm2 and either transvalvular velocity > 4.5 m/s or a mean gradient ≥ 50 mm Hg. Compared to patients who received conservative care, patients who underwent early valve surgery had a significantly lower rate of a composite of operative mortality or death from any cardiovascular causes during follow-up. Notably, the number needed to treat to prevent 1 death from cardiovascular causes within 4 years was 20.
The strengths of this trial include complete long-term follow-up (> 4 years) and low cross-over rates. Furthermore, as the study targeted a previously understudied population, there were a number of interesting observations, in addition to the primary endpoint. First, the risk of sudden death was high in patients who received conservative care, 4% at 4 years and 14% at 8 years, a finding contrary to the common belief that asymptomatic patients are at lower risk of sudden cardiac death. Second, 74% of patients assigned to initial conservative care required aortic valve replacement during the follow-up period. Furthermore, when the patients assigned to conservative care required surgery, it was often performed emergently (17%), which could have contributed to the higher mortality in this group of patients. Finally, hospitalization for heart failure was more common in patients randomized to conservative care compared to patients with early surgery. These findings will help physicians conduct detailed, informed discussions with their patients regarding the risks/benefits of early surgery versus conservative management.
There are a few limitations of the RECOVERY trial to consider. First, this study investigated the effect of surgical aortic valve replacement; whether its findings can be extended to transcatheter aortic valve replacement (TAVR) requires further investigation. Patients who were enrolled in this study were younger and had fewer comorbidities than typical patients referred for TAVR. Second, all patients included in this study had the most severe form of aortic stenosis (valve area ≤ 0.75 cm2 with either a peak velocity of ≥ 4.5 m/s or mean gradient ≥ 50 mm Hg). Finally, the study was performed in highly experienced centers, as evidenced by a very low (0%) mortality rate after aortic valve replacement. Therefore, the finding may not be applicable to centers that have less experience with aortic valve replacement surgery.
Applications for Clinical Practice
The findings of the RECOVERY trial strongly suggest a mortality benefit of early surgery compared to conservative management in patients with asymptomatic severe aortic stenosis.
–Taishi Hirai, MD
1. Otto CM, Prendergast B. Aortic-valve stenosis--from patients at risk to severe valve obstruction. N Engl J Med. 2014;371:744-756.
2. Nishimura RA, Otto CM, Bonow RO, et al. 2017 AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2017;135:e1159-e1195.
Study Overview
Objective. To determine the timing of surgical intervention in asymptomatic patients with severe aortic stenosis.
Design. Open-label, multicenter, randomized controlled study.
Setting and participants. A total of 145 asymptomatic patients with very severe aortic stenosis were randomly assigned to early surgery or conservative care.
Main outcome measures. The primary endpoint was a composite of operative mortality or death from a cardiovascular cause during follow-up. The major secondary endpoint was death from any cause during follow-up.
Main results. The primary endpoint occurred in 1 of 73 patients (1%) in the early surgery group and 11 of 72 patients (15%) in the conservative care group (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.01-0.67, P = 0.003). The secondary endpoint occurred in 7% of patients in the early surgery group and 21% of patients in the conservative care group (HR, 0.33; 95% CI, 0.12-0.90).
Conclusion. Among asymptomatic patients with very severe aortic stenosis, the incidence of the composite of operative mortality or death from cardiovascular causes during follow-up was significantly lower among those who underwent early valve replacement surgery compared to those who received conservative care.
Commentary
Aortic stenosis is a progressive disease that can lead to angina, heart failure, and death.1A higher mortality rate is reported in patients with symptomatic aortic stenosis, as compared to patients with asymptomatic disease, and current guidelines require symptoms to be present in order to proceed with aortic valve replacement.2 Management of asymptomatic patients is often determined by the treating physician, with treatment decisions based on multiple factors, such as left ventricular function, stress test results, and the local level of expertise for surgery.2
In this context, the RECOVERY investigators report the findings of their well-designed randomized controlled study assessing patients with asymptomatic severe aortic stenosis, which was defined as aortic valve area ≤ 0.75 cm2 and either transvalvular velocity > 4.5 m/s or a mean gradient ≥ 50 mm Hg. Compared to patients who received conservative care, patients who underwent early valve surgery had a significantly lower rate of a composite of operative mortality or death from any cardiovascular causes during follow-up. Notably, the number needed to treat to prevent 1 death from cardiovascular causes within 4 years was 20.
The strengths of this trial include complete long-term follow-up (> 4 years) and low cross-over rates. Furthermore, as the study targeted a previously understudied population, there were a number of interesting observations, in addition to the primary endpoint. First, the risk of sudden death was high in patients who received conservative care, 4% at 4 years and 14% at 8 years, a finding contrary to the common belief that asymptomatic patients are at lower risk of sudden cardiac death. Second, 74% of patients assigned to initial conservative care required aortic valve replacement during the follow-up period. Furthermore, when the patients assigned to conservative care required surgery, it was often performed emergently (17%), which could have contributed to the higher mortality in this group of patients. Finally, hospitalization for heart failure was more common in patients randomized to conservative care compared to patients with early surgery. These findings will help physicians conduct detailed, informed discussions with their patients regarding the risks/benefits of early surgery versus conservative management.
There are a few limitations of the RECOVERY trial to consider. First, this study investigated the effect of surgical aortic valve replacement; whether its findings can be extended to transcatheter aortic valve replacement (TAVR) requires further investigation. Patients who were enrolled in this study were younger and had fewer comorbidities than typical patients referred for TAVR. Second, all patients included in this study had the most severe form of aortic stenosis (valve area ≤ 0.75 cm2 with either a peak velocity of ≥ 4.5 m/s or mean gradient ≥ 50 mm Hg). Finally, the study was performed in highly experienced centers, as evidenced by a very low (0%) mortality rate after aortic valve replacement. Therefore, the finding may not be applicable to centers that have less experience with aortic valve replacement surgery.
Applications for Clinical Practice
The findings of the RECOVERY trial strongly suggest a mortality benefit of early surgery compared to conservative management in patients with asymptomatic severe aortic stenosis.
–Taishi Hirai, MD
Study Overview
Objective. To determine the timing of surgical intervention in asymptomatic patients with severe aortic stenosis.
Design. Open-label, multicenter, randomized controlled study.
Setting and participants. A total of 145 asymptomatic patients with very severe aortic stenosis were randomly assigned to early surgery or conservative care.
Main outcome measures. The primary endpoint was a composite of operative mortality or death from a cardiovascular cause during follow-up. The major secondary endpoint was death from any cause during follow-up.
Main results. The primary endpoint occurred in 1 of 73 patients (1%) in the early surgery group and 11 of 72 patients (15%) in the conservative care group (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.01-0.67, P = 0.003). The secondary endpoint occurred in 7% of patients in the early surgery group and 21% of patients in the conservative care group (HR, 0.33; 95% CI, 0.12-0.90).
Conclusion. Among asymptomatic patients with very severe aortic stenosis, the incidence of the composite of operative mortality or death from cardiovascular causes during follow-up was significantly lower among those who underwent early valve replacement surgery compared to those who received conservative care.
Commentary
Aortic stenosis is a progressive disease that can lead to angina, heart failure, and death.1A higher mortality rate is reported in patients with symptomatic aortic stenosis, as compared to patients with asymptomatic disease, and current guidelines require symptoms to be present in order to proceed with aortic valve replacement.2 Management of asymptomatic patients is often determined by the treating physician, with treatment decisions based on multiple factors, such as left ventricular function, stress test results, and the local level of expertise for surgery.2
In this context, the RECOVERY investigators report the findings of their well-designed randomized controlled study assessing patients with asymptomatic severe aortic stenosis, which was defined as aortic valve area ≤ 0.75 cm2 and either transvalvular velocity > 4.5 m/s or a mean gradient ≥ 50 mm Hg. Compared to patients who received conservative care, patients who underwent early valve surgery had a significantly lower rate of a composite of operative mortality or death from any cardiovascular causes during follow-up. Notably, the number needed to treat to prevent 1 death from cardiovascular causes within 4 years was 20.
The strengths of this trial include complete long-term follow-up (> 4 years) and low cross-over rates. Furthermore, as the study targeted a previously understudied population, there were a number of interesting observations, in addition to the primary endpoint. First, the risk of sudden death was high in patients who received conservative care, 4% at 4 years and 14% at 8 years, a finding contrary to the common belief that asymptomatic patients are at lower risk of sudden cardiac death. Second, 74% of patients assigned to initial conservative care required aortic valve replacement during the follow-up period. Furthermore, when the patients assigned to conservative care required surgery, it was often performed emergently (17%), which could have contributed to the higher mortality in this group of patients. Finally, hospitalization for heart failure was more common in patients randomized to conservative care compared to patients with early surgery. These findings will help physicians conduct detailed, informed discussions with their patients regarding the risks/benefits of early surgery versus conservative management.
There are a few limitations of the RECOVERY trial to consider. First, this study investigated the effect of surgical aortic valve replacement; whether its findings can be extended to transcatheter aortic valve replacement (TAVR) requires further investigation. Patients who were enrolled in this study were younger and had fewer comorbidities than typical patients referred for TAVR. Second, all patients included in this study had the most severe form of aortic stenosis (valve area ≤ 0.75 cm2 with either a peak velocity of ≥ 4.5 m/s or mean gradient ≥ 50 mm Hg). Finally, the study was performed in highly experienced centers, as evidenced by a very low (0%) mortality rate after aortic valve replacement. Therefore, the finding may not be applicable to centers that have less experience with aortic valve replacement surgery.
Applications for Clinical Practice
The findings of the RECOVERY trial strongly suggest a mortality benefit of early surgery compared to conservative management in patients with asymptomatic severe aortic stenosis.
–Taishi Hirai, MD
1. Otto CM, Prendergast B. Aortic-valve stenosis--from patients at risk to severe valve obstruction. N Engl J Med. 2014;371:744-756.
2. Nishimura RA, Otto CM, Bonow RO, et al. 2017 AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2017;135:e1159-e1195.
1. Otto CM, Prendergast B. Aortic-valve stenosis--from patients at risk to severe valve obstruction. N Engl J Med. 2014;371:744-756.
2. Nishimura RA, Otto CM, Bonow RO, et al. 2017 AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2017;135:e1159-e1195.
Today’s top news highlights: ACE inhibitors in COVID patients, fewer AMI admissions, and more
Here are the stories our MDedge editors across specialties think you need to know about today:
Are ACE inhibitors protective in COVID-19?
Older patients with COVID-19 had a lower risk of developing severe illness if they were taking ACE inhibitors, according to a large observational U.S. study. ACE inhibitor use was associated with an almost 40% lower risk for COVID-19 hospitalization for older people enrolled in Medicare Advantage plans. Senior investigator Harlan M. Krumholz, MD, said that while he and his associates think this finding is worthy of further study, “We don’t believe this is enough info to change practice.” The study was published on the MedRxiv preprint server and has not yet been peer reviewed.
READ MORE.
AMI: Admissions drop, deaths rise
In Italy, sharp nationwide decreases in hospitalizations for acute myocardial infarctions (AMIs) during the height of COVID-19 were offset by higher mortality for patients who did present. The study counted AMIs at 54 hospitals nationwide for the week of March 12-19, 2020, and compared that with an equivalent week in 2019 – 319 vs. 618 AMIs, respectively, representing a 48% reduction in hospitalizations. Mortality for ST-segment elevation MI cases more than tripled to 14% during the outbreak, compared with 4% in 2019. “The concern is fewer MIs most likely means people are dying at home or presenting later as this study suggests,” commented Martha Gulati, MD, chief of cardiology at the University of Arizona, Phoenix, who was not involved with the study.
READ MORE.
Prenatal, postpartum screening for depression falls short
Health care providers fail to ask one in five prenatal patients and one in eight postpartum patients about depression, according to the Centers for Disease Control and Prevention. Researchers analyzed self-reported data on postpartum depressive symptoms collected in 2018 by the Pregnancy Risk Assessment Monitoring System. Mental health conditions play a role in approximately 9% of pregnancy-related deaths and not asking about depression represents “missed opportunities to potentially identify and treat women with depression,” said coauthor Jean Y. Ko, PhD, from the division of reproductive health at the National Center for Chronic Disease Prevention and Health Promotion.
For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.
Here are the stories our MDedge editors across specialties think you need to know about today:
Are ACE inhibitors protective in COVID-19?
Older patients with COVID-19 had a lower risk of developing severe illness if they were taking ACE inhibitors, according to a large observational U.S. study. ACE inhibitor use was associated with an almost 40% lower risk for COVID-19 hospitalization for older people enrolled in Medicare Advantage plans. Senior investigator Harlan M. Krumholz, MD, said that while he and his associates think this finding is worthy of further study, “We don’t believe this is enough info to change practice.” The study was published on the MedRxiv preprint server and has not yet been peer reviewed.
READ MORE.
AMI: Admissions drop, deaths rise
In Italy, sharp nationwide decreases in hospitalizations for acute myocardial infarctions (AMIs) during the height of COVID-19 were offset by higher mortality for patients who did present. The study counted AMIs at 54 hospitals nationwide for the week of March 12-19, 2020, and compared that with an equivalent week in 2019 – 319 vs. 618 AMIs, respectively, representing a 48% reduction in hospitalizations. Mortality for ST-segment elevation MI cases more than tripled to 14% during the outbreak, compared with 4% in 2019. “The concern is fewer MIs most likely means people are dying at home or presenting later as this study suggests,” commented Martha Gulati, MD, chief of cardiology at the University of Arizona, Phoenix, who was not involved with the study.
READ MORE.
Prenatal, postpartum screening for depression falls short
Health care providers fail to ask one in five prenatal patients and one in eight postpartum patients about depression, according to the Centers for Disease Control and Prevention. Researchers analyzed self-reported data on postpartum depressive symptoms collected in 2018 by the Pregnancy Risk Assessment Monitoring System. Mental health conditions play a role in approximately 9% of pregnancy-related deaths and not asking about depression represents “missed opportunities to potentially identify and treat women with depression,” said coauthor Jean Y. Ko, PhD, from the division of reproductive health at the National Center for Chronic Disease Prevention and Health Promotion.
For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.
Here are the stories our MDedge editors across specialties think you need to know about today:
Are ACE inhibitors protective in COVID-19?
Older patients with COVID-19 had a lower risk of developing severe illness if they were taking ACE inhibitors, according to a large observational U.S. study. ACE inhibitor use was associated with an almost 40% lower risk for COVID-19 hospitalization for older people enrolled in Medicare Advantage plans. Senior investigator Harlan M. Krumholz, MD, said that while he and his associates think this finding is worthy of further study, “We don’t believe this is enough info to change practice.” The study was published on the MedRxiv preprint server and has not yet been peer reviewed.
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AMI: Admissions drop, deaths rise
In Italy, sharp nationwide decreases in hospitalizations for acute myocardial infarctions (AMIs) during the height of COVID-19 were offset by higher mortality for patients who did present. The study counted AMIs at 54 hospitals nationwide for the week of March 12-19, 2020, and compared that with an equivalent week in 2019 – 319 vs. 618 AMIs, respectively, representing a 48% reduction in hospitalizations. Mortality for ST-segment elevation MI cases more than tripled to 14% during the outbreak, compared with 4% in 2019. “The concern is fewer MIs most likely means people are dying at home or presenting later as this study suggests,” commented Martha Gulati, MD, chief of cardiology at the University of Arizona, Phoenix, who was not involved with the study.
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Prenatal, postpartum screening for depression falls short
Health care providers fail to ask one in five prenatal patients and one in eight postpartum patients about depression, according to the Centers for Disease Control and Prevention. Researchers analyzed self-reported data on postpartum depressive symptoms collected in 2018 by the Pregnancy Risk Assessment Monitoring System. Mental health conditions play a role in approximately 9% of pregnancy-related deaths and not asking about depression represents “missed opportunities to potentially identify and treat women with depression,” said coauthor Jean Y. Ko, PhD, from the division of reproductive health at the National Center for Chronic Disease Prevention and Health Promotion.
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