Anticoagulation Hub

MUNICH – Many patients with diabetes who could benefit from low-dose aspirin therapy may not be getting it – and many who are getting aspirin should not be, according to data presented at the annual meeting of the European Association for the Study of Diabetes.

A large, randomized trial concluded that 21% of diabetes patients who qualified for aspirin therapy for cardiovascular risk reduction were not getting it, and that it was contraindicated in almost 60% of those who were taking it, Lauren Crain, PhD, reported at the meeting.

Balancing the risks and benefits of aspirin therapy is not an easy challenge, said Dr. Crain, a health behavior researcher at HealthPartners Institute, Minneapolis. The clinical information necessary for the assessment is “rather lengthy, and not always readily available in primary care settings,” she said, and it’s clear from this study that clinicians could use some help in this area. Unfortunately, the electronic algorithm tested, which was meant to improve appropriate aspirin prescribing, didn’t improve the situation very much.

“At the final visit in the diabetes group [after the algorithm was employed], the total proportion of patients using aspirin was higher than at the first visit,” Dr. Crain noted. “However, that was the case regardless of whether patients were over- or underusing aspirin at the first visit.”

The aspirin findings were part of a large, randomized trial testing the algorithm as a way to reduce cardiovascular risk factors. The study was conducted in 19 primary care practices.

The decision-making algorithm, Cardiovascular Wizard, uses electronic health records to identify and advise patients with uncontrolled cardiovascular risk factors. Priorities and clinical recommendations are displayed for the provider and patient in the hope of facilitating shared decision making, Dr. Crain said.

One of the Wizard’s algorithms concerns aspirin prescribing. It is programmed with data from the United States Preventive Services Task Force, and recommends aspirin if cardiovascular risk scores are high and if consistent with providing a benefit greater than the risk of gastrointestinal bleeding. Aspirin is not recommended if the benefit is determined to be low or if major contraindications are present, including anticoagulant use or history of intracerebral hemorrhage.

The tool also alerts providers to the presence of other potential risks including aspirin allergy or intolerance, history of GI bleeds or risk conditions, and the concomitant use of nonsteroidal anti-inflammatory drugs.

The study comprised 11,000 adults, 4,000 of whom had diabetes. The remainder had high-risk, reversible cardiovascular risk factors (hypertension, dyslipidemia, or tobacco use). Each group was randomized to either cardiovascular risk assessment by usual care or with the Cardiovascular Wizard program.

The aspirin substudy looked at aspirin use at the baseline visit and the patient’s final, 1-year follow-up visit. At both visits, aspirin use was documented, and the clinician used the Wizard to assess whether or not it was indicated.

At the baseline visit, 71% of the diabetes group was using aspirin. However, according to the Wizard tool, more than one-third of them should not have been taking it – and among these, 57% were doing so. Among the remaining two-thirds of patients, all of whom should have been using aspirin, 21% were not taking it, Dr. Crain said.

Among the patients with reversible high-risk factors, 27% were using aspirin. However, according to the Wizard tool, the drug was contraindicated in 34% of those patients. “Most importantly, however, among those for whom aspirin was indicated, only 25% were using it – so, we’re talking about a 75% underusage,” Dr. Crain said.

By the 1-year follow-up visit, the situation was not much changed, despite the tool’s recommendations. Among those with diabetes, 56% in the usual care group and 60% in Wizard group were still overusing aspirin. Underuse was occurring in 21% of the usual care group and 17% of the Wizard group.

Patients with reversible high-risk factors fared a little better at 1 year, especially those who, at baseline, should have been taking aspirin but were not. Among these, 10% in the usual care group and 13% in the Wizard group had started taking aspirin.

The results were a bit of a disappointment, Dr. Crain said, but they don’t invalidate the investigators’ faith in an algorithmic advising system.

“We do think that electronic health record tools like this can help providers follow guidelines and improve the quality of their aspirin recommendations and prescribing, and hopefully reduce cardiovascular events and aspirin-related hazards,” she said. “Unfortunately, that didn’t happen here in the diabetes patients,” and the results in the second group were not stellar.

She added that the Wizard development team will be tweaking the tool to clarify some of the choices available as it guides patients and providers through the algorithm, in hopes of improving its efficacy.

Dr. Crain made no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

MUNICH – Many patients with diabetes who could benefit from low-dose aspirin therapy may not be getting it – and many who are getting aspirin should not be, according to data presented at the annual meeting of the European Association for the Study of Diabetes.

A large, randomized trial concluded that 21% of diabetes patients who qualified for aspirin therapy for cardiovascular risk reduction were not getting it, and that it was contraindicated in almost 60% of those who were taking it, Lauren Crain, PhD, reported at the meeting.

Balancing the risks and benefits of aspirin therapy is not an easy challenge, said Dr. Crain, a health behavior researcher at HealthPartners Institute, Minneapolis. The clinical information necessary for the assessment is “rather lengthy, and not always readily available in primary care settings,” she said, and it’s clear from this study that clinicians could use some help in this area. Unfortunately, the electronic algorithm tested, which was meant to improve appropriate aspirin prescribing, didn’t improve the situation very much.

“At the final visit in the diabetes group [after the algorithm was employed], the total proportion of patients using aspirin was higher than at the first visit,” Dr. Crain noted. “However, that was the case regardless of whether patients were over- or underusing aspirin at the first visit.”

The aspirin findings were part of a large, randomized trial testing the algorithm as a way to reduce cardiovascular risk factors. The study was conducted in 19 primary care practices.

The decision-making algorithm, Cardiovascular Wizard, uses electronic health records to identify and advise patients with uncontrolled cardiovascular risk factors. Priorities and clinical recommendations are displayed for the provider and patient in the hope of facilitating shared decision making, Dr. Crain said.

One of the Wizard’s algorithms concerns aspirin prescribing. It is programmed with data from the United States Preventive Services Task Force, and recommends aspirin if cardiovascular risk scores are high and if consistent with providing a benefit greater than the risk of gastrointestinal bleeding. Aspirin is not recommended if the benefit is determined to be low or if major contraindications are present, including anticoagulant use or history of intracerebral hemorrhage.

The tool also alerts providers to the presence of other potential risks including aspirin allergy or intolerance, history of GI bleeds or risk conditions, and the concomitant use of nonsteroidal anti-inflammatory drugs.

The study comprised 11,000 adults, 4,000 of whom had diabetes. The remainder had high-risk, reversible cardiovascular risk factors (hypertension, dyslipidemia, or tobacco use). Each group was randomized to either cardiovascular risk assessment by usual care or with the Cardiovascular Wizard program.

The aspirin substudy looked at aspirin use at the baseline visit and the patient’s final, 1-year follow-up visit. At both visits, aspirin use was documented, and the clinician used the Wizard to assess whether or not it was indicated.

At the baseline visit, 71% of the diabetes group was using aspirin. However, according to the Wizard tool, more than one-third of them should not have been taking it – and among these, 57% were doing so. Among the remaining two-thirds of patients, all of whom should have been using aspirin, 21% were not taking it, Dr. Crain said.

Among the patients with reversible high-risk factors, 27% were using aspirin. However, according to the Wizard tool, the drug was contraindicated in 34% of those patients. “Most importantly, however, among those for whom aspirin was indicated, only 25% were using it – so, we’re talking about a 75% underusage,” Dr. Crain said.

By the 1-year follow-up visit, the situation was not much changed, despite the tool’s recommendations. Among those with diabetes, 56% in the usual care group and 60% in Wizard group were still overusing aspirin. Underuse was occurring in 21% of the usual care group and 17% of the Wizard group.

Patients with reversible high-risk factors fared a little better at 1 year, especially those who, at baseline, should have been taking aspirin but were not. Among these, 10% in the usual care group and 13% in the Wizard group had started taking aspirin.

The results were a bit of a disappointment, Dr. Crain said, but they don’t invalidate the investigators’ faith in an algorithmic advising system.

“We do think that electronic health record tools like this can help providers follow guidelines and improve the quality of their aspirin recommendations and prescribing, and hopefully reduce cardiovascular events and aspirin-related hazards,” she said. “Unfortunately, that didn’t happen here in the diabetes patients,” and the results in the second group were not stellar.

She added that the Wizard development team will be tweaking the tool to clarify some of the choices available as it guides patients and providers through the algorithm, in hopes of improving its efficacy.

Dr. Crain made no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

MUNICH – Many patients with diabetes who could benefit from low-dose aspirin therapy may not be getting it – and many who are getting aspirin should not be, according to data presented at the annual meeting of the European Association for the Study of Diabetes.

A large, randomized trial concluded that 21% of diabetes patients who qualified for aspirin therapy for cardiovascular risk reduction were not getting it, and that it was contraindicated in almost 60% of those who were taking it, Lauren Crain, PhD, reported at the meeting.

Balancing the risks and benefits of aspirin therapy is not an easy challenge, said Dr. Crain, a health behavior researcher at HealthPartners Institute, Minneapolis. The clinical information necessary for the assessment is “rather lengthy, and not always readily available in primary care settings,” she said, and it’s clear from this study that clinicians could use some help in this area. Unfortunately, the electronic algorithm tested, which was meant to improve appropriate aspirin prescribing, didn’t improve the situation very much.

“At the final visit in the diabetes group [after the algorithm was employed], the total proportion of patients using aspirin was higher than at the first visit,” Dr. Crain noted. “However, that was the case regardless of whether patients were over- or underusing aspirin at the first visit.”

The aspirin findings were part of a large, randomized trial testing the algorithm as a way to reduce cardiovascular risk factors. The study was conducted in 19 primary care practices.

The decision-making algorithm, Cardiovascular Wizard, uses electronic health records to identify and advise patients with uncontrolled cardiovascular risk factors. Priorities and clinical recommendations are displayed for the provider and patient in the hope of facilitating shared decision making, Dr. Crain said.

One of the Wizard’s algorithms concerns aspirin prescribing. It is programmed with data from the United States Preventive Services Task Force, and recommends aspirin if cardiovascular risk scores are high and if consistent with providing a benefit greater than the risk of gastrointestinal bleeding. Aspirin is not recommended if the benefit is determined to be low or if major contraindications are present, including anticoagulant use or history of intracerebral hemorrhage.

The tool also alerts providers to the presence of other potential risks including aspirin allergy or intolerance, history of GI bleeds or risk conditions, and the concomitant use of nonsteroidal anti-inflammatory drugs.

The study comprised 11,000 adults, 4,000 of whom had diabetes. The remainder had high-risk, reversible cardiovascular risk factors (hypertension, dyslipidemia, or tobacco use). Each group was randomized to either cardiovascular risk assessment by usual care or with the Cardiovascular Wizard program.

The aspirin substudy looked at aspirin use at the baseline visit and the patient’s final, 1-year follow-up visit. At both visits, aspirin use was documented, and the clinician used the Wizard to assess whether or not it was indicated.

At the baseline visit, 71% of the diabetes group was using aspirin. However, according to the Wizard tool, more than one-third of them should not have been taking it – and among these, 57% were doing so. Among the remaining two-thirds of patients, all of whom should have been using aspirin, 21% were not taking it, Dr. Crain said.

Among the patients with reversible high-risk factors, 27% were using aspirin. However, according to the Wizard tool, the drug was contraindicated in 34% of those patients. “Most importantly, however, among those for whom aspirin was indicated, only 25% were using it – so, we’re talking about a 75% underusage,” Dr. Crain said.

By the 1-year follow-up visit, the situation was not much changed, despite the tool’s recommendations. Among those with diabetes, 56% in the usual care group and 60% in Wizard group were still overusing aspirin. Underuse was occurring in 21% of the usual care group and 17% of the Wizard group.

Patients with reversible high-risk factors fared a little better at 1 year, especially those who, at baseline, should have been taking aspirin but were not. Among these, 10% in the usual care group and 13% in the Wizard group had started taking aspirin.

The results were a bit of a disappointment, Dr. Crain said, but they don’t invalidate the investigators’ faith in an algorithmic advising system.

“We do think that electronic health record tools like this can help providers follow guidelines and improve the quality of their aspirin recommendations and prescribing, and hopefully reduce cardiovascular events and aspirin-related hazards,” she said. “Unfortunately, that didn’t happen here in the diabetes patients,” and the results in the second group were not stellar.

She added that the Wizard development team will be tweaking the tool to clarify some of the choices available as it guides patients and providers through the algorithm, in hopes of improving its efficacy.

Dr. Crain made no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

For patients with large-vessel ischemic stroke, endovascular thrombectomy produces better functional outcomes at 90 days than does optimal medical therapy, as long as the procedure is started within 7.3 hours of symptom onset, according to a report published online Sept. 27 in JAMA.

The benefit of thrombectomy was greatest when the procedure was begun under 2 hours from symptom onset, and it became nonsignificant after 7 hours and 18 minutes elapsed. This emphasizes “the importance of programs to enhance patient awareness, out-of-hospital care, and in-hospital management to shorten symptom onset-to-treatment times,” wrote Jeffrey L. Saver, MD, of the University of California, Los Angeles, and his associates.

Five major randomized trials have demonstrated the benefit of second-generation endovascular recanalization therapies over medical therapy in this patient population, but uncertainties persist regarding the timing of the intervention. For example, practice guidelines in the United States recommend thrombectomy until 6 hours after symptom onset, but the Food and Drug Administration allows thrombectomy devices to be used up to 8 hours after symptom onset and Canadian guidelines recommend the procedure for selected patients up to 12 hours after symptom onset.

The investigators for the five trials formed the Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials (HERMES) collaboration to pool their individual patient data and perform a meta-analysis to clarify the issue of timing. They assessed patients’ functional independence at 90 days using the modified Rankin Score (mRS). The study participants included 634 patients who had been randomly assigned to endovascular thrombectomy and 653 randomly assigned to medical therapy.

The intervention correlated with a substantially lower degree of patient disability at 90 days than did medical therapy: the mean mRS was 2.9 in the thrombectomy group and 3.6 in the medical therapy group. In addition, increasing delays in treatment were associated with higher levels of residual disability in the thrombectomy group but not in the medical therapy group, the investigators reported.

“Based on the current study, and assuming the findings are generalizable to the population of patients with acute ischemic stroke due to large-vessel occlusion, among every 1,000 patients achieving substantial endovascular reperfusion, for every 15-minute faster ED door-to-reperfusion time, an estimated 39 patients would have a less-disabled outcome at 3 months, including 25 more who would achieve functional independence (mRS 0-2),” Dr. Saver and his associates wrote (JAMA. 2016;316[12]:1279-88).

These findings reinforce current recommendations to attempt endovascular thrombectomy when the procedure can be initiated within 6 hours of symptom onset, and they also “provide evidence that potentially supports strengthening of the recommendation for treatment from 6 through 7.3 hours after symptom onset,” they added.

No specific sponsor of this study was cited. Dr. Saver reported ties to Medtronic, Stryker, Cognition Medical, Covidien, Neuravi, BrainsGate, Pfizer, Bristol-Myers Squibb, Boehringer Ingelheim, ZZ Biotech, St. Jude Medical, and Genentech. His associates reported ties to numerous industry sources.

For patients with large-vessel ischemic stroke, endovascular thrombectomy produces better functional outcomes at 90 days than does optimal medical therapy, as long as the procedure is started within 7.3 hours of symptom onset, according to a report published online Sept. 27 in JAMA.

The benefit of thrombectomy was greatest when the procedure was begun under 2 hours from symptom onset, and it became nonsignificant after 7 hours and 18 minutes elapsed. This emphasizes “the importance of programs to enhance patient awareness, out-of-hospital care, and in-hospital management to shorten symptom onset-to-treatment times,” wrote Jeffrey L. Saver, MD, of the University of California, Los Angeles, and his associates.

Five major randomized trials have demonstrated the benefit of second-generation endovascular recanalization therapies over medical therapy in this patient population, but uncertainties persist regarding the timing of the intervention. For example, practice guidelines in the United States recommend thrombectomy until 6 hours after symptom onset, but the Food and Drug Administration allows thrombectomy devices to be used up to 8 hours after symptom onset and Canadian guidelines recommend the procedure for selected patients up to 12 hours after symptom onset.

The investigators for the five trials formed the Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials (HERMES) collaboration to pool their individual patient data and perform a meta-analysis to clarify the issue of timing. They assessed patients’ functional independence at 90 days using the modified Rankin Score (mRS). The study participants included 634 patients who had been randomly assigned to endovascular thrombectomy and 653 randomly assigned to medical therapy.

The intervention correlated with a substantially lower degree of patient disability at 90 days than did medical therapy: the mean mRS was 2.9 in the thrombectomy group and 3.6 in the medical therapy group. In addition, increasing delays in treatment were associated with higher levels of residual disability in the thrombectomy group but not in the medical therapy group, the investigators reported.

“Based on the current study, and assuming the findings are generalizable to the population of patients with acute ischemic stroke due to large-vessel occlusion, among every 1,000 patients achieving substantial endovascular reperfusion, for every 15-minute faster ED door-to-reperfusion time, an estimated 39 patients would have a less-disabled outcome at 3 months, including 25 more who would achieve functional independence (mRS 0-2),” Dr. Saver and his associates wrote (JAMA. 2016;316[12]:1279-88).

These findings reinforce current recommendations to attempt endovascular thrombectomy when the procedure can be initiated within 6 hours of symptom onset, and they also “provide evidence that potentially supports strengthening of the recommendation for treatment from 6 through 7.3 hours after symptom onset,” they added.

No specific sponsor of this study was cited. Dr. Saver reported ties to Medtronic, Stryker, Cognition Medical, Covidien, Neuravi, BrainsGate, Pfizer, Bristol-Myers Squibb, Boehringer Ingelheim, ZZ Biotech, St. Jude Medical, and Genentech. His associates reported ties to numerous industry sources.

For patients with large-vessel ischemic stroke, endovascular thrombectomy produces better functional outcomes at 90 days than does optimal medical therapy, as long as the procedure is started within 7.3 hours of symptom onset, according to a report published online Sept. 27 in JAMA.

The benefit of thrombectomy was greatest when the procedure was begun under 2 hours from symptom onset, and it became nonsignificant after 7 hours and 18 minutes elapsed. This emphasizes “the importance of programs to enhance patient awareness, out-of-hospital care, and in-hospital management to shorten symptom onset-to-treatment times,” wrote Jeffrey L. Saver, MD, of the University of California, Los Angeles, and his associates.

Five major randomized trials have demonstrated the benefit of second-generation endovascular recanalization therapies over medical therapy in this patient population, but uncertainties persist regarding the timing of the intervention. For example, practice guidelines in the United States recommend thrombectomy until 6 hours after symptom onset, but the Food and Drug Administration allows thrombectomy devices to be used up to 8 hours after symptom onset and Canadian guidelines recommend the procedure for selected patients up to 12 hours after symptom onset.

The investigators for the five trials formed the Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials (HERMES) collaboration to pool their individual patient data and perform a meta-analysis to clarify the issue of timing. They assessed patients’ functional independence at 90 days using the modified Rankin Score (mRS). The study participants included 634 patients who had been randomly assigned to endovascular thrombectomy and 653 randomly assigned to medical therapy.

The intervention correlated with a substantially lower degree of patient disability at 90 days than did medical therapy: the mean mRS was 2.9 in the thrombectomy group and 3.6 in the medical therapy group. In addition, increasing delays in treatment were associated with higher levels of residual disability in the thrombectomy group but not in the medical therapy group, the investigators reported.

“Based on the current study, and assuming the findings are generalizable to the population of patients with acute ischemic stroke due to large-vessel occlusion, among every 1,000 patients achieving substantial endovascular reperfusion, for every 15-minute faster ED door-to-reperfusion time, an estimated 39 patients would have a less-disabled outcome at 3 months, including 25 more who would achieve functional independence (mRS 0-2),” Dr. Saver and his associates wrote (JAMA. 2016;316[12]:1279-88).

These findings reinforce current recommendations to attempt endovascular thrombectomy when the procedure can be initiated within 6 hours of symptom onset, and they also “provide evidence that potentially supports strengthening of the recommendation for treatment from 6 through 7.3 hours after symptom onset,” they added.

No specific sponsor of this study was cited. Dr. Saver reported ties to Medtronic, Stryker, Cognition Medical, Covidien, Neuravi, BrainsGate, Pfizer, Bristol-Myers Squibb, Boehringer Ingelheim, ZZ Biotech, St. Jude Medical, and Genentech. His associates reported ties to numerous industry sources.

BOSTON – A medication management strategy to minimize the effect of drug-drug interactions (DDIs) between warfarin and common antimicrobials resulted in significantly greater time within therapeutic range for anticoagulation, as well as a numerically smaller, but nonsignificant, number of bleeding events.

After implementation of a comprehensive inpatient and postdischarge guideline to manage DDIs between warfarin and 16 antibiotics, antivirals, or antifungal medications, patients’ in-hospital time within therapeutic range (TWTR) increased to 72% from 50% preimplementation (P = .043). Warfarin TWTR also improved across care transitions after the guidelines were implemented, rising to 70% from 46% (P = .012). No bleeding events occurred in the group studied after the guidelines were instituted, compared with four events in the comparator preguidelines group (P = .11).

Nghi Ha, PharmD, MPH, and his collaborators sought to determine whether formalizing a process to manage potentially dangerous antimicrobial-warfarin DDIs made a difference in achieving more TWTR for patients, as determined by international normalized ratio (INR) values. Dr. Ha, a clinical pharmacist at University of Michigan Health System, Ann Arbor, presented the results during a poster session at the annual meeting of the American Society for Microbiology.

Secondary outcome measures studied by Dr. Ha and his associates included the incidence of thrombosis or major bleeding events, as well as tracking documentation of medications and the anticoagulation plan in progress and discharge notes.

Patients were included if they were at least 18 years old, and if they were on 3 days or more of an antimicrobial with potential for DDI with warfarin. Patients who were also newly on other medications with the potential for significant DDI with warfarin were excluded to minimize the potential for confounding.

Dr. Ha and his collaborators characterized the study as a retrospective, single-center, quasi-experimental design of a pharmacist-run anticoagulation service. The study examined endpoints before and after implementation of comprehensive guidelines, and included 78 preguideline and 31 postguideline patients.

The guidelines drafted by the investigators and tested in their study included empiric adjustment of warfarin dosing for patients who were placed on an antibiotic with high potential to increase INR. These included many azoles and sulfamethoxazole/trimethoprim, for which initial warfarin doses were empirically reduced 20%-30% for patients whose INRs were therapeutic at the start of antimicrobial therapy. For ciprofloxacin, erythromycin, clarithromycin, and isoniazid, the guidelines recommended initial empiric warfarin dose reductions of 10%-15%.

Patients whose INRs were subtherapeutic at the beginning of therapy and who received these antimicrobials were continued on their maintenance warfarin dosing, but were monitored for rising INRs over the first 48 hours, for consideration of dosing adjustment as needed. Individuals with supratherapeutic INRs at the beginning of antimicrobial dosing had their warfarin doses reduced or held by a more aggressive algorithm based on their initial INR, and based on the potential of the antimicrobial to increase INR.

On discharge, patients were either reverted to their previous warfarin regimen if they had been stable on that regimen, or had their inpatient warfarin dosing increased by 10%-20%.

Drugs that were deemed to have moderate potential to increase INR included doxycycline, levofloxacin, moxifloxacin, quinupristin/dalfopristin, telaprevir, boceprevir, and simeprevir. For these medications, the protocol recommended no initial dose adjustment, but recommended monitoring of INR to consider a dose reduction if needed. On hospital discharge, patients who had been on these medications were to resume their previous warfarin dosing.

Antimicrobials with potential to decrease INR included nafcillin, for which the protocol recommended empiric warfarin dose increases of 25%-50%, starting 3-5 days after nafcillin was begun. Patients on rifampin or rifabutin were to increase their warfarin by 20%-30%, also 3-5 days after beginning the antibiotics. Patients on ritonavir alone, or any protease inhibitor given for HIV along with ritonavir, were closely monitored, but no empiric dosing adjustments were made.

Patients with initial subtherapeutic INRs had dosing increased by 30%-50% for nafcillin and 20%-30% for rifampin and rifabutin. A stepped algorithm for dose adjustment or withholding was also developed for these medications to treat patients with initial supratherapeutic INRs. Patients on these medications were to resume their previous warfarin dosing, with monitoring and adjustment if they had not been previously stable.

Documentation of antimicrobial-warfarin DDI in the anticoagulation service discharge summary improved significantly once the guidelines were implemented (40% compared with 14%, P = .02). There was not a significant improvement in DDI documentation in daily progress notes.

The comprehensive intervention included the formulation of guidelines and requirements to document the medication interaction in the medical chart. Other interventions included training for clinical pharmacists and the development of pocket cards and flyers to educate team members about the new guidelines. The electronic health record had triggers built and implemented to prompt consideration of warfarin/antimicrobial DDIs as well.

Dr. Ha and his coauthors noted that the uncontrolled nature of the pre-post study design was one limitation of the study. Also, the real-world design of the study meant that investigators could not control for diet, comorbidities, and other factors that have the potential to affect INR. “Implementing a process to identify high-risk antimicrobial-warfarin DDIs and provide guidelines for empiric warfarin dose adjustment … can improve INR time within therapeutic range,” noted Dr. Ha and his coauthors.

The study authors reported no external sources of funding and no conflicts of interest.

koakes@frontlinemedcom.com

On Twitter @karioakes

BOSTON – A medication management strategy to minimize the effect of drug-drug interactions (DDIs) between warfarin and common antimicrobials resulted in significantly greater time within therapeutic range for anticoagulation, as well as a numerically smaller, but nonsignificant, number of bleeding events.

After implementation of a comprehensive inpatient and postdischarge guideline to manage DDIs between warfarin and 16 antibiotics, antivirals, or antifungal medications, patients’ in-hospital time within therapeutic range (TWTR) increased to 72% from 50% preimplementation (P = .043). Warfarin TWTR also improved across care transitions after the guidelines were implemented, rising to 70% from 46% (P = .012). No bleeding events occurred in the group studied after the guidelines were instituted, compared with four events in the comparator preguidelines group (P = .11).

Nghi Ha, PharmD, MPH, and his collaborators sought to determine whether formalizing a process to manage potentially dangerous antimicrobial-warfarin DDIs made a difference in achieving more TWTR for patients, as determined by international normalized ratio (INR) values. Dr. Ha, a clinical pharmacist at University of Michigan Health System, Ann Arbor, presented the results during a poster session at the annual meeting of the American Society for Microbiology.

Secondary outcome measures studied by Dr. Ha and his associates included the incidence of thrombosis or major bleeding events, as well as tracking documentation of medications and the anticoagulation plan in progress and discharge notes.

Patients were included if they were at least 18 years old, and if they were on 3 days or more of an antimicrobial with potential for DDI with warfarin. Patients who were also newly on other medications with the potential for significant DDI with warfarin were excluded to minimize the potential for confounding.

Dr. Ha and his collaborators characterized the study as a retrospective, single-center, quasi-experimental design of a pharmacist-run anticoagulation service. The study examined endpoints before and after implementation of comprehensive guidelines, and included 78 preguideline and 31 postguideline patients.

The guidelines drafted by the investigators and tested in their study included empiric adjustment of warfarin dosing for patients who were placed on an antibiotic with high potential to increase INR. These included many azoles and sulfamethoxazole/trimethoprim, for which initial warfarin doses were empirically reduced 20%-30% for patients whose INRs were therapeutic at the start of antimicrobial therapy. For ciprofloxacin, erythromycin, clarithromycin, and isoniazid, the guidelines recommended initial empiric warfarin dose reductions of 10%-15%.

Patients whose INRs were subtherapeutic at the beginning of therapy and who received these antimicrobials were continued on their maintenance warfarin dosing, but were monitored for rising INRs over the first 48 hours, for consideration of dosing adjustment as needed. Individuals with supratherapeutic INRs at the beginning of antimicrobial dosing had their warfarin doses reduced or held by a more aggressive algorithm based on their initial INR, and based on the potential of the antimicrobial to increase INR.

On discharge, patients were either reverted to their previous warfarin regimen if they had been stable on that regimen, or had their inpatient warfarin dosing increased by 10%-20%.

Drugs that were deemed to have moderate potential to increase INR included doxycycline, levofloxacin, moxifloxacin, quinupristin/dalfopristin, telaprevir, boceprevir, and simeprevir. For these medications, the protocol recommended no initial dose adjustment, but recommended monitoring of INR to consider a dose reduction if needed. On hospital discharge, patients who had been on these medications were to resume their previous warfarin dosing.

Antimicrobials with potential to decrease INR included nafcillin, for which the protocol recommended empiric warfarin dose increases of 25%-50%, starting 3-5 days after nafcillin was begun. Patients on rifampin or rifabutin were to increase their warfarin by 20%-30%, also 3-5 days after beginning the antibiotics. Patients on ritonavir alone, or any protease inhibitor given for HIV along with ritonavir, were closely monitored, but no empiric dosing adjustments were made.

Patients with initial subtherapeutic INRs had dosing increased by 30%-50% for nafcillin and 20%-30% for rifampin and rifabutin. A stepped algorithm for dose adjustment or withholding was also developed for these medications to treat patients with initial supratherapeutic INRs. Patients on these medications were to resume their previous warfarin dosing, with monitoring and adjustment if they had not been previously stable.

Documentation of antimicrobial-warfarin DDI in the anticoagulation service discharge summary improved significantly once the guidelines were implemented (40% compared with 14%, P = .02). There was not a significant improvement in DDI documentation in daily progress notes.

The comprehensive intervention included the formulation of guidelines and requirements to document the medication interaction in the medical chart. Other interventions included training for clinical pharmacists and the development of pocket cards and flyers to educate team members about the new guidelines. The electronic health record had triggers built and implemented to prompt consideration of warfarin/antimicrobial DDIs as well.

Dr. Ha and his coauthors noted that the uncontrolled nature of the pre-post study design was one limitation of the study. Also, the real-world design of the study meant that investigators could not control for diet, comorbidities, and other factors that have the potential to affect INR. “Implementing a process to identify high-risk antimicrobial-warfarin DDIs and provide guidelines for empiric warfarin dose adjustment … can improve INR time within therapeutic range,” noted Dr. Ha and his coauthors.

The study authors reported no external sources of funding and no conflicts of interest.

koakes@frontlinemedcom.com

On Twitter @karioakes

BOSTON – A medication management strategy to minimize the effect of drug-drug interactions (DDIs) between warfarin and common antimicrobials resulted in significantly greater time within therapeutic range for anticoagulation, as well as a numerically smaller, but nonsignificant, number of bleeding events.

After implementation of a comprehensive inpatient and postdischarge guideline to manage DDIs between warfarin and 16 antibiotics, antivirals, or antifungal medications, patients’ in-hospital time within therapeutic range (TWTR) increased to 72% from 50% preimplementation (P = .043). Warfarin TWTR also improved across care transitions after the guidelines were implemented, rising to 70% from 46% (P = .012). No bleeding events occurred in the group studied after the guidelines were instituted, compared with four events in the comparator preguidelines group (P = .11).

Nghi Ha, PharmD, MPH, and his collaborators sought to determine whether formalizing a process to manage potentially dangerous antimicrobial-warfarin DDIs made a difference in achieving more TWTR for patients, as determined by international normalized ratio (INR) values. Dr. Ha, a clinical pharmacist at University of Michigan Health System, Ann Arbor, presented the results during a poster session at the annual meeting of the American Society for Microbiology.

Secondary outcome measures studied by Dr. Ha and his associates included the incidence of thrombosis or major bleeding events, as well as tracking documentation of medications and the anticoagulation plan in progress and discharge notes.

Patients were included if they were at least 18 years old, and if they were on 3 days or more of an antimicrobial with potential for DDI with warfarin. Patients who were also newly on other medications with the potential for significant DDI with warfarin were excluded to minimize the potential for confounding.

Dr. Ha and his collaborators characterized the study as a retrospective, single-center, quasi-experimental design of a pharmacist-run anticoagulation service. The study examined endpoints before and after implementation of comprehensive guidelines, and included 78 preguideline and 31 postguideline patients.

The guidelines drafted by the investigators and tested in their study included empiric adjustment of warfarin dosing for patients who were placed on an antibiotic with high potential to increase INR. These included many azoles and sulfamethoxazole/trimethoprim, for which initial warfarin doses were empirically reduced 20%-30% for patients whose INRs were therapeutic at the start of antimicrobial therapy. For ciprofloxacin, erythromycin, clarithromycin, and isoniazid, the guidelines recommended initial empiric warfarin dose reductions of 10%-15%.

Patients whose INRs were subtherapeutic at the beginning of therapy and who received these antimicrobials were continued on their maintenance warfarin dosing, but were monitored for rising INRs over the first 48 hours, for consideration of dosing adjustment as needed. Individuals with supratherapeutic INRs at the beginning of antimicrobial dosing had their warfarin doses reduced or held by a more aggressive algorithm based on their initial INR, and based on the potential of the antimicrobial to increase INR.

On discharge, patients were either reverted to their previous warfarin regimen if they had been stable on that regimen, or had their inpatient warfarin dosing increased by 10%-20%.

Drugs that were deemed to have moderate potential to increase INR included doxycycline, levofloxacin, moxifloxacin, quinupristin/dalfopristin, telaprevir, boceprevir, and simeprevir. For these medications, the protocol recommended no initial dose adjustment, but recommended monitoring of INR to consider a dose reduction if needed. On hospital discharge, patients who had been on these medications were to resume their previous warfarin dosing.

Antimicrobials with potential to decrease INR included nafcillin, for which the protocol recommended empiric warfarin dose increases of 25%-50%, starting 3-5 days after nafcillin was begun. Patients on rifampin or rifabutin were to increase their warfarin by 20%-30%, also 3-5 days after beginning the antibiotics. Patients on ritonavir alone, or any protease inhibitor given for HIV along with ritonavir, were closely monitored, but no empiric dosing adjustments were made.

Patients with initial subtherapeutic INRs had dosing increased by 30%-50% for nafcillin and 20%-30% for rifampin and rifabutin. A stepped algorithm for dose adjustment or withholding was also developed for these medications to treat patients with initial supratherapeutic INRs. Patients on these medications were to resume their previous warfarin dosing, with monitoring and adjustment if they had not been previously stable.

Documentation of antimicrobial-warfarin DDI in the anticoagulation service discharge summary improved significantly once the guidelines were implemented (40% compared with 14%, P = .02). There was not a significant improvement in DDI documentation in daily progress notes.

The comprehensive intervention included the formulation of guidelines and requirements to document the medication interaction in the medical chart. Other interventions included training for clinical pharmacists and the development of pocket cards and flyers to educate team members about the new guidelines. The electronic health record had triggers built and implemented to prompt consideration of warfarin/antimicrobial DDIs as well.

Dr. Ha and his coauthors noted that the uncontrolled nature of the pre-post study design was one limitation of the study. Also, the real-world design of the study meant that investigators could not control for diet, comorbidities, and other factors that have the potential to affect INR. “Implementing a process to identify high-risk antimicrobial-warfarin DDIs and provide guidelines for empiric warfarin dose adjustment … can improve INR time within therapeutic range,” noted Dr. Ha and his coauthors.

The study authors reported no external sources of funding and no conflicts of interest.

koakes@frontlinemedcom.com

On Twitter @karioakes

The NOAC revolution has happened.

New oral anticoagulants (NOACs) now claim the majority of the oral anticoagulant market in patients with new atrial fibrillation, wresting the advantage from warfarin in the U.S. and globally. This is the promise NOACs held even while still in development, the potential to whittle warfarin use down to a shadow of what it was. Despite a sputtering reception when the first NOAC, dabigatran (Pradaxa), came onto the U.S. market in late 2010, the four NOACs (also apixaban [Eliquis], edoxaban [Savaysa], and rivaroxaban [Xarelto]) now available in the United States and elsewhere gradually gained traction and today they collectively form the most widely used oral anticoagulant option for patients newly diagnosed with atrial fibrillation.

Mitchel L. Zoler/Frontline Medical News

Data reported in August at the annual congress of the European Society of Cardiology showed that in Denmark during the first half of 2015, NOACs accounted for 73% of oral anticoagulant prescriptions for patients with newly diagnosed atrial fibrillation, Kasper Gadsboll, MD, reported. He and his associates studied NOAC and warfarin use in a total of 108,410 atrial fibrillation patients newly diagnosed starting in 2005. Through 2010, warfarin was the only option, but starting in early 2011 when the first NOAC became available in Denmark, use of the class rose sharply with a corresponding plummet in warfarin prescriptions. Not only did the NOACs largely supplant warfarin during 2011-2015, but they also powered an overall rise in the percentage of atrial fibrillation patients treated with an oral anticoagulant, boosting the rate by a relative 75% between the end of 2009 and mid-2015.

“People were reluctant to start an oral anticoagulant because they feared bleeding. Now with NOACs they are not as fearful,” said Dr. Gadsboll, a cardiology researcher at Gentofte Hospital in Hellerup, Denmark. He also noted that in Denmark the national health system pays for prescribed drugs, so the increased direct cost for NOAC treatment in place of warfarin is covered by the Danish government.

“NOAC uptake is gathering steam,” commented Stuart J. Connolly, MD, an electrophysiologist and professor of medicine at McMaster University in Hamilton, Ontario. “When the government pays for it, people prescribe it more, but increased NOAC use is happening everywhere,” said Dr. Connolly, who led major trials that assessed dabigatran and apixaban in atrial fibrillation patients. “I’ve seen Canadian data that show warfarin use is falling and NOAC use is increasing. People are more willing to prescribe NOACs because they are safer,” he said in an interview.

The most current U.S. data I found came from the IMS Health National Disease and Therapeutic Index in 2014, based on a survey of a representative sample of about 4,800 U.S. office-based physicians. The results showed that the NOAC share of oral anticoagulant use in patients who had office visits for atrial fibrillation jumped from 6% of patients in early 2011 to roughly half of all atrial fibrillation patients, 48%, during 2014 (Am J Med. 2015 Dec;128[12]:1300-5). That trajectory makes it likely that by now NOACs have a clear lead.

It’s a similar story in several European countries, such as in Belgium where NOACs now account for about 70% of new prescriptions for atrial fibrillation patients, commented Freek W.A. Verheugt, MD. In the Netherlands, however, NOACs have not taken off, in large part because a popular and entrenched thrombosis clinic system exists that employs thousands of Dutch workers, thereby making choice of an anticoagulant drug a social and political question as well as a medical one, he said. “Warfarin is still indicated for patients with an artificial heart valve or poor kidney function,” noted Dr. Verheugt, professor of cardiology at the University of Nijmegen in the Netherlands, “but a majority of atrial fibrillation patients will eventually change to a NOAC. Even when treatment with warfarin has a good time-in-therapeutic-range, NOACs are still better. They are so much safer.”

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

The NOAC revolution has happened.

New oral anticoagulants (NOACs) now claim the majority of the oral anticoagulant market in patients with new atrial fibrillation, wresting the advantage from warfarin in the U.S. and globally. This is the promise NOACs held even while still in development, the potential to whittle warfarin use down to a shadow of what it was. Despite a sputtering reception when the first NOAC, dabigatran (Pradaxa), came onto the U.S. market in late 2010, the four NOACs (also apixaban [Eliquis], edoxaban [Savaysa], and rivaroxaban [Xarelto]) now available in the United States and elsewhere gradually gained traction and today they collectively form the most widely used oral anticoagulant option for patients newly diagnosed with atrial fibrillation.

Mitchel L. Zoler/Frontline Medical News

Data reported in August at the annual congress of the European Society of Cardiology showed that in Denmark during the first half of 2015, NOACs accounted for 73% of oral anticoagulant prescriptions for patients with newly diagnosed atrial fibrillation, Kasper Gadsboll, MD, reported. He and his associates studied NOAC and warfarin use in a total of 108,410 atrial fibrillation patients newly diagnosed starting in 2005. Through 2010, warfarin was the only option, but starting in early 2011 when the first NOAC became available in Denmark, use of the class rose sharply with a corresponding plummet in warfarin prescriptions. Not only did the NOACs largely supplant warfarin during 2011-2015, but they also powered an overall rise in the percentage of atrial fibrillation patients treated with an oral anticoagulant, boosting the rate by a relative 75% between the end of 2009 and mid-2015.

“People were reluctant to start an oral anticoagulant because they feared bleeding. Now with NOACs they are not as fearful,” said Dr. Gadsboll, a cardiology researcher at Gentofte Hospital in Hellerup, Denmark. He also noted that in Denmark the national health system pays for prescribed drugs, so the increased direct cost for NOAC treatment in place of warfarin is covered by the Danish government.

“NOAC uptake is gathering steam,” commented Stuart J. Connolly, MD, an electrophysiologist and professor of medicine at McMaster University in Hamilton, Ontario. “When the government pays for it, people prescribe it more, but increased NOAC use is happening everywhere,” said Dr. Connolly, who led major trials that assessed dabigatran and apixaban in atrial fibrillation patients. “I’ve seen Canadian data that show warfarin use is falling and NOAC use is increasing. People are more willing to prescribe NOACs because they are safer,” he said in an interview.

The most current U.S. data I found came from the IMS Health National Disease and Therapeutic Index in 2014, based on a survey of a representative sample of about 4,800 U.S. office-based physicians. The results showed that the NOAC share of oral anticoagulant use in patients who had office visits for atrial fibrillation jumped from 6% of patients in early 2011 to roughly half of all atrial fibrillation patients, 48%, during 2014 (Am J Med. 2015 Dec;128[12]:1300-5). That trajectory makes it likely that by now NOACs have a clear lead.

It’s a similar story in several European countries, such as in Belgium where NOACs now account for about 70% of new prescriptions for atrial fibrillation patients, commented Freek W.A. Verheugt, MD. In the Netherlands, however, NOACs have not taken off, in large part because a popular and entrenched thrombosis clinic system exists that employs thousands of Dutch workers, thereby making choice of an anticoagulant drug a social and political question as well as a medical one, he said. “Warfarin is still indicated for patients with an artificial heart valve or poor kidney function,” noted Dr. Verheugt, professor of cardiology at the University of Nijmegen in the Netherlands, “but a majority of atrial fibrillation patients will eventually change to a NOAC. Even when treatment with warfarin has a good time-in-therapeutic-range, NOACs are still better. They are so much safer.”

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

The NOAC revolution has happened.

New oral anticoagulants (NOACs) now claim the majority of the oral anticoagulant market in patients with new atrial fibrillation, wresting the advantage from warfarin in the U.S. and globally. This is the promise NOACs held even while still in development, the potential to whittle warfarin use down to a shadow of what it was. Despite a sputtering reception when the first NOAC, dabigatran (Pradaxa), came onto the U.S. market in late 2010, the four NOACs (also apixaban [Eliquis], edoxaban [Savaysa], and rivaroxaban [Xarelto]) now available in the United States and elsewhere gradually gained traction and today they collectively form the most widely used oral anticoagulant option for patients newly diagnosed with atrial fibrillation.

Mitchel L. Zoler/Frontline Medical News

Data reported in August at the annual congress of the European Society of Cardiology showed that in Denmark during the first half of 2015, NOACs accounted for 73% of oral anticoagulant prescriptions for patients with newly diagnosed atrial fibrillation, Kasper Gadsboll, MD, reported. He and his associates studied NOAC and warfarin use in a total of 108,410 atrial fibrillation patients newly diagnosed starting in 2005. Through 2010, warfarin was the only option, but starting in early 2011 when the first NOAC became available in Denmark, use of the class rose sharply with a corresponding plummet in warfarin prescriptions. Not only did the NOACs largely supplant warfarin during 2011-2015, but they also powered an overall rise in the percentage of atrial fibrillation patients treated with an oral anticoagulant, boosting the rate by a relative 75% between the end of 2009 and mid-2015.

“People were reluctant to start an oral anticoagulant because they feared bleeding. Now with NOACs they are not as fearful,” said Dr. Gadsboll, a cardiology researcher at Gentofte Hospital in Hellerup, Denmark. He also noted that in Denmark the national health system pays for prescribed drugs, so the increased direct cost for NOAC treatment in place of warfarin is covered by the Danish government.

“NOAC uptake is gathering steam,” commented Stuart J. Connolly, MD, an electrophysiologist and professor of medicine at McMaster University in Hamilton, Ontario. “When the government pays for it, people prescribe it more, but increased NOAC use is happening everywhere,” said Dr. Connolly, who led major trials that assessed dabigatran and apixaban in atrial fibrillation patients. “I’ve seen Canadian data that show warfarin use is falling and NOAC use is increasing. People are more willing to prescribe NOACs because they are safer,” he said in an interview.

The most current U.S. data I found came from the IMS Health National Disease and Therapeutic Index in 2014, based on a survey of a representative sample of about 4,800 U.S. office-based physicians. The results showed that the NOAC share of oral anticoagulant use in patients who had office visits for atrial fibrillation jumped from 6% of patients in early 2011 to roughly half of all atrial fibrillation patients, 48%, during 2014 (Am J Med. 2015 Dec;128[12]:1300-5). That trajectory makes it likely that by now NOACs have a clear lead.

It’s a similar story in several European countries, such as in Belgium where NOACs now account for about 70% of new prescriptions for atrial fibrillation patients, commented Freek W.A. Verheugt, MD. In the Netherlands, however, NOACs have not taken off, in large part because a popular and entrenched thrombosis clinic system exists that employs thousands of Dutch workers, thereby making choice of an anticoagulant drug a social and political question as well as a medical one, he said. “Warfarin is still indicated for patients with an artificial heart valve or poor kidney function,” noted Dr. Verheugt, professor of cardiology at the University of Nijmegen in the Netherlands, “but a majority of atrial fibrillation patients will eventually change to a NOAC. Even when treatment with warfarin has a good time-in-therapeutic-range, NOACs are still better. They are so much safer.”

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

Higher levels of free thyroxine are associated with an increased risk of sudden cardiac death, even in euthyroid adults, according to a report published online Sept. 6 in Circulation.

Thyroid dysfunction, even in the subclinical range, is known to correlate with increased cardiovascular disease, but until now a possible link between free thyroxine levels and sudden cardiac death (SCD) has never been explored in the general population. Any factors that could improve prediction of SCD in the general population would be helpful because almost half of these cases are the first indication that the patient had heart disease, said Layal Chaker, MD, of the Rotterdam Thyroid Center and the departments of internal medicine and epidemiology, Erasmus University, Rotterdam, and her associates.

©jarun011/Thinkstock.com

They assessed SCD among 10,318 participants in the Rotterdam Study, a prospective population-based cohort study examining endocrine, cardiovascular, neurologic, ophthalmologic, and psychiatric diseases in middle-aged and older adults in the Netherlands. Men and women aged 45-106 years who had thyroid testing at baseline were followed for a median of 9.2 years (range, 4-21 years) for the development of SCD. There were 261 cases of SCD, and 231 of these occurred in euthyroid participants.

Higher levels of free thyroxine (T4) were associated with an increased risk of SCD, with a hazard ratio of 1.87 for every 1 ng/dL increase in free T4. When the analysis was confined to the 231 euthyroid participants, this association was even stronger, with an HR of 2.26, the investigators said (Circulation 2016 Sept 6. doi: 10.1161/CirculationAHA.115.020789).

The findings were similar in several sensitivity analyses, including one that excluded participants who had an unwitnessed SCD. In addition, adjustment of the data to account for the presence or absence of diabetes, as well as exclusion of patients who had heart failure, did not alter the risk estimates significantly. The results also were consistent across all age groups and both sexes, Dr. Chaker and her associates said.

The exact mechanism for the association between free thyroxine and SCD is not yet known but appears to be independent of traditional cardiovascular risk factors. “Bigger sample size and more detailed data are needed to determine whether these associations share the same or have distinct pathways,” they added.

The Netherlands Organisation for Health Research and Development and Erasmus Medical Center supported the study. Dr. Chaker and her associates reported having no relevant financial disclosures.

Higher levels of free thyroxine are associated with an increased risk of sudden cardiac death, even in euthyroid adults, according to a report published online Sept. 6 in Circulation.

Thyroid dysfunction, even in the subclinical range, is known to correlate with increased cardiovascular disease, but until now a possible link between free thyroxine levels and sudden cardiac death (SCD) has never been explored in the general population. Any factors that could improve prediction of SCD in the general population would be helpful because almost half of these cases are the first indication that the patient had heart disease, said Layal Chaker, MD, of the Rotterdam Thyroid Center and the departments of internal medicine and epidemiology, Erasmus University, Rotterdam, and her associates.

©jarun011/Thinkstock.com

They assessed SCD among 10,318 participants in the Rotterdam Study, a prospective population-based cohort study examining endocrine, cardiovascular, neurologic, ophthalmologic, and psychiatric diseases in middle-aged and older adults in the Netherlands. Men and women aged 45-106 years who had thyroid testing at baseline were followed for a median of 9.2 years (range, 4-21 years) for the development of SCD. There were 261 cases of SCD, and 231 of these occurred in euthyroid participants.

Higher levels of free thyroxine (T4) were associated with an increased risk of SCD, with a hazard ratio of 1.87 for every 1 ng/dL increase in free T4. When the analysis was confined to the 231 euthyroid participants, this association was even stronger, with an HR of 2.26, the investigators said (Circulation 2016 Sept 6. doi: 10.1161/CirculationAHA.115.020789).

The findings were similar in several sensitivity analyses, including one that excluded participants who had an unwitnessed SCD. In addition, adjustment of the data to account for the presence or absence of diabetes, as well as exclusion of patients who had heart failure, did not alter the risk estimates significantly. The results also were consistent across all age groups and both sexes, Dr. Chaker and her associates said.

The exact mechanism for the association between free thyroxine and SCD is not yet known but appears to be independent of traditional cardiovascular risk factors. “Bigger sample size and more detailed data are needed to determine whether these associations share the same or have distinct pathways,” they added.

The Netherlands Organisation for Health Research and Development and Erasmus Medical Center supported the study. Dr. Chaker and her associates reported having no relevant financial disclosures.

Higher levels of free thyroxine are associated with an increased risk of sudden cardiac death, even in euthyroid adults, according to a report published online Sept. 6 in Circulation.

Thyroid dysfunction, even in the subclinical range, is known to correlate with increased cardiovascular disease, but until now a possible link between free thyroxine levels and sudden cardiac death (SCD) has never been explored in the general population. Any factors that could improve prediction of SCD in the general population would be helpful because almost half of these cases are the first indication that the patient had heart disease, said Layal Chaker, MD, of the Rotterdam Thyroid Center and the departments of internal medicine and epidemiology, Erasmus University, Rotterdam, and her associates.

©jarun011/Thinkstock.com

They assessed SCD among 10,318 participants in the Rotterdam Study, a prospective population-based cohort study examining endocrine, cardiovascular, neurologic, ophthalmologic, and psychiatric diseases in middle-aged and older adults in the Netherlands. Men and women aged 45-106 years who had thyroid testing at baseline were followed for a median of 9.2 years (range, 4-21 years) for the development of SCD. There were 261 cases of SCD, and 231 of these occurred in euthyroid participants.

Higher levels of free thyroxine (T4) were associated with an increased risk of SCD, with a hazard ratio of 1.87 for every 1 ng/dL increase in free T4. When the analysis was confined to the 231 euthyroid participants, this association was even stronger, with an HR of 2.26, the investigators said (Circulation 2016 Sept 6. doi: 10.1161/CirculationAHA.115.020789).

The findings were similar in several sensitivity analyses, including one that excluded participants who had an unwitnessed SCD. In addition, adjustment of the data to account for the presence or absence of diabetes, as well as exclusion of patients who had heart failure, did not alter the risk estimates significantly. The results also were consistent across all age groups and both sexes, Dr. Chaker and her associates said.

The exact mechanism for the association between free thyroxine and SCD is not yet known but appears to be independent of traditional cardiovascular risk factors. “Bigger sample size and more detailed data are needed to determine whether these associations share the same or have distinct pathways,” they added.

The Netherlands Organisation for Health Research and Development and Erasmus Medical Center supported the study. Dr. Chaker and her associates reported having no relevant financial disclosures.

Two Trevo clot retrieval devices can now be marketed as an initial therapy to reduce paralysis from strokes that are caused by blood clots, according to a press release from the Food and Drug Administration.

Previously, the only first-line treatment approved for acute ischemic stroke was tissue plasminogen activator (TPA) delivered intravenously. The FDA approved Trevo devices based on a clinical trial in which 29% of patients treated with the Trevo device combined with TPA and medical management of blood pressure and disability symptoms were shown to be functionally independent 3 months after their stroke, compared with only 19% of patients treated with TPA plus medical management alone.

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

The Trevo devices are approved for usage within 6 hours of symptom onset and only following treatment with TPA, which should be administered within 3 hours of stroke onset. Associated risks with Trevo device usage include failure to retrieve the blood clot, device malfunctions including breakage and navigation difficulties, potential damage of blood vessels, and the chance of perforation or hemorrhage.

The Trevo device was first approved by the FDA in 2012 to remove blood clots in order to restore blood flow in stroke patients who could not receive TPA or for those patients who did not respond to TPA therapy. The current approval expands the devices’ indication to a broader group of patients, according to the release.

“This is the first time FDA has allowed the use of these devices alongside TPA, which has the potential to help further reduce the devastating disabilities associated with strokes compared to the use of TPA alone. Now health care providers and their patients have another tool for treating stroke and potentially preventing long-term disability,” Carlos Peña, PhD, director of the division of neurological and physical medicine devices at the FDA’s Center for Devices and Radiological Health, said in the press release.

Find the full press release on the FDA website.

lfranki@frontlinemedcom.com

Two Trevo clot retrieval devices can now be marketed as an initial therapy to reduce paralysis from strokes that are caused by blood clots, according to a press release from the Food and Drug Administration.

Previously, the only first-line treatment approved for acute ischemic stroke was tissue plasminogen activator (TPA) delivered intravenously. The FDA approved Trevo devices based on a clinical trial in which 29% of patients treated with the Trevo device combined with TPA and medical management of blood pressure and disability symptoms were shown to be functionally independent 3 months after their stroke, compared with only 19% of patients treated with TPA plus medical management alone.

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

The Trevo devices are approved for usage within 6 hours of symptom onset and only following treatment with TPA, which should be administered within 3 hours of stroke onset. Associated risks with Trevo device usage include failure to retrieve the blood clot, device malfunctions including breakage and navigation difficulties, potential damage of blood vessels, and the chance of perforation or hemorrhage.

The Trevo device was first approved by the FDA in 2012 to remove blood clots in order to restore blood flow in stroke patients who could not receive TPA or for those patients who did not respond to TPA therapy. The current approval expands the devices’ indication to a broader group of patients, according to the release.

“This is the first time FDA has allowed the use of these devices alongside TPA, which has the potential to help further reduce the devastating disabilities associated with strokes compared to the use of TPA alone. Now health care providers and their patients have another tool for treating stroke and potentially preventing long-term disability,” Carlos Peña, PhD, director of the division of neurological and physical medicine devices at the FDA’s Center for Devices and Radiological Health, said in the press release.

Find the full press release on the FDA website.

lfranki@frontlinemedcom.com

Two Trevo clot retrieval devices can now be marketed as an initial therapy to reduce paralysis from strokes that are caused by blood clots, according to a press release from the Food and Drug Administration.

Previously, the only first-line treatment approved for acute ischemic stroke was tissue plasminogen activator (TPA) delivered intravenously. The FDA approved Trevo devices based on a clinical trial in which 29% of patients treated with the Trevo device combined with TPA and medical management of blood pressure and disability symptoms were shown to be functionally independent 3 months after their stroke, compared with only 19% of patients treated with TPA plus medical management alone.

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

The Trevo devices are approved for usage within 6 hours of symptom onset and only following treatment with TPA, which should be administered within 3 hours of stroke onset. Associated risks with Trevo device usage include failure to retrieve the blood clot, device malfunctions including breakage and navigation difficulties, potential damage of blood vessels, and the chance of perforation or hemorrhage.

The Trevo device was first approved by the FDA in 2012 to remove blood clots in order to restore blood flow in stroke patients who could not receive TPA or for those patients who did not respond to TPA therapy. The current approval expands the devices’ indication to a broader group of patients, according to the release.

“This is the first time FDA has allowed the use of these devices alongside TPA, which has the potential to help further reduce the devastating disabilities associated with strokes compared to the use of TPA alone. Now health care providers and their patients have another tool for treating stroke and potentially preventing long-term disability,” Carlos Peña, PhD, director of the division of neurological and physical medicine devices at the FDA’s Center for Devices and Radiological Health, said in the press release.

Find the full press release on the FDA website.

lfranki@frontlinemedcom.com

ROME – Results of the largest-ever randomized clinical trial of anticoagulation for electrical cardioversion of patients with nonvalvular atrial fibrillation demonstrate that edoxaban is a safe, effective, and convenient alternative to the standard strategy of enoxaparin as a bridge to warfarin.

The ENSURE-AF trial was a phase IIIb study involving 2,199 patients with atrial fibrillation who underwent electrical cardioversion at 239 sites in the United States and 19 European countries. The key finding: The edoxaban-treated group had rates of thromboembolism and major bleeding at 28-30 days follow-up similar to those of the enoxaparin/warfarin-treated controls.

And edoxaban offered a major practical advantage: Because “edoxaban kicks in within 2 hours, you can do the procedure just 2 hours after initiation of therapy in a patient with a reassuring transesophageal echocardiographic exam, which is definitely not possible with warfarin,” Andreas Goette, MD, observed at the annual congress of the European Society of Cardiology.

Bruce Jancin/Frontline Medical News

Roughly half of participants were treated at centers that don’t routinely use a transesophageal echo-guided management strategy and therefore delayed cardioversion until patients were anticoagulated for at least 3 weeks. The safety and efficacy outcomes were similar regardless of whether or not transesophageal echocardiography (TEE) guidance was used, according to Dr. Goette of St. Vincenz Hospital in Paderborn, Germany.

Edoxaban (Savaysa) was prescribed at 60 mg once daily except in patients weighing 60 kg or less or having a creatinine clearance rate of 15-50 mL/min, in which case they received 30 mg once daily. In the control arm, enoxaparin (Lovenox) was used until warfarin achieved an International Normalized Ratio of 2.0-3.0. Patients in the enoxaparin/warfarin arm spent a mean of 71% of their treatment time within the target INR range.

The primary efficacy outcome was the 28-day composite of stroke or other systemic embolic events, MI, or cardiovascular mortality. The rate was 0.5% in the edoxaban arm and 1.0% in the enoxaparin/warfarin group. In patients whose management strategy was TEE-guided, the rate was 0.3% in the edoxaban group and 0.8% with enoxaparin/warfarin. In non-TEE-guided patients, the rates were 0.6% and 1.2% with edoxaban and warfarin, respectively.

Although rates were consistently numerically lower in the edoxaban group, the differences did not reach statistical significance, Dr. Goette explained.

The combined rate of major or clinically relevant nonmajor bleeding through 30 days was 1.5% with edoxaban and similar at 1.0% with enoxaparin plus warfarin. Three patients in the edoxaban group experienced a major bleeding event, as did five in the comparator arm.

Because anticoagulation with edoxaban is so convenient and allows cardioversion to safely be performed in short order, the ENSURE-AF investigators are in the process of calculating the potential savings in health care costs obtainable through this strategy, the cardiologist said.

ENSURE-AF provides the first prospective randomized data on the use of edoxaban as an alternative to warfarin for pericardioversion anticoagulation. There has been one other randomized trial of a novel oral anticoagulant (NOAC) in this setting, the 1,504-patient X-VeRT trial (Eur Heart J. 2014 Dec 14;35[47]:3346-55), involving rivaroxaban (Xarelto).

Riccardo Cappato, MD, first author of the X-VeRT publication, served as the designated discussant for ENSURE-AF. He noted that the results of the two trials are “completely superimposable.” Rates of the composite efficacy endpoint were identical at 0.5% for both NOACs versus 1.0% for the vitamin K antagonist arms of X-VeRT and ENSURE-AF. The major bleeding rates also were identical for edoxaban and rivaroxaban in the two studies. Moreover, the major bleeding rates associated with warfarin or other vitamin K antagonists were spot-on the same in the two trials.

Bruce Jancin/Frontline Medical News

“It’s a rather unusual situation for such large numbers of patients,” observed Dr. Cappato of Humanitas Research Institute in Milan.

“These data go very clearly in the same direction. I think a good take-home message here for us today is that both of these novel oral anticoagulants can be safely and efficaciously applied to patients undergoing elective cardioversion of nonvalvular atrial fibrillation,” he added.

In an interview, Mark A. Creager, MD, immediate past president of the American Heart Association, said that many U.S. physicians are switching to NOACs for this purpose.

“We are already using the novel oral anticoagulants to facilitate anticoagulation for patients undergoing cardioversion, so ENSURE-AF provides objective evidence that edoxaban is a reasonable drug,” said Dr. Creager, director of the Dartmouth-Hitchcock Heart and Vascular Center in New Hampshire.

The ENSURE-AF trial was funded by Daiichi Sankyo. Dr. Goette and Dr. Cappato reported receiving research grants from and serving as consultants to that company and other pharmaceutical and medical device manufacturers.

Simultaneously with Dr. Goette’s presentation in Rome, the ENSURE-AF results were published online Aug. 30 in The Lancet.

bjancin@frontlinemedcom.com

ROME – Results of the largest-ever randomized clinical trial of anticoagulation for electrical cardioversion of patients with nonvalvular atrial fibrillation demonstrate that edoxaban is a safe, effective, and convenient alternative to the standard strategy of enoxaparin as a bridge to warfarin.

The ENSURE-AF trial was a phase IIIb study involving 2,199 patients with atrial fibrillation who underwent electrical cardioversion at 239 sites in the United States and 19 European countries. The key finding: The edoxaban-treated group had rates of thromboembolism and major bleeding at 28-30 days follow-up similar to those of the enoxaparin/warfarin-treated controls.

And edoxaban offered a major practical advantage: Because “edoxaban kicks in within 2 hours, you can do the procedure just 2 hours after initiation of therapy in a patient with a reassuring transesophageal echocardiographic exam, which is definitely not possible with warfarin,” Andreas Goette, MD, observed at the annual congress of the European Society of Cardiology.

Bruce Jancin/Frontline Medical News

Roughly half of participants were treated at centers that don’t routinely use a transesophageal echo-guided management strategy and therefore delayed cardioversion until patients were anticoagulated for at least 3 weeks. The safety and efficacy outcomes were similar regardless of whether or not transesophageal echocardiography (TEE) guidance was used, according to Dr. Goette of St. Vincenz Hospital in Paderborn, Germany.

Edoxaban (Savaysa) was prescribed at 60 mg once daily except in patients weighing 60 kg or less or having a creatinine clearance rate of 15-50 mL/min, in which case they received 30 mg once daily. In the control arm, enoxaparin (Lovenox) was used until warfarin achieved an International Normalized Ratio of 2.0-3.0. Patients in the enoxaparin/warfarin arm spent a mean of 71% of their treatment time within the target INR range.

The primary efficacy outcome was the 28-day composite of stroke or other systemic embolic events, MI, or cardiovascular mortality. The rate was 0.5% in the edoxaban arm and 1.0% in the enoxaparin/warfarin group. In patients whose management strategy was TEE-guided, the rate was 0.3% in the edoxaban group and 0.8% with enoxaparin/warfarin. In non-TEE-guided patients, the rates were 0.6% and 1.2% with edoxaban and warfarin, respectively.

Although rates were consistently numerically lower in the edoxaban group, the differences did not reach statistical significance, Dr. Goette explained.

The combined rate of major or clinically relevant nonmajor bleeding through 30 days was 1.5% with edoxaban and similar at 1.0% with enoxaparin plus warfarin. Three patients in the edoxaban group experienced a major bleeding event, as did five in the comparator arm.

Because anticoagulation with edoxaban is so convenient and allows cardioversion to safely be performed in short order, the ENSURE-AF investigators are in the process of calculating the potential savings in health care costs obtainable through this strategy, the cardiologist said.

ENSURE-AF provides the first prospective randomized data on the use of edoxaban as an alternative to warfarin for pericardioversion anticoagulation. There has been one other randomized trial of a novel oral anticoagulant (NOAC) in this setting, the 1,504-patient X-VeRT trial (Eur Heart J. 2014 Dec 14;35[47]:3346-55), involving rivaroxaban (Xarelto).

Riccardo Cappato, MD, first author of the X-VeRT publication, served as the designated discussant for ENSURE-AF. He noted that the results of the two trials are “completely superimposable.” Rates of the composite efficacy endpoint were identical at 0.5% for both NOACs versus 1.0% for the vitamin K antagonist arms of X-VeRT and ENSURE-AF. The major bleeding rates also were identical for edoxaban and rivaroxaban in the two studies. Moreover, the major bleeding rates associated with warfarin or other vitamin K antagonists were spot-on the same in the two trials.

Bruce Jancin/Frontline Medical News

“It’s a rather unusual situation for such large numbers of patients,” observed Dr. Cappato of Humanitas Research Institute in Milan.

“These data go very clearly in the same direction. I think a good take-home message here for us today is that both of these novel oral anticoagulants can be safely and efficaciously applied to patients undergoing elective cardioversion of nonvalvular atrial fibrillation,” he added.

In an interview, Mark A. Creager, MD, immediate past president of the American Heart Association, said that many U.S. physicians are switching to NOACs for this purpose.

“We are already using the novel oral anticoagulants to facilitate anticoagulation for patients undergoing cardioversion, so ENSURE-AF provides objective evidence that edoxaban is a reasonable drug,” said Dr. Creager, director of the Dartmouth-Hitchcock Heart and Vascular Center in New Hampshire.

The ENSURE-AF trial was funded by Daiichi Sankyo. Dr. Goette and Dr. Cappato reported receiving research grants from and serving as consultants to that company and other pharmaceutical and medical device manufacturers.

Simultaneously with Dr. Goette’s presentation in Rome, the ENSURE-AF results were published online Aug. 30 in The Lancet.

bjancin@frontlinemedcom.com

ROME – Results of the largest-ever randomized clinical trial of anticoagulation for electrical cardioversion of patients with nonvalvular atrial fibrillation demonstrate that edoxaban is a safe, effective, and convenient alternative to the standard strategy of enoxaparin as a bridge to warfarin.

The ENSURE-AF trial was a phase IIIb study involving 2,199 patients with atrial fibrillation who underwent electrical cardioversion at 239 sites in the United States and 19 European countries. The key finding: The edoxaban-treated group had rates of thromboembolism and major bleeding at 28-30 days follow-up similar to those of the enoxaparin/warfarin-treated controls.

And edoxaban offered a major practical advantage: Because “edoxaban kicks in within 2 hours, you can do the procedure just 2 hours after initiation of therapy in a patient with a reassuring transesophageal echocardiographic exam, which is definitely not possible with warfarin,” Andreas Goette, MD, observed at the annual congress of the European Society of Cardiology.

Bruce Jancin/Frontline Medical News

Roughly half of participants were treated at centers that don’t routinely use a transesophageal echo-guided management strategy and therefore delayed cardioversion until patients were anticoagulated for at least 3 weeks. The safety and efficacy outcomes were similar regardless of whether or not transesophageal echocardiography (TEE) guidance was used, according to Dr. Goette of St. Vincenz Hospital in Paderborn, Germany.

Edoxaban (Savaysa) was prescribed at 60 mg once daily except in patients weighing 60 kg or less or having a creatinine clearance rate of 15-50 mL/min, in which case they received 30 mg once daily. In the control arm, enoxaparin (Lovenox) was used until warfarin achieved an International Normalized Ratio of 2.0-3.0. Patients in the enoxaparin/warfarin arm spent a mean of 71% of their treatment time within the target INR range.

The primary efficacy outcome was the 28-day composite of stroke or other systemic embolic events, MI, or cardiovascular mortality. The rate was 0.5% in the edoxaban arm and 1.0% in the enoxaparin/warfarin group. In patients whose management strategy was TEE-guided, the rate was 0.3% in the edoxaban group and 0.8% with enoxaparin/warfarin. In non-TEE-guided patients, the rates were 0.6% and 1.2% with edoxaban and warfarin, respectively.

Although rates were consistently numerically lower in the edoxaban group, the differences did not reach statistical significance, Dr. Goette explained.

The combined rate of major or clinically relevant nonmajor bleeding through 30 days was 1.5% with edoxaban and similar at 1.0% with enoxaparin plus warfarin. Three patients in the edoxaban group experienced a major bleeding event, as did five in the comparator arm.

Because anticoagulation with edoxaban is so convenient and allows cardioversion to safely be performed in short order, the ENSURE-AF investigators are in the process of calculating the potential savings in health care costs obtainable through this strategy, the cardiologist said.

ENSURE-AF provides the first prospective randomized data on the use of edoxaban as an alternative to warfarin for pericardioversion anticoagulation. There has been one other randomized trial of a novel oral anticoagulant (NOAC) in this setting, the 1,504-patient X-VeRT trial (Eur Heart J. 2014 Dec 14;35[47]:3346-55), involving rivaroxaban (Xarelto).

Riccardo Cappato, MD, first author of the X-VeRT publication, served as the designated discussant for ENSURE-AF. He noted that the results of the two trials are “completely superimposable.” Rates of the composite efficacy endpoint were identical at 0.5% for both NOACs versus 1.0% for the vitamin K antagonist arms of X-VeRT and ENSURE-AF. The major bleeding rates also were identical for edoxaban and rivaroxaban in the two studies. Moreover, the major bleeding rates associated with warfarin or other vitamin K antagonists were spot-on the same in the two trials.

Bruce Jancin/Frontline Medical News

“It’s a rather unusual situation for such large numbers of patients,” observed Dr. Cappato of Humanitas Research Institute in Milan.

“These data go very clearly in the same direction. I think a good take-home message here for us today is that both of these novel oral anticoagulants can be safely and efficaciously applied to patients undergoing elective cardioversion of nonvalvular atrial fibrillation,” he added.

In an interview, Mark A. Creager, MD, immediate past president of the American Heart Association, said that many U.S. physicians are switching to NOACs for this purpose.

“We are already using the novel oral anticoagulants to facilitate anticoagulation for patients undergoing cardioversion, so ENSURE-AF provides objective evidence that edoxaban is a reasonable drug,” said Dr. Creager, director of the Dartmouth-Hitchcock Heart and Vascular Center in New Hampshire.

The ENSURE-AF trial was funded by Daiichi Sankyo. Dr. Goette and Dr. Cappato reported receiving research grants from and serving as consultants to that company and other pharmaceutical and medical device manufacturers.

Simultaneously with Dr. Goette’s presentation in Rome, the ENSURE-AF results were published online Aug. 30 in The Lancet.

bjancin@frontlinemedcom.com

ROME – Combined exposure to low LDL cholesterol and systolic blood pressure is associated with multiplicative and cumulative effects over time, Brian A. Ference, MD, said in a video interview at the annual congress of the European Society of Cardiology.

Indeed, long-term exposure to a combined 1-mmol/L lower LDL cholesterol and 10-mm Hg lower systolic BP was associated with up to a 90% lower risk of major cardiovascular events in the “naturally randomized” study he presented. The investigators used the 102,000 participants’ genetic LDL and BP scores in a Mendelian design.

If these lower LDL and blood pressure levels are sustained over decades, “those cumulative effects multiply, resulting in potentially dramatic reductions in the lifetime risk of cardiovascular events from even modestly lower levels of LDL and systolic blood pressure,” Dr. Ference of Wayne State University, Detroit, told reporter Bruce Jancin.

chackett@frontlinemedcom.com

ROME – Combined exposure to low LDL cholesterol and systolic blood pressure is associated with multiplicative and cumulative effects over time, Brian A. Ference, MD, said in a video interview at the annual congress of the European Society of Cardiology.

Indeed, long-term exposure to a combined 1-mmol/L lower LDL cholesterol and 10-mm Hg lower systolic BP was associated with up to a 90% lower risk of major cardiovascular events in the “naturally randomized” study he presented. The investigators used the 102,000 participants’ genetic LDL and BP scores in a Mendelian design.

If these lower LDL and blood pressure levels are sustained over decades, “those cumulative effects multiply, resulting in potentially dramatic reductions in the lifetime risk of cardiovascular events from even modestly lower levels of LDL and systolic blood pressure,” Dr. Ference of Wayne State University, Detroit, told reporter Bruce Jancin.

chackett@frontlinemedcom.com

ROME – Combined exposure to low LDL cholesterol and systolic blood pressure is associated with multiplicative and cumulative effects over time, Brian A. Ference, MD, said in a video interview at the annual congress of the European Society of Cardiology.

Indeed, long-term exposure to a combined 1-mmol/L lower LDL cholesterol and 10-mm Hg lower systolic BP was associated with up to a 90% lower risk of major cardiovascular events in the “naturally randomized” study he presented. The investigators used the 102,000 participants’ genetic LDL and BP scores in a Mendelian design.

If these lower LDL and blood pressure levels are sustained over decades, “those cumulative effects multiply, resulting in potentially dramatic reductions in the lifetime risk of cardiovascular events from even modestly lower levels of LDL and systolic blood pressure,” Dr. Ference of Wayne State University, Detroit, told reporter Bruce Jancin.

chackett@frontlinemedcom.com