Cardiology

Habitual coffee drinking was not associated with a heightened risk of cardiac arrhythmias in a study of more than 300,000 people.

In fact, an adjusted analysis found that “each additional cup of coffee intake was associated with a 3% lower risk of incident arrhythmia,” Eun-jeong Kim, MD, of the division of cardiology at the University of California, San Francisco, and colleagues reported in JAMA Internal Medicine.

In addition, genetic differences that affect caffeine metabolism did not significantly influence the odds of arrhythmias, the researchers found.

Still, these findings should not necessarily encourage people to start drinking coffee if they don’t already, or to guzzle additional cups with abandon, they said.

American Heart Association

“We certainly don’t want to say drink coffee and it will reduce your risk of arrhythmias,” study author Gregory M. Marcus, MD, MAS, associate chief of cardiology for research at UCSF Health, said in an interview. “But rather, we think the main point is that a blanket prohibition against coffee or caffeine to reduce the risk of arrhythmias among patients who have a diagnosis of arrhythmias is likely unwarranted. And given some evidence that coffee consumption may actually have other benefits regarding diabetes, mood, and perhaps overall mortality, it may be problematic to admonish patients to avoid coffee or caffeine when it is not really warranted.”
 

Methods and results

The conventional wisdom that caffeine increases arrhythmic risk has not been well substantiated. To further examine whether moderate, habitual coffee drinking relates to arrhythmia risk, and whether certain genetic variants influence the association, Dr. Kim and colleagues analyzed data from the UK Biobank. They focused on longitudinal data collected between 2006 and 2018 from 386,258 people who did not have a prior diagnosis of arrhythmia.

Participants had an average age of 56 years, and about 52% were female. They provided information about their coffee consumption, and the researchers grouped the participants into eight categories based on their daily coffee intake: 0, less than 1, 1, 2, 3, 4, 5, and 6 or more cups per day.

Over an average follow-up of 4.5 years, 16,979 participants developed an incident arrhythmia. After adjusting for demographic characteristics, comorbid conditions, and lifestyle habits, the decreased risk with each cup of coffee was similar for atrial fibrillation or flutter (hazard ratio, 0.97) and supraventricular tachycardia (HR, 0.96).

Taking into account genetic variations that relate to caffeine metabolism did not modify the findings. Mendelian randomization analyses that used a polygenic score of inherited caffeine metabolism patterns “failed to provide evidence that caffeine consumption leads to a greater risk of arrhythmias,” the researchers said.

Professional society guidelines have suggested staying away from caffeinated products to reduce the risk of arrhythmia, but this guidance has “relied on assumed mechanisms and a small observational study from 1980,” the authors wrote. Subsequent research has indicated that coffee’s reputation of increasing the risk of arrhythmia may be undeserved.

“The investigators should be commended on performing a high-quality observational study to try to further understand the association between coffee consumption and arrhythmias, or the lack of one,” commented Zachary D. Goldberger, MD, MS, with the division of cardiovascular medicine at the University of Wisconsin–Madison, who was not involved in the study. “This is not a randomized, controlled trial, and coffee consumption was self-reported, but the methods employed are rigorous, despite these and other important limitations. However, we need to be extremely cautious in how we interpret these findings, and not use these data as a prescription for more coffee. It’s important to recognize that this study is not telling us to drink more coffee, or start drinking coffee, to protect against developing arrhythmias. However, it should offer more reassurance that moderate coffee consumption is not necessarily harmful, and will not always lead to arrhythmias. This is important, given the widespread notion that coffee is universally proarrhythmic.”
 

A call for personalized guidance

“As the investigators note, there are definitely biologically plausible reasons how coffee and caffeine may not cause arrhythmias, and may be possibly protective in some, despite being a stimulant,” Dr. Goldberger said. “However, if your patient is reporting palpitations or symptoms of an arrhythmia, and feels they be related to coffee or caffeine, we should not use this study to tell them that coffee may not be the culprit. We need to listen to our patients, and the decision to reduce coffee consumption to reduce these symptoms needs to be personalized.”

The effect size was small, and only about 4% of the participants developed an arrhythmia, Dr. Goldberger and Rodney A. Hayward, MD, wrote in an invited commentary on the study in JAMA Internal Medicine. Dr. Hayward is a professor of public health and internal medicine at the University of Michigan, Ann Arbor, and a senior investigator at the Ann Arbor Veterans Affairs Center for Clinical Management Research.

“Unfortunately, coffee consumption was self-reported at a single time point. Not only can this lead to recall bias, but subsequent and substantial changes in coffee consumption are also possible, including reductions due to new signs or symptoms,” they said.
 

No evidence that coffee ups risk for developing arrhythmias

Another recent study suggests that people may alter their coffee consumption depending on their baseline cardiovascular health, according to the commentary.

Overall, the results “strengthen the evidence that caffeine is not proarrhythmic, but they should not be taken as proving that coffee is an antiarrhythmic—this distinction is of paramount importance,” Dr. Goldberger and Dr. Hayward wrote. “Health care professionals can reassure patients that there is no evidence that drinking coffee increases the risk for developing arrhythmias. This is particularly important for the many patients with benign palpitations who are devastated when they think, or are told, that they have to stop drinking coffee. Given current evidence, this is entirely a patient-preference decision, not a medical one.”

Dr. Marcus, a cardiac electrophysiologist, sees patients with arrhythmias all the time. They tend to “come in fairly convinced that caffeine is to be avoided when they have arrhythmias,” he said. “Often, they been told by their primary care physician or their general cardiologist to avoid caffeine because they have an arrhythmia.

“What I suggest to my patients is that they feel free to go ahead and experiment and try coffee,” Dr. Marcus said.

Still, Dr. Marcus suspects that there are some individuals in whom caffeine is a trigger for the arrhythmia. But evidence indicates these cases likely are rare, and avoiding caffeine need not apply to the general population, particularly “given the potential health benefits of benefits of coffee and also, frankly, just the enhanced quality of life that people can enjoy drinking a good cup of coffee.”

The research was conducted using the UK Biobank resource, which was established by the Wellcome Trust, the Medical Research Council, the U.K. Department of Health, and the Scottish government. The UK Biobank has received funding from other agencies and foundations as well. Dr. Marcus disclosed grants from Baylis, Medtronic, and Eight Sleep outside the submitted work. In addition, he reported consulting for Johnson & Johnson and InCarda, and holding equity in InCarda. A coauthor received salary support from the National Institutes of Health during the study. Dr. Goldberger and Dr. Hayward disclosed no conflicts of interest.

jremaly@mdedge.com

Habitual coffee drinking was not associated with a heightened risk of cardiac arrhythmias in a study of more than 300,000 people.

In fact, an adjusted analysis found that “each additional cup of coffee intake was associated with a 3% lower risk of incident arrhythmia,” Eun-jeong Kim, MD, of the division of cardiology at the University of California, San Francisco, and colleagues reported in JAMA Internal Medicine.

In addition, genetic differences that affect caffeine metabolism did not significantly influence the odds of arrhythmias, the researchers found.

Still, these findings should not necessarily encourage people to start drinking coffee if they don’t already, or to guzzle additional cups with abandon, they said.

American Heart Association

“We certainly don’t want to say drink coffee and it will reduce your risk of arrhythmias,” study author Gregory M. Marcus, MD, MAS, associate chief of cardiology for research at UCSF Health, said in an interview. “But rather, we think the main point is that a blanket prohibition against coffee or caffeine to reduce the risk of arrhythmias among patients who have a diagnosis of arrhythmias is likely unwarranted. And given some evidence that coffee consumption may actually have other benefits regarding diabetes, mood, and perhaps overall mortality, it may be problematic to admonish patients to avoid coffee or caffeine when it is not really warranted.”
 

Methods and results

The conventional wisdom that caffeine increases arrhythmic risk has not been well substantiated. To further examine whether moderate, habitual coffee drinking relates to arrhythmia risk, and whether certain genetic variants influence the association, Dr. Kim and colleagues analyzed data from the UK Biobank. They focused on longitudinal data collected between 2006 and 2018 from 386,258 people who did not have a prior diagnosis of arrhythmia.

Participants had an average age of 56 years, and about 52% were female. They provided information about their coffee consumption, and the researchers grouped the participants into eight categories based on their daily coffee intake: 0, less than 1, 1, 2, 3, 4, 5, and 6 or more cups per day.

Over an average follow-up of 4.5 years, 16,979 participants developed an incident arrhythmia. After adjusting for demographic characteristics, comorbid conditions, and lifestyle habits, the decreased risk with each cup of coffee was similar for atrial fibrillation or flutter (hazard ratio, 0.97) and supraventricular tachycardia (HR, 0.96).

Taking into account genetic variations that relate to caffeine metabolism did not modify the findings. Mendelian randomization analyses that used a polygenic score of inherited caffeine metabolism patterns “failed to provide evidence that caffeine consumption leads to a greater risk of arrhythmias,” the researchers said.

Professional society guidelines have suggested staying away from caffeinated products to reduce the risk of arrhythmia, but this guidance has “relied on assumed mechanisms and a small observational study from 1980,” the authors wrote. Subsequent research has indicated that coffee’s reputation of increasing the risk of arrhythmia may be undeserved.

“The investigators should be commended on performing a high-quality observational study to try to further understand the association between coffee consumption and arrhythmias, or the lack of one,” commented Zachary D. Goldberger, MD, MS, with the division of cardiovascular medicine at the University of Wisconsin–Madison, who was not involved in the study. “This is not a randomized, controlled trial, and coffee consumption was self-reported, but the methods employed are rigorous, despite these and other important limitations. However, we need to be extremely cautious in how we interpret these findings, and not use these data as a prescription for more coffee. It’s important to recognize that this study is not telling us to drink more coffee, or start drinking coffee, to protect against developing arrhythmias. However, it should offer more reassurance that moderate coffee consumption is not necessarily harmful, and will not always lead to arrhythmias. This is important, given the widespread notion that coffee is universally proarrhythmic.”
 

A call for personalized guidance

“As the investigators note, there are definitely biologically plausible reasons how coffee and caffeine may not cause arrhythmias, and may be possibly protective in some, despite being a stimulant,” Dr. Goldberger said. “However, if your patient is reporting palpitations or symptoms of an arrhythmia, and feels they be related to coffee or caffeine, we should not use this study to tell them that coffee may not be the culprit. We need to listen to our patients, and the decision to reduce coffee consumption to reduce these symptoms needs to be personalized.”

The effect size was small, and only about 4% of the participants developed an arrhythmia, Dr. Goldberger and Rodney A. Hayward, MD, wrote in an invited commentary on the study in JAMA Internal Medicine. Dr. Hayward is a professor of public health and internal medicine at the University of Michigan, Ann Arbor, and a senior investigator at the Ann Arbor Veterans Affairs Center for Clinical Management Research.

“Unfortunately, coffee consumption was self-reported at a single time point. Not only can this lead to recall bias, but subsequent and substantial changes in coffee consumption are also possible, including reductions due to new signs or symptoms,” they said.
 

No evidence that coffee ups risk for developing arrhythmias

Another recent study suggests that people may alter their coffee consumption depending on their baseline cardiovascular health, according to the commentary.

Overall, the results “strengthen the evidence that caffeine is not proarrhythmic, but they should not be taken as proving that coffee is an antiarrhythmic—this distinction is of paramount importance,” Dr. Goldberger and Dr. Hayward wrote. “Health care professionals can reassure patients that there is no evidence that drinking coffee increases the risk for developing arrhythmias. This is particularly important for the many patients with benign palpitations who are devastated when they think, or are told, that they have to stop drinking coffee. Given current evidence, this is entirely a patient-preference decision, not a medical one.”

Dr. Marcus, a cardiac electrophysiologist, sees patients with arrhythmias all the time. They tend to “come in fairly convinced that caffeine is to be avoided when they have arrhythmias,” he said. “Often, they been told by their primary care physician or their general cardiologist to avoid caffeine because they have an arrhythmia.

“What I suggest to my patients is that they feel free to go ahead and experiment and try coffee,” Dr. Marcus said.

Still, Dr. Marcus suspects that there are some individuals in whom caffeine is a trigger for the arrhythmia. But evidence indicates these cases likely are rare, and avoiding caffeine need not apply to the general population, particularly “given the potential health benefits of benefits of coffee and also, frankly, just the enhanced quality of life that people can enjoy drinking a good cup of coffee.”

The research was conducted using the UK Biobank resource, which was established by the Wellcome Trust, the Medical Research Council, the U.K. Department of Health, and the Scottish government. The UK Biobank has received funding from other agencies and foundations as well. Dr. Marcus disclosed grants from Baylis, Medtronic, and Eight Sleep outside the submitted work. In addition, he reported consulting for Johnson & Johnson and InCarda, and holding equity in InCarda. A coauthor received salary support from the National Institutes of Health during the study. Dr. Goldberger and Dr. Hayward disclosed no conflicts of interest.

jremaly@mdedge.com

Habitual coffee drinking was not associated with a heightened risk of cardiac arrhythmias in a study of more than 300,000 people.

In fact, an adjusted analysis found that “each additional cup of coffee intake was associated with a 3% lower risk of incident arrhythmia,” Eun-jeong Kim, MD, of the division of cardiology at the University of California, San Francisco, and colleagues reported in JAMA Internal Medicine.

In addition, genetic differences that affect caffeine metabolism did not significantly influence the odds of arrhythmias, the researchers found.

Still, these findings should not necessarily encourage people to start drinking coffee if they don’t already, or to guzzle additional cups with abandon, they said.

American Heart Association

“We certainly don’t want to say drink coffee and it will reduce your risk of arrhythmias,” study author Gregory M. Marcus, MD, MAS, associate chief of cardiology for research at UCSF Health, said in an interview. “But rather, we think the main point is that a blanket prohibition against coffee or caffeine to reduce the risk of arrhythmias among patients who have a diagnosis of arrhythmias is likely unwarranted. And given some evidence that coffee consumption may actually have other benefits regarding diabetes, mood, and perhaps overall mortality, it may be problematic to admonish patients to avoid coffee or caffeine when it is not really warranted.”
 

Methods and results

The conventional wisdom that caffeine increases arrhythmic risk has not been well substantiated. To further examine whether moderate, habitual coffee drinking relates to arrhythmia risk, and whether certain genetic variants influence the association, Dr. Kim and colleagues analyzed data from the UK Biobank. They focused on longitudinal data collected between 2006 and 2018 from 386,258 people who did not have a prior diagnosis of arrhythmia.

Participants had an average age of 56 years, and about 52% were female. They provided information about their coffee consumption, and the researchers grouped the participants into eight categories based on their daily coffee intake: 0, less than 1, 1, 2, 3, 4, 5, and 6 or more cups per day.

Over an average follow-up of 4.5 years, 16,979 participants developed an incident arrhythmia. After adjusting for demographic characteristics, comorbid conditions, and lifestyle habits, the decreased risk with each cup of coffee was similar for atrial fibrillation or flutter (hazard ratio, 0.97) and supraventricular tachycardia (HR, 0.96).

Taking into account genetic variations that relate to caffeine metabolism did not modify the findings. Mendelian randomization analyses that used a polygenic score of inherited caffeine metabolism patterns “failed to provide evidence that caffeine consumption leads to a greater risk of arrhythmias,” the researchers said.

Professional society guidelines have suggested staying away from caffeinated products to reduce the risk of arrhythmia, but this guidance has “relied on assumed mechanisms and a small observational study from 1980,” the authors wrote. Subsequent research has indicated that coffee’s reputation of increasing the risk of arrhythmia may be undeserved.

“The investigators should be commended on performing a high-quality observational study to try to further understand the association between coffee consumption and arrhythmias, or the lack of one,” commented Zachary D. Goldberger, MD, MS, with the division of cardiovascular medicine at the University of Wisconsin–Madison, who was not involved in the study. “This is not a randomized, controlled trial, and coffee consumption was self-reported, but the methods employed are rigorous, despite these and other important limitations. However, we need to be extremely cautious in how we interpret these findings, and not use these data as a prescription for more coffee. It’s important to recognize that this study is not telling us to drink more coffee, or start drinking coffee, to protect against developing arrhythmias. However, it should offer more reassurance that moderate coffee consumption is not necessarily harmful, and will not always lead to arrhythmias. This is important, given the widespread notion that coffee is universally proarrhythmic.”
 

A call for personalized guidance

“As the investigators note, there are definitely biologically plausible reasons how coffee and caffeine may not cause arrhythmias, and may be possibly protective in some, despite being a stimulant,” Dr. Goldberger said. “However, if your patient is reporting palpitations or symptoms of an arrhythmia, and feels they be related to coffee or caffeine, we should not use this study to tell them that coffee may not be the culprit. We need to listen to our patients, and the decision to reduce coffee consumption to reduce these symptoms needs to be personalized.”

The effect size was small, and only about 4% of the participants developed an arrhythmia, Dr. Goldberger and Rodney A. Hayward, MD, wrote in an invited commentary on the study in JAMA Internal Medicine. Dr. Hayward is a professor of public health and internal medicine at the University of Michigan, Ann Arbor, and a senior investigator at the Ann Arbor Veterans Affairs Center for Clinical Management Research.

“Unfortunately, coffee consumption was self-reported at a single time point. Not only can this lead to recall bias, but subsequent and substantial changes in coffee consumption are also possible, including reductions due to new signs or symptoms,” they said.
 

No evidence that coffee ups risk for developing arrhythmias

Another recent study suggests that people may alter their coffee consumption depending on their baseline cardiovascular health, according to the commentary.

Overall, the results “strengthen the evidence that caffeine is not proarrhythmic, but they should not be taken as proving that coffee is an antiarrhythmic—this distinction is of paramount importance,” Dr. Goldberger and Dr. Hayward wrote. “Health care professionals can reassure patients that there is no evidence that drinking coffee increases the risk for developing arrhythmias. This is particularly important for the many patients with benign palpitations who are devastated when they think, or are told, that they have to stop drinking coffee. Given current evidence, this is entirely a patient-preference decision, not a medical one.”

Dr. Marcus, a cardiac electrophysiologist, sees patients with arrhythmias all the time. They tend to “come in fairly convinced that caffeine is to be avoided when they have arrhythmias,” he said. “Often, they been told by their primary care physician or their general cardiologist to avoid caffeine because they have an arrhythmia.

“What I suggest to my patients is that they feel free to go ahead and experiment and try coffee,” Dr. Marcus said.

Still, Dr. Marcus suspects that there are some individuals in whom caffeine is a trigger for the arrhythmia. But evidence indicates these cases likely are rare, and avoiding caffeine need not apply to the general population, particularly “given the potential health benefits of benefits of coffee and also, frankly, just the enhanced quality of life that people can enjoy drinking a good cup of coffee.”

The research was conducted using the UK Biobank resource, which was established by the Wellcome Trust, the Medical Research Council, the U.K. Department of Health, and the Scottish government. The UK Biobank has received funding from other agencies and foundations as well. Dr. Marcus disclosed grants from Baylis, Medtronic, and Eight Sleep outside the submitted work. In addition, he reported consulting for Johnson & Johnson and InCarda, and holding equity in InCarda. A coauthor received salary support from the National Institutes of Health during the study. Dr. Goldberger and Dr. Hayward disclosed no conflicts of interest.

jremaly@mdedge.com

Following a transcatheter aortic valve replacement (TAVR), direct oral anticoagulants (DOACs) are preferable to vitamin K antagonists (VKAs) in patients who are candidates for oral anticoagulants, according to data drawn from a large multicenter French TAVR registry.

When oral anticoagulation is appropriate following TAVR, such as in patients with atrial fibrillation, “DOACs are associated with improved survival and lower incidence of bleeding, compared to VKA,” reported a team of investigators led by Martine Gilard, MD, PhD, director of interventional cardiology, Brest (France) University Hospital Center.

The comparison, using propensity score matching, is not definitive, but it might be the best data currently available to support DOACs over VKA until a randomized trial is completed, according to Dr. Gilard, senior author of the newly published study.

Asked in an interview if DOACs should now be used preferentially after TAVR when patients are indicated for oral anticoagulation, Dr. Gilard replied, “My answer is yes.”

Of more than 24,000 TAVR patients in the French TAVI and FRANCE2 multicenter registries, which are linked to the French single-payer claims database (SNDS), 8,962 (36.4%) received an oral anticoagulant following their procedure. Of these, 2,180 (24.3%) received a DOAC and the remaining received VKA.

By linking data from the registries to the SNDS, outcomes were tracked. Propensity matching was employed to control for differences in baseline characteristics, including age, body mass index, functional class, diabetes, comorbidities, and past medical history.

On the primary endpoint of mortality at the end of 3 years, the rates were 35.6% and 31.2% for VKA and DOACs, respectively. This translated in a 37% greater hazard ratio for death among those treated with VKA (P < .005).

The rate of major bleeding, a secondary endpoint, was also higher (12.3% vs. 8.4%) and significantly different (HR, 1.65; P < .005) for VKA versus DOACs. The rates of ischemic stroke, acute coronary syndrome, and hemorrhagic stroke were all numerically higher in patients treated with VKA than DOACs, although none of these differences reached statistical significance.
 

Residual confounding cannot be discounted

“The large number of events allowed for taking into account a higher number of potential confounders with appropriate statistical power,” according to the authors. However, they acknowledged that residual confounding cannot be eliminated by propensity matching and conceded that prospective data are needed for a definitive comparison.

In an accompanying editorial, Daniele Giacoppo, MD, a cardiologist at Alto Vicentino Hospital, Santorso, Italy, enlarged on this point . In addition to the inherent limitations of retrospective data, he also noted that data from other studies addressing the same question have been inconsistent.

Of these studies, he pointed to the ATLANTIS trial, presented 2 months ago at the annual meeting of the American College of Cardiology. This study failed to show an advantage for the DOAC apixaban over VKA in TAVR patients for the primary composite outcome of time to death, myocardial infarction, systemic emboli, valve thrombosis, or major bleeding. Although this study was not limited to patients with an indication for oral anticoagulants, Dr. Giacoppo pointed out that there was no advantage, even among the subgroup of patients who did have an indication.
 

Data are supportive in absence of trial results

In general, Dr. Giacoppo agreed that the French registry are generally supportive of DOACs over VKA in TAVR patients with an indication for oral anticoagulation, but he cautioned that blanket statements are difficult. He anticipates better information from a randomized trial called ENVISAGE-TAVI AF, which is comparing edoxaban with VKA following TAVR in atrial fibrillation patients who have an indication for oral anticoagulation, but he indicated that some individualization of choice will be needed among those high or low relative risks of thrombotic events or bleeding.

“The concerns related to DOACs after TAVR are most confined to patients without an indication for oral anticoagulation,” Dr. Giacoppo said in an interview. In patients with an indication, “oral anticoagulation alone without antithrombotic therapy significantly reduced the risk of bleeding” in several studies, he added, citing in particular the POPular TAVI trial.

Issues about when to employ – or not employ – both oral anticoagulation and antithrombotic therapy based on such factors as bleeding risk remain unresolved, but “in aggregate, waiting for additional high-quality data, the use of a DOAC in patients with an indication for oral anticoagulation who underwent TAVR seems to be safe,” Dr. Giacoppo said. He thinks that the “higher predictability of DOACS compared to vitamin K antagonists might translate into lower bleeding rates over time in a real-world, unselected population.”
 

Benefit-to-risk ratio requires attention

A similar concern about balancing risks and benefits of oral anticoagulation in TAVR patients with an indication for oral anticoagulation was emphasized by Ron Waksman, MD, associate director, division of cardiology, MedStar Washington (D.C.) Hospital Center.

“The TAVR population is elderly in general and so are at high risk for bleeding with any additional anticoagulation,” Dr. Waksman said. He cited data that bring into question the utility of using a DOAC in TAVR patients without an additional indication for anticoagulation, but he believes DOACs do make sense in those who were on and had an indication for a DOAC even before TAVR.

Patients who had atrial fibrillation or another indication “should continue to take the DOAC after TAVR. This population can be assumed to have less bleeding risk as they are vetted as safe for DOACs before their TAVR procedure,” he said.

Although mortality was the primary endpoint of the French registry evaluation, it is the bleeding risk that is a dominant concern, according to Romain Didier, MD, PhD, the first author of this study who performed this work in collaboration with Dr. Gilard.

“We really believe that VKA use in real life after TAVR, even with INR monitoring, is associated with a higher risk of bleeding as compared to DOACs,” he said. It is for this reason that “we currently use DOACs as a first choice in patients who require anticoagulant after TAVR.”

Dr. Gilard, Dr. Didier, and Dr. Giacoppo reported no potential conflicts of interest. Dr. Waksman reported financial relationships with Amgen, AstraZeneca, Boston Scientific, Cardioset, Cardiovascular Systems, Chiesi, MedAlliance, Medtronic, and Pi-Cardia.

Following a transcatheter aortic valve replacement (TAVR), direct oral anticoagulants (DOACs) are preferable to vitamin K antagonists (VKAs) in patients who are candidates for oral anticoagulants, according to data drawn from a large multicenter French TAVR registry.

When oral anticoagulation is appropriate following TAVR, such as in patients with atrial fibrillation, “DOACs are associated with improved survival and lower incidence of bleeding, compared to VKA,” reported a team of investigators led by Martine Gilard, MD, PhD, director of interventional cardiology, Brest (France) University Hospital Center.

The comparison, using propensity score matching, is not definitive, but it might be the best data currently available to support DOACs over VKA until a randomized trial is completed, according to Dr. Gilard, senior author of the newly published study.

Asked in an interview if DOACs should now be used preferentially after TAVR when patients are indicated for oral anticoagulation, Dr. Gilard replied, “My answer is yes.”

Of more than 24,000 TAVR patients in the French TAVI and FRANCE2 multicenter registries, which are linked to the French single-payer claims database (SNDS), 8,962 (36.4%) received an oral anticoagulant following their procedure. Of these, 2,180 (24.3%) received a DOAC and the remaining received VKA.

By linking data from the registries to the SNDS, outcomes were tracked. Propensity matching was employed to control for differences in baseline characteristics, including age, body mass index, functional class, diabetes, comorbidities, and past medical history.

On the primary endpoint of mortality at the end of 3 years, the rates were 35.6% and 31.2% for VKA and DOACs, respectively. This translated in a 37% greater hazard ratio for death among those treated with VKA (P < .005).

The rate of major bleeding, a secondary endpoint, was also higher (12.3% vs. 8.4%) and significantly different (HR, 1.65; P < .005) for VKA versus DOACs. The rates of ischemic stroke, acute coronary syndrome, and hemorrhagic stroke were all numerically higher in patients treated with VKA than DOACs, although none of these differences reached statistical significance.
 

Residual confounding cannot be discounted

“The large number of events allowed for taking into account a higher number of potential confounders with appropriate statistical power,” according to the authors. However, they acknowledged that residual confounding cannot be eliminated by propensity matching and conceded that prospective data are needed for a definitive comparison.

In an accompanying editorial, Daniele Giacoppo, MD, a cardiologist at Alto Vicentino Hospital, Santorso, Italy, enlarged on this point . In addition to the inherent limitations of retrospective data, he also noted that data from other studies addressing the same question have been inconsistent.

Of these studies, he pointed to the ATLANTIS trial, presented 2 months ago at the annual meeting of the American College of Cardiology. This study failed to show an advantage for the DOAC apixaban over VKA in TAVR patients for the primary composite outcome of time to death, myocardial infarction, systemic emboli, valve thrombosis, or major bleeding. Although this study was not limited to patients with an indication for oral anticoagulants, Dr. Giacoppo pointed out that there was no advantage, even among the subgroup of patients who did have an indication.
 

Data are supportive in absence of trial results

In general, Dr. Giacoppo agreed that the French registry are generally supportive of DOACs over VKA in TAVR patients with an indication for oral anticoagulation, but he cautioned that blanket statements are difficult. He anticipates better information from a randomized trial called ENVISAGE-TAVI AF, which is comparing edoxaban with VKA following TAVR in atrial fibrillation patients who have an indication for oral anticoagulation, but he indicated that some individualization of choice will be needed among those high or low relative risks of thrombotic events or bleeding.

“The concerns related to DOACs after TAVR are most confined to patients without an indication for oral anticoagulation,” Dr. Giacoppo said in an interview. In patients with an indication, “oral anticoagulation alone without antithrombotic therapy significantly reduced the risk of bleeding” in several studies, he added, citing in particular the POPular TAVI trial.

Issues about when to employ – or not employ – both oral anticoagulation and antithrombotic therapy based on such factors as bleeding risk remain unresolved, but “in aggregate, waiting for additional high-quality data, the use of a DOAC in patients with an indication for oral anticoagulation who underwent TAVR seems to be safe,” Dr. Giacoppo said. He thinks that the “higher predictability of DOACS compared to vitamin K antagonists might translate into lower bleeding rates over time in a real-world, unselected population.”
 

Benefit-to-risk ratio requires attention

A similar concern about balancing risks and benefits of oral anticoagulation in TAVR patients with an indication for oral anticoagulation was emphasized by Ron Waksman, MD, associate director, division of cardiology, MedStar Washington (D.C.) Hospital Center.

“The TAVR population is elderly in general and so are at high risk for bleeding with any additional anticoagulation,” Dr. Waksman said. He cited data that bring into question the utility of using a DOAC in TAVR patients without an additional indication for anticoagulation, but he believes DOACs do make sense in those who were on and had an indication for a DOAC even before TAVR.

Patients who had atrial fibrillation or another indication “should continue to take the DOAC after TAVR. This population can be assumed to have less bleeding risk as they are vetted as safe for DOACs before their TAVR procedure,” he said.

Although mortality was the primary endpoint of the French registry evaluation, it is the bleeding risk that is a dominant concern, according to Romain Didier, MD, PhD, the first author of this study who performed this work in collaboration with Dr. Gilard.

“We really believe that VKA use in real life after TAVR, even with INR monitoring, is associated with a higher risk of bleeding as compared to DOACs,” he said. It is for this reason that “we currently use DOACs as a first choice in patients who require anticoagulant after TAVR.”

Dr. Gilard, Dr. Didier, and Dr. Giacoppo reported no potential conflicts of interest. Dr. Waksman reported financial relationships with Amgen, AstraZeneca, Boston Scientific, Cardioset, Cardiovascular Systems, Chiesi, MedAlliance, Medtronic, and Pi-Cardia.

Following a transcatheter aortic valve replacement (TAVR), direct oral anticoagulants (DOACs) are preferable to vitamin K antagonists (VKAs) in patients who are candidates for oral anticoagulants, according to data drawn from a large multicenter French TAVR registry.

When oral anticoagulation is appropriate following TAVR, such as in patients with atrial fibrillation, “DOACs are associated with improved survival and lower incidence of bleeding, compared to VKA,” reported a team of investigators led by Martine Gilard, MD, PhD, director of interventional cardiology, Brest (France) University Hospital Center.

The comparison, using propensity score matching, is not definitive, but it might be the best data currently available to support DOACs over VKA until a randomized trial is completed, according to Dr. Gilard, senior author of the newly published study.

Asked in an interview if DOACs should now be used preferentially after TAVR when patients are indicated for oral anticoagulation, Dr. Gilard replied, “My answer is yes.”

Of more than 24,000 TAVR patients in the French TAVI and FRANCE2 multicenter registries, which are linked to the French single-payer claims database (SNDS), 8,962 (36.4%) received an oral anticoagulant following their procedure. Of these, 2,180 (24.3%) received a DOAC and the remaining received VKA.

By linking data from the registries to the SNDS, outcomes were tracked. Propensity matching was employed to control for differences in baseline characteristics, including age, body mass index, functional class, diabetes, comorbidities, and past medical history.

On the primary endpoint of mortality at the end of 3 years, the rates were 35.6% and 31.2% for VKA and DOACs, respectively. This translated in a 37% greater hazard ratio for death among those treated with VKA (P < .005).

The rate of major bleeding, a secondary endpoint, was also higher (12.3% vs. 8.4%) and significantly different (HR, 1.65; P < .005) for VKA versus DOACs. The rates of ischemic stroke, acute coronary syndrome, and hemorrhagic stroke were all numerically higher in patients treated with VKA than DOACs, although none of these differences reached statistical significance.
 

Residual confounding cannot be discounted

“The large number of events allowed for taking into account a higher number of potential confounders with appropriate statistical power,” according to the authors. However, they acknowledged that residual confounding cannot be eliminated by propensity matching and conceded that prospective data are needed for a definitive comparison.

In an accompanying editorial, Daniele Giacoppo, MD, a cardiologist at Alto Vicentino Hospital, Santorso, Italy, enlarged on this point . In addition to the inherent limitations of retrospective data, he also noted that data from other studies addressing the same question have been inconsistent.

Of these studies, he pointed to the ATLANTIS trial, presented 2 months ago at the annual meeting of the American College of Cardiology. This study failed to show an advantage for the DOAC apixaban over VKA in TAVR patients for the primary composite outcome of time to death, myocardial infarction, systemic emboli, valve thrombosis, or major bleeding. Although this study was not limited to patients with an indication for oral anticoagulants, Dr. Giacoppo pointed out that there was no advantage, even among the subgroup of patients who did have an indication.
 

Data are supportive in absence of trial results

In general, Dr. Giacoppo agreed that the French registry are generally supportive of DOACs over VKA in TAVR patients with an indication for oral anticoagulation, but he cautioned that blanket statements are difficult. He anticipates better information from a randomized trial called ENVISAGE-TAVI AF, which is comparing edoxaban with VKA following TAVR in atrial fibrillation patients who have an indication for oral anticoagulation, but he indicated that some individualization of choice will be needed among those high or low relative risks of thrombotic events or bleeding.

“The concerns related to DOACs after TAVR are most confined to patients without an indication for oral anticoagulation,” Dr. Giacoppo said in an interview. In patients with an indication, “oral anticoagulation alone without antithrombotic therapy significantly reduced the risk of bleeding” in several studies, he added, citing in particular the POPular TAVI trial.

Issues about when to employ – or not employ – both oral anticoagulation and antithrombotic therapy based on such factors as bleeding risk remain unresolved, but “in aggregate, waiting for additional high-quality data, the use of a DOAC in patients with an indication for oral anticoagulation who underwent TAVR seems to be safe,” Dr. Giacoppo said. He thinks that the “higher predictability of DOACS compared to vitamin K antagonists might translate into lower bleeding rates over time in a real-world, unselected population.”
 

Benefit-to-risk ratio requires attention

A similar concern about balancing risks and benefits of oral anticoagulation in TAVR patients with an indication for oral anticoagulation was emphasized by Ron Waksman, MD, associate director, division of cardiology, MedStar Washington (D.C.) Hospital Center.

“The TAVR population is elderly in general and so are at high risk for bleeding with any additional anticoagulation,” Dr. Waksman said. He cited data that bring into question the utility of using a DOAC in TAVR patients without an additional indication for anticoagulation, but he believes DOACs do make sense in those who were on and had an indication for a DOAC even before TAVR.

Patients who had atrial fibrillation or another indication “should continue to take the DOAC after TAVR. This population can be assumed to have less bleeding risk as they are vetted as safe for DOACs before their TAVR procedure,” he said.

Although mortality was the primary endpoint of the French registry evaluation, it is the bleeding risk that is a dominant concern, according to Romain Didier, MD, PhD, the first author of this study who performed this work in collaboration with Dr. Gilard.

“We really believe that VKA use in real life after TAVR, even with INR monitoring, is associated with a higher risk of bleeding as compared to DOACs,” he said. It is for this reason that “we currently use DOACs as a first choice in patients who require anticoagulant after TAVR.”

Dr. Gilard, Dr. Didier, and Dr. Giacoppo reported no potential conflicts of interest. Dr. Waksman reported financial relationships with Amgen, AstraZeneca, Boston Scientific, Cardioset, Cardiovascular Systems, Chiesi, MedAlliance, Medtronic, and Pi-Cardia.

Only 1 child from a cohort of 45 children hospitalized with multisystem inflammatory syndrome following COVID-19 infection had persistent mild cardiac dysfunction after 9 months, according to data from patients younger than 21 years seen at a single center in 2020.

In a study published in Pediatrics, Kanwal M. Farooqi, MD, of Columbia University, New York, and colleagues provided the first report on longitudinal cardiac and immunologic outcomes in North American children hospitalized with multisystem inflammatory syndrome (MIS-C). In response to the COVID-19 pandemic, clinicians at New York–Presbyterian Hospital consolidated pediatric admissions and developed an interdisciplinary inpatient and outpatient MIS-C follow-up program to monitor cardiac and immunologic outcomes in their patients.

The study included all children younger than 21 years admitted to Columbia University Irving Medical Center/New York–Presbyterian Morgan Stanley Children’s Hospital for MIS-C in 2020. The median age of the patients was 9 years, and the median length of hospital stay was 5 days. Follow-up visits occurred at 1-4 weeks (average 2 weeks), 1-4 months (average 2 months), and 4-9 months (average 6 months) after hospital discharge. Follow-up visits included echocardiograms and measures of inflammatory markers.

Most of the children (84%) had no underlying medical conditions, but 24% presented with some level of respiratory distress or oxygen requirement, and 64% had vasodilatory shock. In addition, 80% had at least mild cardiac abnormalities and 66% had significant lymphopenia on admission.

Inflammatory profiles on admission showed elevation of C-reactive protein, ferritin, and D-dimer in 87%-98% of the patients. Consistent with cardiac involvement, 64% of the patients also had elevated troponin levels, and 91% had elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) levels.

“These parameters peaked at or shortly after admission and then gradually normalized,” the researchers said. “By the first follow-up, [C-reactive protein], troponin, and NT-proBNP had normalized in nearly all tested patients (97%-100%),” they noted.

By the first follow-up period at 1-4 weeks, all patients had normal coronary arteries, and 18% (seven patients) had mild echocardiographic findings. However, approximately one-third (32%) of the patients had persistent lymphocytosis at 1-4 weeks, and 23 of the 24 patients assessed had elevated double-negative T cells, which persisted in 96% of the patients at 1-4 months’ follow-up. However, during the last follow-up of 4-9 months, only one patient had persistent mild biventricular dysfunction and a second patient had mild mitral and tricuspid valve regurgitation.

All patients were treated with steroids and immunoglobulins (2 g/kg), as well as enoxaparin prophylaxis or low-dose aspirin and GI prophylaxis. Treatment with methylprednisolone varied based on disease severity; patients with mild presentation received 2 mg/kg per day; those with moderate presentation received a methylprednisolone pulse of 10 mg/kg per day, followed by 2 mg/kg per day; those with severe disease received methylprednisolone at 20-30 mg/kg per day for 1-3 days, followed by 2 mg/kg per day.

“Aggressive use of steroids may also explain the lower incidence of coronary artery abnormalities in our cohort,” the researchers noted.

The study findings were limited by the observational design and inability to make definitive conclusions about treatment and outcomes, as well as the evolving case definitions for MIS-C, the researchers said.

The persistence of double-negative T cells was surprising, and “likely represent a prolonged postinflammatory recovery cell population, but further study is ongoing to better define this observation,” they noted.

“Our study reveals generally encouraging medium-term outcomes, including rapid normalization of inflammatory markers and significant cardiac abnormalities in the majority of patients with MIS-C,” the researchers said. “The exact nature and potential for long-term cardiac fibrosis, exercise intolerance, or other changes remain unknown,” and long-term caution and follow-up are recommended, they concluded.
 

Cautious optimism, long-term monitoring

The study is important to provide guidance for clinicians on how to manage their patients who have been hospitalized with MIS-C, said Susan Boulter, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H.

“It was both surprising and reassuring to see that so many of the patients had positive outcomes in terms of cardiac function and that during the acute stage there were no deaths,” said Dr. Boulter. “Hospitalizations were brief, averaging just 5 days. The patients had many symptoms, but unlike adults, there was not a preponderance of underlying risk factors in this cohort of patients,” she said.

The results suggest optimism for MIS-C patients in that they generally recover, but the take-home message for clinicians is that these patients will require careful monitoring for long-term issues, Dr. Boulter said.

“These patients should be followed for years to assess long-term effects on morbidity and mortality,” Dr. Boulter emphasized.

The study was funded by Genentech. The researchers had no financial conflicts to disclose. Dr. Boulter had no financial conflicts to disclose, but serves on the Pediatric News Editorial Advisory Board.

Only 1 child from a cohort of 45 children hospitalized with multisystem inflammatory syndrome following COVID-19 infection had persistent mild cardiac dysfunction after 9 months, according to data from patients younger than 21 years seen at a single center in 2020.

In a study published in Pediatrics, Kanwal M. Farooqi, MD, of Columbia University, New York, and colleagues provided the first report on longitudinal cardiac and immunologic outcomes in North American children hospitalized with multisystem inflammatory syndrome (MIS-C). In response to the COVID-19 pandemic, clinicians at New York–Presbyterian Hospital consolidated pediatric admissions and developed an interdisciplinary inpatient and outpatient MIS-C follow-up program to monitor cardiac and immunologic outcomes in their patients.

The study included all children younger than 21 years admitted to Columbia University Irving Medical Center/New York–Presbyterian Morgan Stanley Children’s Hospital for MIS-C in 2020. The median age of the patients was 9 years, and the median length of hospital stay was 5 days. Follow-up visits occurred at 1-4 weeks (average 2 weeks), 1-4 months (average 2 months), and 4-9 months (average 6 months) after hospital discharge. Follow-up visits included echocardiograms and measures of inflammatory markers.

Most of the children (84%) had no underlying medical conditions, but 24% presented with some level of respiratory distress or oxygen requirement, and 64% had vasodilatory shock. In addition, 80% had at least mild cardiac abnormalities and 66% had significant lymphopenia on admission.

Inflammatory profiles on admission showed elevation of C-reactive protein, ferritin, and D-dimer in 87%-98% of the patients. Consistent with cardiac involvement, 64% of the patients also had elevated troponin levels, and 91% had elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) levels.

“These parameters peaked at or shortly after admission and then gradually normalized,” the researchers said. “By the first follow-up, [C-reactive protein], troponin, and NT-proBNP had normalized in nearly all tested patients (97%-100%),” they noted.

By the first follow-up period at 1-4 weeks, all patients had normal coronary arteries, and 18% (seven patients) had mild echocardiographic findings. However, approximately one-third (32%) of the patients had persistent lymphocytosis at 1-4 weeks, and 23 of the 24 patients assessed had elevated double-negative T cells, which persisted in 96% of the patients at 1-4 months’ follow-up. However, during the last follow-up of 4-9 months, only one patient had persistent mild biventricular dysfunction and a second patient had mild mitral and tricuspid valve regurgitation.

All patients were treated with steroids and immunoglobulins (2 g/kg), as well as enoxaparin prophylaxis or low-dose aspirin and GI prophylaxis. Treatment with methylprednisolone varied based on disease severity; patients with mild presentation received 2 mg/kg per day; those with moderate presentation received a methylprednisolone pulse of 10 mg/kg per day, followed by 2 mg/kg per day; those with severe disease received methylprednisolone at 20-30 mg/kg per day for 1-3 days, followed by 2 mg/kg per day.

“Aggressive use of steroids may also explain the lower incidence of coronary artery abnormalities in our cohort,” the researchers noted.

The study findings were limited by the observational design and inability to make definitive conclusions about treatment and outcomes, as well as the evolving case definitions for MIS-C, the researchers said.

The persistence of double-negative T cells was surprising, and “likely represent a prolonged postinflammatory recovery cell population, but further study is ongoing to better define this observation,” they noted.

“Our study reveals generally encouraging medium-term outcomes, including rapid normalization of inflammatory markers and significant cardiac abnormalities in the majority of patients with MIS-C,” the researchers said. “The exact nature and potential for long-term cardiac fibrosis, exercise intolerance, or other changes remain unknown,” and long-term caution and follow-up are recommended, they concluded.
 

Cautious optimism, long-term monitoring

The study is important to provide guidance for clinicians on how to manage their patients who have been hospitalized with MIS-C, said Susan Boulter, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H.

“It was both surprising and reassuring to see that so many of the patients had positive outcomes in terms of cardiac function and that during the acute stage there were no deaths,” said Dr. Boulter. “Hospitalizations were brief, averaging just 5 days. The patients had many symptoms, but unlike adults, there was not a preponderance of underlying risk factors in this cohort of patients,” she said.

The results suggest optimism for MIS-C patients in that they generally recover, but the take-home message for clinicians is that these patients will require careful monitoring for long-term issues, Dr. Boulter said.

“These patients should be followed for years to assess long-term effects on morbidity and mortality,” Dr. Boulter emphasized.

The study was funded by Genentech. The researchers had no financial conflicts to disclose. Dr. Boulter had no financial conflicts to disclose, but serves on the Pediatric News Editorial Advisory Board.

Only 1 child from a cohort of 45 children hospitalized with multisystem inflammatory syndrome following COVID-19 infection had persistent mild cardiac dysfunction after 9 months, according to data from patients younger than 21 years seen at a single center in 2020.

In a study published in Pediatrics, Kanwal M. Farooqi, MD, of Columbia University, New York, and colleagues provided the first report on longitudinal cardiac and immunologic outcomes in North American children hospitalized with multisystem inflammatory syndrome (MIS-C). In response to the COVID-19 pandemic, clinicians at New York–Presbyterian Hospital consolidated pediatric admissions and developed an interdisciplinary inpatient and outpatient MIS-C follow-up program to monitor cardiac and immunologic outcomes in their patients.

The study included all children younger than 21 years admitted to Columbia University Irving Medical Center/New York–Presbyterian Morgan Stanley Children’s Hospital for MIS-C in 2020. The median age of the patients was 9 years, and the median length of hospital stay was 5 days. Follow-up visits occurred at 1-4 weeks (average 2 weeks), 1-4 months (average 2 months), and 4-9 months (average 6 months) after hospital discharge. Follow-up visits included echocardiograms and measures of inflammatory markers.

Most of the children (84%) had no underlying medical conditions, but 24% presented with some level of respiratory distress or oxygen requirement, and 64% had vasodilatory shock. In addition, 80% had at least mild cardiac abnormalities and 66% had significant lymphopenia on admission.

Inflammatory profiles on admission showed elevation of C-reactive protein, ferritin, and D-dimer in 87%-98% of the patients. Consistent with cardiac involvement, 64% of the patients also had elevated troponin levels, and 91% had elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) levels.

“These parameters peaked at or shortly after admission and then gradually normalized,” the researchers said. “By the first follow-up, [C-reactive protein], troponin, and NT-proBNP had normalized in nearly all tested patients (97%-100%),” they noted.

By the first follow-up period at 1-4 weeks, all patients had normal coronary arteries, and 18% (seven patients) had mild echocardiographic findings. However, approximately one-third (32%) of the patients had persistent lymphocytosis at 1-4 weeks, and 23 of the 24 patients assessed had elevated double-negative T cells, which persisted in 96% of the patients at 1-4 months’ follow-up. However, during the last follow-up of 4-9 months, only one patient had persistent mild biventricular dysfunction and a second patient had mild mitral and tricuspid valve regurgitation.

All patients were treated with steroids and immunoglobulins (2 g/kg), as well as enoxaparin prophylaxis or low-dose aspirin and GI prophylaxis. Treatment with methylprednisolone varied based on disease severity; patients with mild presentation received 2 mg/kg per day; those with moderate presentation received a methylprednisolone pulse of 10 mg/kg per day, followed by 2 mg/kg per day; those with severe disease received methylprednisolone at 20-30 mg/kg per day for 1-3 days, followed by 2 mg/kg per day.

“Aggressive use of steroids may also explain the lower incidence of coronary artery abnormalities in our cohort,” the researchers noted.

The study findings were limited by the observational design and inability to make definitive conclusions about treatment and outcomes, as well as the evolving case definitions for MIS-C, the researchers said.

The persistence of double-negative T cells was surprising, and “likely represent a prolonged postinflammatory recovery cell population, but further study is ongoing to better define this observation,” they noted.

“Our study reveals generally encouraging medium-term outcomes, including rapid normalization of inflammatory markers and significant cardiac abnormalities in the majority of patients with MIS-C,” the researchers said. “The exact nature and potential for long-term cardiac fibrosis, exercise intolerance, or other changes remain unknown,” and long-term caution and follow-up are recommended, they concluded.
 

Cautious optimism, long-term monitoring

The study is important to provide guidance for clinicians on how to manage their patients who have been hospitalized with MIS-C, said Susan Boulter, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H.

“It was both surprising and reassuring to see that so many of the patients had positive outcomes in terms of cardiac function and that during the acute stage there were no deaths,” said Dr. Boulter. “Hospitalizations were brief, averaging just 5 days. The patients had many symptoms, but unlike adults, there was not a preponderance of underlying risk factors in this cohort of patients,” she said.

The results suggest optimism for MIS-C patients in that they generally recover, but the take-home message for clinicians is that these patients will require careful monitoring for long-term issues, Dr. Boulter said.

“These patients should be followed for years to assess long-term effects on morbidity and mortality,” Dr. Boulter emphasized.

The study was funded by Genentech. The researchers had no financial conflicts to disclose. Dr. Boulter had no financial conflicts to disclose, but serves on the Pediatric News Editorial Advisory Board.

St. Jude Medical, now part of Abbott Laboratories, will pay the American government $27 million to settle allegations that it knowingly sold defective implantable cardiac defibrillators to health care facilities, which were implanted into patients, causing injuries and two deaths, the U.S. Department of Justice (DOJ) has announced.

“Medical device manufacturers have an obligation to be truthful with the Food and Drug Administration, and the U.S. government will not pay for devices that are unsafe and risk injury or death,” Jonathan F. Lenzner, Acting U.S. Attorney for the District of Maryland, said in a July 8 statement.

“The government contends that St. Jude knowingly caused the submission of false claims and failed to inform the FDA with critical information about prior injuries and a death which, had the FDA been made aware, would have led to a recall,” Mr. Lenzner added.

Those claims were submitted to the Medicare, TRICARE, and Federal Employees Health Benefits programs, according to the settlement agreement.

“The U.S. Attorney’s Office is committed to protecting Medicare and other federal health care programs from fraud, and in doing so, strengthen[ing] patient safety,” Mr. Lenzner said.
 

Premature battery depletion

The government alleges that St. Jude failed to disclose “serious adverse health events” related to premature battery depletion of certain models of its Fortify, Fortify Assura, Quadra, and Unify implantable defibrillators.

The government further alleges that, by 2013, St. Jude knew that lithium clusters could form on the batteries, causing them to short and run out of power. But it took until late 2014 for St. Jude to ask the FDA to approve a change to prevent lithium clusters from draining the battery.

And at this point, St. Jude told the FDA that “no serious injury, permanent harm, or deaths have been reported associated with this” issue, the government alleges.

However, according to the government’s allegations, St. Jude was aware at that time of two reported serious injuries and one death associated with the faulty batteries and continued to distribute devices that had been manufactured without the new design.

Not until August 2016 did St. Jude inform the FDA that the number of premature battery depletion events had increased to 729, including two deaths and 29 events associated with loss of pacing, the government alleges.

In October 2016, St. Jude issued a medical advisory regarding the battery problem, which the FDA classified as a Class I recall, the most serious type.

After the recall, St. Jude no longer sold the older devices, but thousands of them had been implanted into patients between November 2014 and October 2016.

In September 2017, as reported by this news organization, a nationwide class-action lawsuit was filed against St. Jude Medical and parent company Abbott Laboratories alleging that, despite knowing about a battery-depletion defect in some of its cardiac defibrillators as early as 2011, St. Jude failed to adequately report the risk and waited nearly 5 years before issuing a recall.

“To ensure the health and safety of patients, manufacturers of implantable cardiac devices must be transparent when communicating with the government about safety issues and incidents,” Acting Assistant Attorney General Brian Boynton, from the DOJ’s Civil Division, said in the DOJ statement announcing the settlement.

“We will hold accountable those companies whose conduct violates the law and puts patients’ health at risk,” Mr. Boynton said.

The civil settlement includes the resolution of claims brought under the qui tam, or whistleblower, provisions of the False Claims Act by Debbie Burke, a patient who received one of the devices that was subject to recall.

The claims resolved by the settlement are allegations only; there has been no determination of liability, the DOJ noted. St. Jude denies the allegations raised in the lawsuit.

A version of this article first appeared on Medscape.com.

St. Jude Medical, now part of Abbott Laboratories, will pay the American government $27 million to settle allegations that it knowingly sold defective implantable cardiac defibrillators to health care facilities, which were implanted into patients, causing injuries and two deaths, the U.S. Department of Justice (DOJ) has announced.

“Medical device manufacturers have an obligation to be truthful with the Food and Drug Administration, and the U.S. government will not pay for devices that are unsafe and risk injury or death,” Jonathan F. Lenzner, Acting U.S. Attorney for the District of Maryland, said in a July 8 statement.

“The government contends that St. Jude knowingly caused the submission of false claims and failed to inform the FDA with critical information about prior injuries and a death which, had the FDA been made aware, would have led to a recall,” Mr. Lenzner added.

Those claims were submitted to the Medicare, TRICARE, and Federal Employees Health Benefits programs, according to the settlement agreement.

“The U.S. Attorney’s Office is committed to protecting Medicare and other federal health care programs from fraud, and in doing so, strengthen[ing] patient safety,” Mr. Lenzner said.
 

Premature battery depletion

The government alleges that St. Jude failed to disclose “serious adverse health events” related to premature battery depletion of certain models of its Fortify, Fortify Assura, Quadra, and Unify implantable defibrillators.

The government further alleges that, by 2013, St. Jude knew that lithium clusters could form on the batteries, causing them to short and run out of power. But it took until late 2014 for St. Jude to ask the FDA to approve a change to prevent lithium clusters from draining the battery.

And at this point, St. Jude told the FDA that “no serious injury, permanent harm, or deaths have been reported associated with this” issue, the government alleges.

However, according to the government’s allegations, St. Jude was aware at that time of two reported serious injuries and one death associated with the faulty batteries and continued to distribute devices that had been manufactured without the new design.

Not until August 2016 did St. Jude inform the FDA that the number of premature battery depletion events had increased to 729, including two deaths and 29 events associated with loss of pacing, the government alleges.

In October 2016, St. Jude issued a medical advisory regarding the battery problem, which the FDA classified as a Class I recall, the most serious type.

After the recall, St. Jude no longer sold the older devices, but thousands of them had been implanted into patients between November 2014 and October 2016.

In September 2017, as reported by this news organization, a nationwide class-action lawsuit was filed against St. Jude Medical and parent company Abbott Laboratories alleging that, despite knowing about a battery-depletion defect in some of its cardiac defibrillators as early as 2011, St. Jude failed to adequately report the risk and waited nearly 5 years before issuing a recall.

“To ensure the health and safety of patients, manufacturers of implantable cardiac devices must be transparent when communicating with the government about safety issues and incidents,” Acting Assistant Attorney General Brian Boynton, from the DOJ’s Civil Division, said in the DOJ statement announcing the settlement.

“We will hold accountable those companies whose conduct violates the law and puts patients’ health at risk,” Mr. Boynton said.

The civil settlement includes the resolution of claims brought under the qui tam, or whistleblower, provisions of the False Claims Act by Debbie Burke, a patient who received one of the devices that was subject to recall.

The claims resolved by the settlement are allegations only; there has been no determination of liability, the DOJ noted. St. Jude denies the allegations raised in the lawsuit.

A version of this article first appeared on Medscape.com.

St. Jude Medical, now part of Abbott Laboratories, will pay the American government $27 million to settle allegations that it knowingly sold defective implantable cardiac defibrillators to health care facilities, which were implanted into patients, causing injuries and two deaths, the U.S. Department of Justice (DOJ) has announced.

“Medical device manufacturers have an obligation to be truthful with the Food and Drug Administration, and the U.S. government will not pay for devices that are unsafe and risk injury or death,” Jonathan F. Lenzner, Acting U.S. Attorney for the District of Maryland, said in a July 8 statement.

“The government contends that St. Jude knowingly caused the submission of false claims and failed to inform the FDA with critical information about prior injuries and a death which, had the FDA been made aware, would have led to a recall,” Mr. Lenzner added.

Those claims were submitted to the Medicare, TRICARE, and Federal Employees Health Benefits programs, according to the settlement agreement.

“The U.S. Attorney’s Office is committed to protecting Medicare and other federal health care programs from fraud, and in doing so, strengthen[ing] patient safety,” Mr. Lenzner said.
 

Premature battery depletion

The government alleges that St. Jude failed to disclose “serious adverse health events” related to premature battery depletion of certain models of its Fortify, Fortify Assura, Quadra, and Unify implantable defibrillators.

The government further alleges that, by 2013, St. Jude knew that lithium clusters could form on the batteries, causing them to short and run out of power. But it took until late 2014 for St. Jude to ask the FDA to approve a change to prevent lithium clusters from draining the battery.

And at this point, St. Jude told the FDA that “no serious injury, permanent harm, or deaths have been reported associated with this” issue, the government alleges.

However, according to the government’s allegations, St. Jude was aware at that time of two reported serious injuries and one death associated with the faulty batteries and continued to distribute devices that had been manufactured without the new design.

Not until August 2016 did St. Jude inform the FDA that the number of premature battery depletion events had increased to 729, including two deaths and 29 events associated with loss of pacing, the government alleges.

In October 2016, St. Jude issued a medical advisory regarding the battery problem, which the FDA classified as a Class I recall, the most serious type.

After the recall, St. Jude no longer sold the older devices, but thousands of them had been implanted into patients between November 2014 and October 2016.

In September 2017, as reported by this news organization, a nationwide class-action lawsuit was filed against St. Jude Medical and parent company Abbott Laboratories alleging that, despite knowing about a battery-depletion defect in some of its cardiac defibrillators as early as 2011, St. Jude failed to adequately report the risk and waited nearly 5 years before issuing a recall.

“To ensure the health and safety of patients, manufacturers of implantable cardiac devices must be transparent when communicating with the government about safety issues and incidents,” Acting Assistant Attorney General Brian Boynton, from the DOJ’s Civil Division, said in the DOJ statement announcing the settlement.

“We will hold accountable those companies whose conduct violates the law and puts patients’ health at risk,” Mr. Boynton said.

The civil settlement includes the resolution of claims brought under the qui tam, or whistleblower, provisions of the False Claims Act by Debbie Burke, a patient who received one of the devices that was subject to recall.

The claims resolved by the settlement are allegations only; there has been no determination of liability, the DOJ noted. St. Jude denies the allegations raised in the lawsuit.

A version of this article first appeared on Medscape.com.

Individuals of South Asian ancestry face twice the risk of heart disease, compared with individuals of European descent, yet existing risk calculators fail to account for this disparity, according to the results of a new study.

These findings confirm previous reports and practice guidelines that identify South Asian ancestry as a risk enhancer for atherosclerotic cardiovascular disease (ASCVD), suggesting that earlier heart disease screening and prevention is warranted in this patient population, lead author Aniruddh P. Patel, MD, research fellow at the Center for Genomic Medicine, Massachusetts General Hospital, Boston, and colleagues said.

“Previous studies in multiple countries have estimated a 1.7- to 4-fold higher risk of ASCVD among South Asian individuals, compared with other ancestries, but have important potential limitations,” Dr. Patel and colleagues wrote in the paper on their prospective cohort study, published in Circulation.

The INTERHEART case-control study, for example, which assessed risk factors for acute myocardial infarction among more than 15,000 cases from 52 countries, is now 2 decades old, and “may not reflect recent advances in cardiovascular disease prevention,” the investigators wrote.

Most studies in the area have been small and retrospective, they added, and have not adequately assessed emerging risk factors, such as prediabetes, which appear to play a relatively greater role in the development of heart disease among South Asians.
 

Methods and results

To address this knowledge gap, Dr. Patel and colleagues analyzed data from the UK Biobank prospective cohort study, including 449,349 middle-aged participants of European ancestry and 8,124 similarly aged participants of South Asian descent who did not have heart disease upon enrollment. Respective rates of incident ASCVD (i.e., MI, ischemic stroke, or coronary revascularization) were analyzed in the context of a variety of lifestyle, anthropometric, and clinical factors.

After a median follow-up of 11.1 years, individuals of South Asian descent had an incident ASCVD rate of 6.8%, compared with 4.4% for individuals of European descent, representing twice the relative risk (adjusted hazard ratio, 2.03; 95% CI, 1.86-2.22; P < .001). Even after accounting for all covariates, risk of ASCVD remained 45% higher for South Asian individuals (aHR, 1.45; 95% CI, 1.28-1.65; P < .001). This elevation in risk was not captured by existing risk calculators, including the American College of Cardiology/American Heart Association Pooled Cohort Equations, or the QRISK3 equations.

The findings were “largely consistent across a range of age, sex, and clinical subgroups,” and “confirm and extend previous reports that hypertension, diabetes, and central adiposity are the leading associations in this observed disparity,” the investigators wrote.
 

Two diabetes subtypes are more prevalent in South Asians

Hypertension, diabetes, and central adiposity do not fully explain South Asians’ higher risk for ASCVD, wrote Namratha R. Kandula, MD, of Northwestern University Medical Center, Chicago, and Alka M. Kanaya, MD, of the University of California, San Francisco, in an accompanying editorial published in Circulation.

Some of the undetected risk may stem from unique diabetes disease factors, Dr. Kandula and Dr. Kanaya added.

“Newer data have demonstrated distinct subtypes of type 2 diabetes, with South Asians having a higher prevalence of both a severe insulin resistant with obesity subtype and a less recognized severe insulin deficient subtype,” they wrote. “Importantly, both of these more prevalent diabetes subtypes in South Asians were associated with a higher incidence of coronary artery calcium, a marker of subclinical atherosclerosis and strong predictor of future ASCVD, compared to other diabetes subtypes.”
 

Diabetes rate is higher for South Asians in the U.S.

Although the present study was conducted in the United Kingdom, the findings likely apply to individuals of South Asian ancestry living in the United States, according to principal author Amit V. Khera, MD, associate director of the precision medicine unit at the Center for Genomic Medicine, Massachusetts General Hospital.

“There are already more than 5 million individuals of South Asian ancestry in the U.S. and this represents one of the fastest-growing ethnic subgroups,” Dr. Khera said in an interview. “As in our study of individuals in the U.K., South Asians in the U.S. suffer from diabetes at much higher rates – 23% versus 12% – and this often occurs even in the absence of obesity.”

Dr. Khera noted that the 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease identify South Asian ancestry as a risk-enhancing factor, calling this a “stopgap measure.” More work is needed, he said, in the research arena and in the clinic.
 

Zero South Asians included in studies used to develop risk estimator

“I think the first step is to simply acknowledge that the risk estimators we use in clinical practice have important limitations when it comes to diverse patient populations,” Dr. Khera said in an interview. “We saw this in our study, where – despite a more than doubling of risk – the predicted risk based on the equations used in primary care showed no difference. This risk estimator was developed based on legacy cohort studies, in [which] zero South Asians were included. Despite important differences across race/ethnicity, the current state-of-the-art in the U.S. is to use one equation for Black individuals and another for all other ethnicities.”

Experts suggest steps for reducing heart disease risk

While risk modeling remains suboptimal, Dr. Khera suggested that clinicians can take immediate steps to reduce the risk of heart disease among individuals with South Asian ancestry.

“Despite all of the uncertainty – we still don’t have a complete understanding of why the risk is so high – there are still several things primary care doctors can do for their patients,” Dr. Khera said.

Foremost, he recommended lifestyle and dietary counseling.

“Dietary counseling is particularly effective if put in the context of cultural norms,” Dr. Khera said. “Many South Asians consider fruit juices or white rice to be healthy, when they lead to rapid spikes in blood sugar.”

Dr. Khera also advised earlier heart disease screening, such as coronary calcium scanning “sometime between age 40-50 years,” noting that positive test results may motivate patients to start or adhere to medications, such as cholesterol-lowering therapies. If necessary, clinicians can also refer to heart centers for South Asian patients, which are becoming increasingly common.

According to Cheryl A.M. Anderson, PhD, chair of the AHA’s Council on Epidemiology and Prevention, and professor and dean of the Herbert Wertheim School of Public Health and Human Longevity Science at the University of California, San Diego, the current study suggests that heart disease management strategies for South Asian patients may be lacking.

“We have had a tradition of preventing or trying to treat heart disease in a fashion that doesn’t yet account for the increased risk that might be prevalent in those of South Asian ancestry,” Dr. Anderson said in an interview.

She suggested that improving associated risk-analysis tools could be beneficial, although the tools themselves, in the context of race or ethnicity, may present their own risks.

“We want to be mindful of potential adverse implications from having everything linked to one’s ancestry, which I think this tool doesn’t do,” Dr. Anderson said, referring to the AHA/ACC Pooled Cohort Equations. “But in sort of the bigger picture of things, we always want to expand and refine our toolkit.”

According to Rajesh Dash, MD, PhD, associate professor, cardiologist, and director of the South Asian Translational Heart Initiative (SSATHI) Prevention Clinic and CardioClick Telemedicine Clinic at Stanford (Calif.) HealthCare, the science supports more active risk mitigation strategies for South Asian patients, and the AHA and the ACC “are the two entities that need to lead the way.”

“Certainly the American Heart Association and the American College of Cardiology should be taking a more active leadership role in this,” Dr. Dash said in an interview.

In 2018, the AHA issued a scientific statement about the elevated risk of ASCVD among South Asian individuals, “but it did not rise to the level of specific recommendations, and did not necessarily go as far as to incorporate new screening parameters for that population,” Dr. Dash said. He also noted that the most recent AHA/ACC guideline identifies South Asian ancestry as a risk-enhancing feature, a statement similarly lacking in actionable value.

“That does not definitively lead someone like a primary care physician to a decision to start a statin, or to be more aggressive with a diagnostic workup, like a stress test, for instance, for a patient who they otherwise would not have done one in had they not been South Asian,” Dr. Dash said.

The steps taken by the AHA and the ACC are “a healthy step forward,” he noted, “but not nearly the degree of attention or vigilance that is required, as well as the level of action that is required to change the narrative for the population.”

At the SSATHI Prevention Clinic, Dr. Dash and colleagues aren’t waiting for the narrative to change, and are already taking a more aggressive approach.

The clinic has an average patient age of 41 years, “easily 15 years younger than the average age in most cardiology clinics,” Dr. Dash said, based on the fact that approximately two-thirds of heart attacks in South Asian individuals occur under the age of 55. “We have to look earlier.”

The SSATHI Prevention Clinic screens for both traditional and emerging risk factors, and Dr. Dash suggested that primary care doctors should do the same.

“If you have a South Asian patient as a primary care physician, you should be aggressively looking for risk factors, traditional ones to start, like elevated cholesterol, hypertension, diabetes, or – and I would argue strongly – prediabetes or insulin resistance.”

Dr. Dash also recommended looking into family history, and considering screening for inflammatory biomarkers, the latter of which are commonly elevated at an earlier age among South Asian individuals, and may have a relatively greater prognostic impact.

To encourage broader implementation of this kind of approach, Dr. Dash called for more large-scale studies. Ideally, these would be randomized clinical trials, but, realistically, real-world datasets may be the answer.

The study was supported by the National Heart, Lung, and Blood Institute; the Broad Institute at MIT and Harvard; the National Human Genome Research Institute; and others. The investigators disclosed relationships with IBM Research, Sanofi, Amgen, and others. Dr. Dash disclosed relationships with HealthPals and AstraZeneca. Dr. Anderson reported no relevant conflicts of interest.

Individuals of South Asian ancestry face twice the risk of heart disease, compared with individuals of European descent, yet existing risk calculators fail to account for this disparity, according to the results of a new study.

These findings confirm previous reports and practice guidelines that identify South Asian ancestry as a risk enhancer for atherosclerotic cardiovascular disease (ASCVD), suggesting that earlier heart disease screening and prevention is warranted in this patient population, lead author Aniruddh P. Patel, MD, research fellow at the Center for Genomic Medicine, Massachusetts General Hospital, Boston, and colleagues said.

“Previous studies in multiple countries have estimated a 1.7- to 4-fold higher risk of ASCVD among South Asian individuals, compared with other ancestries, but have important potential limitations,” Dr. Patel and colleagues wrote in the paper on their prospective cohort study, published in Circulation.

The INTERHEART case-control study, for example, which assessed risk factors for acute myocardial infarction among more than 15,000 cases from 52 countries, is now 2 decades old, and “may not reflect recent advances in cardiovascular disease prevention,” the investigators wrote.

Most studies in the area have been small and retrospective, they added, and have not adequately assessed emerging risk factors, such as prediabetes, which appear to play a relatively greater role in the development of heart disease among South Asians.
 

Methods and results

To address this knowledge gap, Dr. Patel and colleagues analyzed data from the UK Biobank prospective cohort study, including 449,349 middle-aged participants of European ancestry and 8,124 similarly aged participants of South Asian descent who did not have heart disease upon enrollment. Respective rates of incident ASCVD (i.e., MI, ischemic stroke, or coronary revascularization) were analyzed in the context of a variety of lifestyle, anthropometric, and clinical factors.

After a median follow-up of 11.1 years, individuals of South Asian descent had an incident ASCVD rate of 6.8%, compared with 4.4% for individuals of European descent, representing twice the relative risk (adjusted hazard ratio, 2.03; 95% CI, 1.86-2.22; P < .001). Even after accounting for all covariates, risk of ASCVD remained 45% higher for South Asian individuals (aHR, 1.45; 95% CI, 1.28-1.65; P < .001). This elevation in risk was not captured by existing risk calculators, including the American College of Cardiology/American Heart Association Pooled Cohort Equations, or the QRISK3 equations.

The findings were “largely consistent across a range of age, sex, and clinical subgroups,” and “confirm and extend previous reports that hypertension, diabetes, and central adiposity are the leading associations in this observed disparity,” the investigators wrote.
 

Two diabetes subtypes are more prevalent in South Asians

Hypertension, diabetes, and central adiposity do not fully explain South Asians’ higher risk for ASCVD, wrote Namratha R. Kandula, MD, of Northwestern University Medical Center, Chicago, and Alka M. Kanaya, MD, of the University of California, San Francisco, in an accompanying editorial published in Circulation.

Some of the undetected risk may stem from unique diabetes disease factors, Dr. Kandula and Dr. Kanaya added.

“Newer data have demonstrated distinct subtypes of type 2 diabetes, with South Asians having a higher prevalence of both a severe insulin resistant with obesity subtype and a less recognized severe insulin deficient subtype,” they wrote. “Importantly, both of these more prevalent diabetes subtypes in South Asians were associated with a higher incidence of coronary artery calcium, a marker of subclinical atherosclerosis and strong predictor of future ASCVD, compared to other diabetes subtypes.”
 

Diabetes rate is higher for South Asians in the U.S.

Although the present study was conducted in the United Kingdom, the findings likely apply to individuals of South Asian ancestry living in the United States, according to principal author Amit V. Khera, MD, associate director of the precision medicine unit at the Center for Genomic Medicine, Massachusetts General Hospital.

“There are already more than 5 million individuals of South Asian ancestry in the U.S. and this represents one of the fastest-growing ethnic subgroups,” Dr. Khera said in an interview. “As in our study of individuals in the U.K., South Asians in the U.S. suffer from diabetes at much higher rates – 23% versus 12% – and this often occurs even in the absence of obesity.”

Dr. Khera noted that the 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease identify South Asian ancestry as a risk-enhancing factor, calling this a “stopgap measure.” More work is needed, he said, in the research arena and in the clinic.
 

Zero South Asians included in studies used to develop risk estimator

“I think the first step is to simply acknowledge that the risk estimators we use in clinical practice have important limitations when it comes to diverse patient populations,” Dr. Khera said in an interview. “We saw this in our study, where – despite a more than doubling of risk – the predicted risk based on the equations used in primary care showed no difference. This risk estimator was developed based on legacy cohort studies, in [which] zero South Asians were included. Despite important differences across race/ethnicity, the current state-of-the-art in the U.S. is to use one equation for Black individuals and another for all other ethnicities.”

Experts suggest steps for reducing heart disease risk

While risk modeling remains suboptimal, Dr. Khera suggested that clinicians can take immediate steps to reduce the risk of heart disease among individuals with South Asian ancestry.

“Despite all of the uncertainty – we still don’t have a complete understanding of why the risk is so high – there are still several things primary care doctors can do for their patients,” Dr. Khera said.

Foremost, he recommended lifestyle and dietary counseling.

“Dietary counseling is particularly effective if put in the context of cultural norms,” Dr. Khera said. “Many South Asians consider fruit juices or white rice to be healthy, when they lead to rapid spikes in blood sugar.”

Dr. Khera also advised earlier heart disease screening, such as coronary calcium scanning “sometime between age 40-50 years,” noting that positive test results may motivate patients to start or adhere to medications, such as cholesterol-lowering therapies. If necessary, clinicians can also refer to heart centers for South Asian patients, which are becoming increasingly common.

According to Cheryl A.M. Anderson, PhD, chair of the AHA’s Council on Epidemiology and Prevention, and professor and dean of the Herbert Wertheim School of Public Health and Human Longevity Science at the University of California, San Diego, the current study suggests that heart disease management strategies for South Asian patients may be lacking.

“We have had a tradition of preventing or trying to treat heart disease in a fashion that doesn’t yet account for the increased risk that might be prevalent in those of South Asian ancestry,” Dr. Anderson said in an interview.

She suggested that improving associated risk-analysis tools could be beneficial, although the tools themselves, in the context of race or ethnicity, may present their own risks.

“We want to be mindful of potential adverse implications from having everything linked to one’s ancestry, which I think this tool doesn’t do,” Dr. Anderson said, referring to the AHA/ACC Pooled Cohort Equations. “But in sort of the bigger picture of things, we always want to expand and refine our toolkit.”

According to Rajesh Dash, MD, PhD, associate professor, cardiologist, and director of the South Asian Translational Heart Initiative (SSATHI) Prevention Clinic and CardioClick Telemedicine Clinic at Stanford (Calif.) HealthCare, the science supports more active risk mitigation strategies for South Asian patients, and the AHA and the ACC “are the two entities that need to lead the way.”

“Certainly the American Heart Association and the American College of Cardiology should be taking a more active leadership role in this,” Dr. Dash said in an interview.

In 2018, the AHA issued a scientific statement about the elevated risk of ASCVD among South Asian individuals, “but it did not rise to the level of specific recommendations, and did not necessarily go as far as to incorporate new screening parameters for that population,” Dr. Dash said. He also noted that the most recent AHA/ACC guideline identifies South Asian ancestry as a risk-enhancing feature, a statement similarly lacking in actionable value.

“That does not definitively lead someone like a primary care physician to a decision to start a statin, or to be more aggressive with a diagnostic workup, like a stress test, for instance, for a patient who they otherwise would not have done one in had they not been South Asian,” Dr. Dash said.

The steps taken by the AHA and the ACC are “a healthy step forward,” he noted, “but not nearly the degree of attention or vigilance that is required, as well as the level of action that is required to change the narrative for the population.”

At the SSATHI Prevention Clinic, Dr. Dash and colleagues aren’t waiting for the narrative to change, and are already taking a more aggressive approach.

The clinic has an average patient age of 41 years, “easily 15 years younger than the average age in most cardiology clinics,” Dr. Dash said, based on the fact that approximately two-thirds of heart attacks in South Asian individuals occur under the age of 55. “We have to look earlier.”

The SSATHI Prevention Clinic screens for both traditional and emerging risk factors, and Dr. Dash suggested that primary care doctors should do the same.

“If you have a South Asian patient as a primary care physician, you should be aggressively looking for risk factors, traditional ones to start, like elevated cholesterol, hypertension, diabetes, or – and I would argue strongly – prediabetes or insulin resistance.”

Dr. Dash also recommended looking into family history, and considering screening for inflammatory biomarkers, the latter of which are commonly elevated at an earlier age among South Asian individuals, and may have a relatively greater prognostic impact.

To encourage broader implementation of this kind of approach, Dr. Dash called for more large-scale studies. Ideally, these would be randomized clinical trials, but, realistically, real-world datasets may be the answer.

The study was supported by the National Heart, Lung, and Blood Institute; the Broad Institute at MIT and Harvard; the National Human Genome Research Institute; and others. The investigators disclosed relationships with IBM Research, Sanofi, Amgen, and others. Dr. Dash disclosed relationships with HealthPals and AstraZeneca. Dr. Anderson reported no relevant conflicts of interest.

Individuals of South Asian ancestry face twice the risk of heart disease, compared with individuals of European descent, yet existing risk calculators fail to account for this disparity, according to the results of a new study.

These findings confirm previous reports and practice guidelines that identify South Asian ancestry as a risk enhancer for atherosclerotic cardiovascular disease (ASCVD), suggesting that earlier heart disease screening and prevention is warranted in this patient population, lead author Aniruddh P. Patel, MD, research fellow at the Center for Genomic Medicine, Massachusetts General Hospital, Boston, and colleagues said.

“Previous studies in multiple countries have estimated a 1.7- to 4-fold higher risk of ASCVD among South Asian individuals, compared with other ancestries, but have important potential limitations,” Dr. Patel and colleagues wrote in the paper on their prospective cohort study, published in Circulation.

The INTERHEART case-control study, for example, which assessed risk factors for acute myocardial infarction among more than 15,000 cases from 52 countries, is now 2 decades old, and “may not reflect recent advances in cardiovascular disease prevention,” the investigators wrote.

Most studies in the area have been small and retrospective, they added, and have not adequately assessed emerging risk factors, such as prediabetes, which appear to play a relatively greater role in the development of heart disease among South Asians.
 

Methods and results

To address this knowledge gap, Dr. Patel and colleagues analyzed data from the UK Biobank prospective cohort study, including 449,349 middle-aged participants of European ancestry and 8,124 similarly aged participants of South Asian descent who did not have heart disease upon enrollment. Respective rates of incident ASCVD (i.e., MI, ischemic stroke, or coronary revascularization) were analyzed in the context of a variety of lifestyle, anthropometric, and clinical factors.

After a median follow-up of 11.1 years, individuals of South Asian descent had an incident ASCVD rate of 6.8%, compared with 4.4% for individuals of European descent, representing twice the relative risk (adjusted hazard ratio, 2.03; 95% CI, 1.86-2.22; P < .001). Even after accounting for all covariates, risk of ASCVD remained 45% higher for South Asian individuals (aHR, 1.45; 95% CI, 1.28-1.65; P < .001). This elevation in risk was not captured by existing risk calculators, including the American College of Cardiology/American Heart Association Pooled Cohort Equations, or the QRISK3 equations.

The findings were “largely consistent across a range of age, sex, and clinical subgroups,” and “confirm and extend previous reports that hypertension, diabetes, and central adiposity are the leading associations in this observed disparity,” the investigators wrote.
 

Two diabetes subtypes are more prevalent in South Asians

Hypertension, diabetes, and central adiposity do not fully explain South Asians’ higher risk for ASCVD, wrote Namratha R. Kandula, MD, of Northwestern University Medical Center, Chicago, and Alka M. Kanaya, MD, of the University of California, San Francisco, in an accompanying editorial published in Circulation.

Some of the undetected risk may stem from unique diabetes disease factors, Dr. Kandula and Dr. Kanaya added.

“Newer data have demonstrated distinct subtypes of type 2 diabetes, with South Asians having a higher prevalence of both a severe insulin resistant with obesity subtype and a less recognized severe insulin deficient subtype,” they wrote. “Importantly, both of these more prevalent diabetes subtypes in South Asians were associated with a higher incidence of coronary artery calcium, a marker of subclinical atherosclerosis and strong predictor of future ASCVD, compared to other diabetes subtypes.”
 

Diabetes rate is higher for South Asians in the U.S.

Although the present study was conducted in the United Kingdom, the findings likely apply to individuals of South Asian ancestry living in the United States, according to principal author Amit V. Khera, MD, associate director of the precision medicine unit at the Center for Genomic Medicine, Massachusetts General Hospital.

“There are already more than 5 million individuals of South Asian ancestry in the U.S. and this represents one of the fastest-growing ethnic subgroups,” Dr. Khera said in an interview. “As in our study of individuals in the U.K., South Asians in the U.S. suffer from diabetes at much higher rates – 23% versus 12% – and this often occurs even in the absence of obesity.”

Dr. Khera noted that the 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease identify South Asian ancestry as a risk-enhancing factor, calling this a “stopgap measure.” More work is needed, he said, in the research arena and in the clinic.
 

Zero South Asians included in studies used to develop risk estimator

“I think the first step is to simply acknowledge that the risk estimators we use in clinical practice have important limitations when it comes to diverse patient populations,” Dr. Khera said in an interview. “We saw this in our study, where – despite a more than doubling of risk – the predicted risk based on the equations used in primary care showed no difference. This risk estimator was developed based on legacy cohort studies, in [which] zero South Asians were included. Despite important differences across race/ethnicity, the current state-of-the-art in the U.S. is to use one equation for Black individuals and another for all other ethnicities.”

Experts suggest steps for reducing heart disease risk

While risk modeling remains suboptimal, Dr. Khera suggested that clinicians can take immediate steps to reduce the risk of heart disease among individuals with South Asian ancestry.

“Despite all of the uncertainty – we still don’t have a complete understanding of why the risk is so high – there are still several things primary care doctors can do for their patients,” Dr. Khera said.

Foremost, he recommended lifestyle and dietary counseling.

“Dietary counseling is particularly effective if put in the context of cultural norms,” Dr. Khera said. “Many South Asians consider fruit juices or white rice to be healthy, when they lead to rapid spikes in blood sugar.”

Dr. Khera also advised earlier heart disease screening, such as coronary calcium scanning “sometime between age 40-50 years,” noting that positive test results may motivate patients to start or adhere to medications, such as cholesterol-lowering therapies. If necessary, clinicians can also refer to heart centers for South Asian patients, which are becoming increasingly common.

According to Cheryl A.M. Anderson, PhD, chair of the AHA’s Council on Epidemiology and Prevention, and professor and dean of the Herbert Wertheim School of Public Health and Human Longevity Science at the University of California, San Diego, the current study suggests that heart disease management strategies for South Asian patients may be lacking.

“We have had a tradition of preventing or trying to treat heart disease in a fashion that doesn’t yet account for the increased risk that might be prevalent in those of South Asian ancestry,” Dr. Anderson said in an interview.

She suggested that improving associated risk-analysis tools could be beneficial, although the tools themselves, in the context of race or ethnicity, may present their own risks.

“We want to be mindful of potential adverse implications from having everything linked to one’s ancestry, which I think this tool doesn’t do,” Dr. Anderson said, referring to the AHA/ACC Pooled Cohort Equations. “But in sort of the bigger picture of things, we always want to expand and refine our toolkit.”

According to Rajesh Dash, MD, PhD, associate professor, cardiologist, and director of the South Asian Translational Heart Initiative (SSATHI) Prevention Clinic and CardioClick Telemedicine Clinic at Stanford (Calif.) HealthCare, the science supports more active risk mitigation strategies for South Asian patients, and the AHA and the ACC “are the two entities that need to lead the way.”

“Certainly the American Heart Association and the American College of Cardiology should be taking a more active leadership role in this,” Dr. Dash said in an interview.

In 2018, the AHA issued a scientific statement about the elevated risk of ASCVD among South Asian individuals, “but it did not rise to the level of specific recommendations, and did not necessarily go as far as to incorporate new screening parameters for that population,” Dr. Dash said. He also noted that the most recent AHA/ACC guideline identifies South Asian ancestry as a risk-enhancing feature, a statement similarly lacking in actionable value.

“That does not definitively lead someone like a primary care physician to a decision to start a statin, or to be more aggressive with a diagnostic workup, like a stress test, for instance, for a patient who they otherwise would not have done one in had they not been South Asian,” Dr. Dash said.

The steps taken by the AHA and the ACC are “a healthy step forward,” he noted, “but not nearly the degree of attention or vigilance that is required, as well as the level of action that is required to change the narrative for the population.”

At the SSATHI Prevention Clinic, Dr. Dash and colleagues aren’t waiting for the narrative to change, and are already taking a more aggressive approach.

The clinic has an average patient age of 41 years, “easily 15 years younger than the average age in most cardiology clinics,” Dr. Dash said, based on the fact that approximately two-thirds of heart attacks in South Asian individuals occur under the age of 55. “We have to look earlier.”

The SSATHI Prevention Clinic screens for both traditional and emerging risk factors, and Dr. Dash suggested that primary care doctors should do the same.

“If you have a South Asian patient as a primary care physician, you should be aggressively looking for risk factors, traditional ones to start, like elevated cholesterol, hypertension, diabetes, or – and I would argue strongly – prediabetes or insulin resistance.”

Dr. Dash also recommended looking into family history, and considering screening for inflammatory biomarkers, the latter of which are commonly elevated at an earlier age among South Asian individuals, and may have a relatively greater prognostic impact.

To encourage broader implementation of this kind of approach, Dr. Dash called for more large-scale studies. Ideally, these would be randomized clinical trials, but, realistically, real-world datasets may be the answer.

The study was supported by the National Heart, Lung, and Blood Institute; the Broad Institute at MIT and Harvard; the National Human Genome Research Institute; and others. The investigators disclosed relationships with IBM Research, Sanofi, Amgen, and others. Dr. Dash disclosed relationships with HealthPals and AstraZeneca. Dr. Anderson reported no relevant conflicts of interest.

Support for a cardiovascular benefit of omega-3 fatty acids, particularly eicosapentaenoic acid (EPA), has come from a new systematic review and meta-analysis of randomized trials.

The meta-analysis of 38 randomized controlled trials found that omega-3 fatty acids improved cardiovascular outcomes, with a greater reduction in cardiovascular risk in studies of EPA alone rather than of combined eicosapentaenoic plus docosahexaenoic acid (DHA) supplements.

The paper was published online in EClinicalMedicine.

Senior author Deepak Bhatt, MD, Brigham and Women’s Hospital, Boston, was also lead investigator of the REDUCE-IT trial, which is included in the analysis and showed a 25% relative risk reduction in major cardiovascular events with a high-dose EPA product.

But the REDUCE-IT trial has been mired in controversy, with suggestions that the benefit seen might have been exaggerated because of the use of a harmful placebo. In addition, a second large trial of high-dose omega-3 fatty acids, STRENGTH (which tested a combination EPA/DHA product) showed no benefit on cardiovascular outcomes.

Dr. Bhatt said the new meta-analysis provides “a totality of evidence” that “supports a robust and consistent benefit of EPA.”

In the review, the authors concluded: “In this systematic review and meta-analysis, we noted moderate certainty of evidence favoring omega-3 fatty acids for reducing cardiovascular mortality and outcomes. ... The magnitude of relative reductions was robust in EPA trials versus those of EPA+DHA, suggesting differential effects of EPA and DHA in cardiovascular risk reduction.”
 

Controversy continues

But commenting on the publication for an interview, Steven Nissen, MD, Cleveland Clinic, who led the STRENGTH trial, pointed out that 85% of the EPA data in the new meta-analysis came from REDUCE-IT, so the results were a “foregone conclusion.”

“The purpose of a meta-analysis is to answer scientific questions when existing studies are too small to yield statistically robust results. That is not the case here,” Dr. Nissen stated.

He added: “There are only two major trials of EPA and both have important flaws. REDUCE-IT used a questionable placebo (mineral oil) and JELIS was an open-label trial that studied patients with baseline LDL [cholesterol] of 180 mg/dL that was not appropriately treated. A meta-analysis is only as good as the studies that it includes. The other EPA plus DHA studies were essentially neutral.”

Dr. Bhatt responded that, “to date, every randomized trial of EPA only has been positive. Some have been placebo controlled, some have been open label. This meta-analysis corroborates the results of each of those trials in a statistically robust way.”

He added: “Of course, REDUCE-IT is the most rigorous, contemporary trial of EPA. However, in our meta-analysis, even when excluding REDUCE-IT (or for that matter, JELIS), the EPA trials still significantly reduced cardiovascular events.”

Dr. Bhatt also pointed out that two randomized imaging studies, CHERRY and EVAPORATE, have shown benefits of EPA.

“Beyond the clinical trial data, there is a growing amount of evidence supporting the unique biological actions of different omega-3 fatty acids. EPA, in particular, appears to have the strongest basic science evidence supporting cardiovascular benefits. Overall, it is a remarkably consistent scientific story in support of EPA’s beneficial effects on cardiovascular health,” he stated.
 

38 trials included

For the current paper, Dr. Bhatt and coauthors performed a comprehensive literature search for randomized trials comparing omega-3 fatty acids with control (placebo, no supplementation, or lower dose of omega-3 fatty acids) in adults, with a follow-up of at least 12 months, and mortality and cardiovascular outcomes as endpoints.

Ultimately, 38 trials encompassing 149,051 patients were included. Of these, four trials compared EPA with control, 34 trials compared EPA+DHA with control, and 22 trials were in primary prevention. The dose of omega-3 fatty acids ranged from 0.4 g/day to 5.5 g/day.

A total of 25 trials with 143,514 individuals reported 5,550 events of cardiovascular mortality, and 24 trials with 140,983 individuals reported 10,795 events of all-cause mortality.

Omega-3 fatty acids were associated with reduced cardiovascular mortality (rate ratio, 0.93; P = .01), but not all-cause mortality (RR, 0.97; P = .27). The meta-analysis showed reduction in cardiovascular mortality with EPA monotherapy (RR, 0.82; P = .04) and EPA+DHA combination (RR, 0.94; P = .02).

A total of 20 trials with 125,611 individuals reported 2,989 nonfatal myocardial infarction events, and 29 trials with 144,384 individuals reported 9,153 coronary heart disease (CHD) events.

Omega-3 fatty acids were associated with reducing nonfatal MI (RR, 0.87; P = .0001) and CHD (RR, 0.91; P = .0002). The meta-analysis showed higher risk reductions in nonfatal MI with EPA monotherapy (RR, 0.72; P = .00002) than with EPA+DHA combination (RR, 0.92; P = .05), and also for CHD events with EPA monotherapy (RR, 0.73; P = .00004) than with EPA+DHA combination (RR, 0.94; P = .01).

A total of 17 trials (n = 135,019) reported 13,234 events of MACE, and 13 trials (n = 117,890) reported 7,416 events of revascularization.

Omega-3 fatty acids were associated with reducing MACE (RR, 0.95; P = .002) and revascularization (RR, 0.91; P = .0001). The meta-analysis showed higher risk reductions in MACE with EPA monotherapy (RR, 0.78; P = .00000001), whereas EPA+DHA combination did not reduce MACE (RR, 0.99; P = .48). This effect was consistent for revascularization.

A total of eight trials with 65,404 individuals reported 935 nonfatal strokes, and eight trials with 51,336 individuals reported 1,572 events of atrial fibrillation (AFib).

Omega-3 fatty acids did not significantly reduce nonfatal stroke (RR, 1.04; P = .55), but EPA monotherapy was associated with a reduction of nonfatal stroke, compared with control (RR: 0.71; P = .01).

Conversely, omega-3 fatty acids were associated with increased risk for AFib (RR, 1.26; P = .004), with a higher risk with EPA monotherapy than with control (RR, 1.35; P = .004).

Overall, omega-3 fatty acids did not prevent sudden cardiac death or increase gastrointestinal-related adverse events, total bleeding, or major or minor bleeding; however, the meta-analysis showed a higher risk of total bleeding with EPA monotherapy than with control (RR, 1.49; P = .006).

An influence analysis with stepwise exclusion of one trial at a time, including REDUCE-IT, did not alter the overall summary estimates. “Despite the exclusion of REDUCE-IT, EPA monotherapy reduced MACE by 23%, compared with the control,” the authors reported.

They said these new findings also have important implications for clinical practice and treatment guidelines.

“After REDUCE-IT, several national and international guidelines endorsed EPA in their therapeutic recommendations. However, the publication of two recent negative trials of EPA + DHA has created some confusion in the scientific community about the value of omega-3 FAs in preventing atherosclerotic cardiovascular disease [ASCVD],” they stated.

“This meta-analysis provides reassurance about the role of omega-3 fatty acids, specifically EPA, in the current treatment framework of ASCVD residual cardiovascular risk reduction and encourages investigators to explore further the cardiovascular effects of EPA across different clinical settings,” they added.

REDUCE-IT was sponsored by Amarin. Brigham and Women’s Hospital receives research funding from Amarin for the work Dr. Bhatt did as the trial chair and as the international principal investigator. The present analysis was unfunded.

A version of this article first appeared on Medscape.com.

Support for a cardiovascular benefit of omega-3 fatty acids, particularly eicosapentaenoic acid (EPA), has come from a new systematic review and meta-analysis of randomized trials.

The meta-analysis of 38 randomized controlled trials found that omega-3 fatty acids improved cardiovascular outcomes, with a greater reduction in cardiovascular risk in studies of EPA alone rather than of combined eicosapentaenoic plus docosahexaenoic acid (DHA) supplements.

The paper was published online in EClinicalMedicine.

Senior author Deepak Bhatt, MD, Brigham and Women’s Hospital, Boston, was also lead investigator of the REDUCE-IT trial, which is included in the analysis and showed a 25% relative risk reduction in major cardiovascular events with a high-dose EPA product.

But the REDUCE-IT trial has been mired in controversy, with suggestions that the benefit seen might have been exaggerated because of the use of a harmful placebo. In addition, a second large trial of high-dose omega-3 fatty acids, STRENGTH (which tested a combination EPA/DHA product) showed no benefit on cardiovascular outcomes.

Dr. Bhatt said the new meta-analysis provides “a totality of evidence” that “supports a robust and consistent benefit of EPA.”

In the review, the authors concluded: “In this systematic review and meta-analysis, we noted moderate certainty of evidence favoring omega-3 fatty acids for reducing cardiovascular mortality and outcomes. ... The magnitude of relative reductions was robust in EPA trials versus those of EPA+DHA, suggesting differential effects of EPA and DHA in cardiovascular risk reduction.”
 

Controversy continues

But commenting on the publication for an interview, Steven Nissen, MD, Cleveland Clinic, who led the STRENGTH trial, pointed out that 85% of the EPA data in the new meta-analysis came from REDUCE-IT, so the results were a “foregone conclusion.”

“The purpose of a meta-analysis is to answer scientific questions when existing studies are too small to yield statistically robust results. That is not the case here,” Dr. Nissen stated.

He added: “There are only two major trials of EPA and both have important flaws. REDUCE-IT used a questionable placebo (mineral oil) and JELIS was an open-label trial that studied patients with baseline LDL [cholesterol] of 180 mg/dL that was not appropriately treated. A meta-analysis is only as good as the studies that it includes. The other EPA plus DHA studies were essentially neutral.”

Dr. Bhatt responded that, “to date, every randomized trial of EPA only has been positive. Some have been placebo controlled, some have been open label. This meta-analysis corroborates the results of each of those trials in a statistically robust way.”

He added: “Of course, REDUCE-IT is the most rigorous, contemporary trial of EPA. However, in our meta-analysis, even when excluding REDUCE-IT (or for that matter, JELIS), the EPA trials still significantly reduced cardiovascular events.”

Dr. Bhatt also pointed out that two randomized imaging studies, CHERRY and EVAPORATE, have shown benefits of EPA.

“Beyond the clinical trial data, there is a growing amount of evidence supporting the unique biological actions of different omega-3 fatty acids. EPA, in particular, appears to have the strongest basic science evidence supporting cardiovascular benefits. Overall, it is a remarkably consistent scientific story in support of EPA’s beneficial effects on cardiovascular health,” he stated.
 

38 trials included

For the current paper, Dr. Bhatt and coauthors performed a comprehensive literature search for randomized trials comparing omega-3 fatty acids with control (placebo, no supplementation, or lower dose of omega-3 fatty acids) in adults, with a follow-up of at least 12 months, and mortality and cardiovascular outcomes as endpoints.

Ultimately, 38 trials encompassing 149,051 patients were included. Of these, four trials compared EPA with control, 34 trials compared EPA+DHA with control, and 22 trials were in primary prevention. The dose of omega-3 fatty acids ranged from 0.4 g/day to 5.5 g/day.

A total of 25 trials with 143,514 individuals reported 5,550 events of cardiovascular mortality, and 24 trials with 140,983 individuals reported 10,795 events of all-cause mortality.

Omega-3 fatty acids were associated with reduced cardiovascular mortality (rate ratio, 0.93; P = .01), but not all-cause mortality (RR, 0.97; P = .27). The meta-analysis showed reduction in cardiovascular mortality with EPA monotherapy (RR, 0.82; P = .04) and EPA+DHA combination (RR, 0.94; P = .02).

A total of 20 trials with 125,611 individuals reported 2,989 nonfatal myocardial infarction events, and 29 trials with 144,384 individuals reported 9,153 coronary heart disease (CHD) events.

Omega-3 fatty acids were associated with reducing nonfatal MI (RR, 0.87; P = .0001) and CHD (RR, 0.91; P = .0002). The meta-analysis showed higher risk reductions in nonfatal MI with EPA monotherapy (RR, 0.72; P = .00002) than with EPA+DHA combination (RR, 0.92; P = .05), and also for CHD events with EPA monotherapy (RR, 0.73; P = .00004) than with EPA+DHA combination (RR, 0.94; P = .01).

A total of 17 trials (n = 135,019) reported 13,234 events of MACE, and 13 trials (n = 117,890) reported 7,416 events of revascularization.

Omega-3 fatty acids were associated with reducing MACE (RR, 0.95; P = .002) and revascularization (RR, 0.91; P = .0001). The meta-analysis showed higher risk reductions in MACE with EPA monotherapy (RR, 0.78; P = .00000001), whereas EPA+DHA combination did not reduce MACE (RR, 0.99; P = .48). This effect was consistent for revascularization.

A total of eight trials with 65,404 individuals reported 935 nonfatal strokes, and eight trials with 51,336 individuals reported 1,572 events of atrial fibrillation (AFib).

Omega-3 fatty acids did not significantly reduce nonfatal stroke (RR, 1.04; P = .55), but EPA monotherapy was associated with a reduction of nonfatal stroke, compared with control (RR: 0.71; P = .01).

Conversely, omega-3 fatty acids were associated with increased risk for AFib (RR, 1.26; P = .004), with a higher risk with EPA monotherapy than with control (RR, 1.35; P = .004).

Overall, omega-3 fatty acids did not prevent sudden cardiac death or increase gastrointestinal-related adverse events, total bleeding, or major or minor bleeding; however, the meta-analysis showed a higher risk of total bleeding with EPA monotherapy than with control (RR, 1.49; P = .006).

An influence analysis with stepwise exclusion of one trial at a time, including REDUCE-IT, did not alter the overall summary estimates. “Despite the exclusion of REDUCE-IT, EPA monotherapy reduced MACE by 23%, compared with the control,” the authors reported.

They said these new findings also have important implications for clinical practice and treatment guidelines.

“After REDUCE-IT, several national and international guidelines endorsed EPA in their therapeutic recommendations. However, the publication of two recent negative trials of EPA + DHA has created some confusion in the scientific community about the value of omega-3 FAs in preventing atherosclerotic cardiovascular disease [ASCVD],” they stated.

“This meta-analysis provides reassurance about the role of omega-3 fatty acids, specifically EPA, in the current treatment framework of ASCVD residual cardiovascular risk reduction and encourages investigators to explore further the cardiovascular effects of EPA across different clinical settings,” they added.

REDUCE-IT was sponsored by Amarin. Brigham and Women’s Hospital receives research funding from Amarin for the work Dr. Bhatt did as the trial chair and as the international principal investigator. The present analysis was unfunded.

A version of this article first appeared on Medscape.com.

Support for a cardiovascular benefit of omega-3 fatty acids, particularly eicosapentaenoic acid (EPA), has come from a new systematic review and meta-analysis of randomized trials.

The meta-analysis of 38 randomized controlled trials found that omega-3 fatty acids improved cardiovascular outcomes, with a greater reduction in cardiovascular risk in studies of EPA alone rather than of combined eicosapentaenoic plus docosahexaenoic acid (DHA) supplements.

The paper was published online in EClinicalMedicine.

Senior author Deepak Bhatt, MD, Brigham and Women’s Hospital, Boston, was also lead investigator of the REDUCE-IT trial, which is included in the analysis and showed a 25% relative risk reduction in major cardiovascular events with a high-dose EPA product.

But the REDUCE-IT trial has been mired in controversy, with suggestions that the benefit seen might have been exaggerated because of the use of a harmful placebo. In addition, a second large trial of high-dose omega-3 fatty acids, STRENGTH (which tested a combination EPA/DHA product) showed no benefit on cardiovascular outcomes.

Dr. Bhatt said the new meta-analysis provides “a totality of evidence” that “supports a robust and consistent benefit of EPA.”

In the review, the authors concluded: “In this systematic review and meta-analysis, we noted moderate certainty of evidence favoring omega-3 fatty acids for reducing cardiovascular mortality and outcomes. ... The magnitude of relative reductions was robust in EPA trials versus those of EPA+DHA, suggesting differential effects of EPA and DHA in cardiovascular risk reduction.”
 

Controversy continues

But commenting on the publication for an interview, Steven Nissen, MD, Cleveland Clinic, who led the STRENGTH trial, pointed out that 85% of the EPA data in the new meta-analysis came from REDUCE-IT, so the results were a “foregone conclusion.”

“The purpose of a meta-analysis is to answer scientific questions when existing studies are too small to yield statistically robust results. That is not the case here,” Dr. Nissen stated.

He added: “There are only two major trials of EPA and both have important flaws. REDUCE-IT used a questionable placebo (mineral oil) and JELIS was an open-label trial that studied patients with baseline LDL [cholesterol] of 180 mg/dL that was not appropriately treated. A meta-analysis is only as good as the studies that it includes. The other EPA plus DHA studies were essentially neutral.”

Dr. Bhatt responded that, “to date, every randomized trial of EPA only has been positive. Some have been placebo controlled, some have been open label. This meta-analysis corroborates the results of each of those trials in a statistically robust way.”

He added: “Of course, REDUCE-IT is the most rigorous, contemporary trial of EPA. However, in our meta-analysis, even when excluding REDUCE-IT (or for that matter, JELIS), the EPA trials still significantly reduced cardiovascular events.”

Dr. Bhatt also pointed out that two randomized imaging studies, CHERRY and EVAPORATE, have shown benefits of EPA.

“Beyond the clinical trial data, there is a growing amount of evidence supporting the unique biological actions of different omega-3 fatty acids. EPA, in particular, appears to have the strongest basic science evidence supporting cardiovascular benefits. Overall, it is a remarkably consistent scientific story in support of EPA’s beneficial effects on cardiovascular health,” he stated.
 

38 trials included

For the current paper, Dr. Bhatt and coauthors performed a comprehensive literature search for randomized trials comparing omega-3 fatty acids with control (placebo, no supplementation, or lower dose of omega-3 fatty acids) in adults, with a follow-up of at least 12 months, and mortality and cardiovascular outcomes as endpoints.

Ultimately, 38 trials encompassing 149,051 patients were included. Of these, four trials compared EPA with control, 34 trials compared EPA+DHA with control, and 22 trials were in primary prevention. The dose of omega-3 fatty acids ranged from 0.4 g/day to 5.5 g/day.

A total of 25 trials with 143,514 individuals reported 5,550 events of cardiovascular mortality, and 24 trials with 140,983 individuals reported 10,795 events of all-cause mortality.

Omega-3 fatty acids were associated with reduced cardiovascular mortality (rate ratio, 0.93; P = .01), but not all-cause mortality (RR, 0.97; P = .27). The meta-analysis showed reduction in cardiovascular mortality with EPA monotherapy (RR, 0.82; P = .04) and EPA+DHA combination (RR, 0.94; P = .02).

A total of 20 trials with 125,611 individuals reported 2,989 nonfatal myocardial infarction events, and 29 trials with 144,384 individuals reported 9,153 coronary heart disease (CHD) events.

Omega-3 fatty acids were associated with reducing nonfatal MI (RR, 0.87; P = .0001) and CHD (RR, 0.91; P = .0002). The meta-analysis showed higher risk reductions in nonfatal MI with EPA monotherapy (RR, 0.72; P = .00002) than with EPA+DHA combination (RR, 0.92; P = .05), and also for CHD events with EPA monotherapy (RR, 0.73; P = .00004) than with EPA+DHA combination (RR, 0.94; P = .01).

A total of 17 trials (n = 135,019) reported 13,234 events of MACE, and 13 trials (n = 117,890) reported 7,416 events of revascularization.

Omega-3 fatty acids were associated with reducing MACE (RR, 0.95; P = .002) and revascularization (RR, 0.91; P = .0001). The meta-analysis showed higher risk reductions in MACE with EPA monotherapy (RR, 0.78; P = .00000001), whereas EPA+DHA combination did not reduce MACE (RR, 0.99; P = .48). This effect was consistent for revascularization.

A total of eight trials with 65,404 individuals reported 935 nonfatal strokes, and eight trials with 51,336 individuals reported 1,572 events of atrial fibrillation (AFib).

Omega-3 fatty acids did not significantly reduce nonfatal stroke (RR, 1.04; P = .55), but EPA monotherapy was associated with a reduction of nonfatal stroke, compared with control (RR: 0.71; P = .01).

Conversely, omega-3 fatty acids were associated with increased risk for AFib (RR, 1.26; P = .004), with a higher risk with EPA monotherapy than with control (RR, 1.35; P = .004).

Overall, omega-3 fatty acids did not prevent sudden cardiac death or increase gastrointestinal-related adverse events, total bleeding, or major or minor bleeding; however, the meta-analysis showed a higher risk of total bleeding with EPA monotherapy than with control (RR, 1.49; P = .006).

An influence analysis with stepwise exclusion of one trial at a time, including REDUCE-IT, did not alter the overall summary estimates. “Despite the exclusion of REDUCE-IT, EPA monotherapy reduced MACE by 23%, compared with the control,” the authors reported.

They said these new findings also have important implications for clinical practice and treatment guidelines.

“After REDUCE-IT, several national and international guidelines endorsed EPA in their therapeutic recommendations. However, the publication of two recent negative trials of EPA + DHA has created some confusion in the scientific community about the value of omega-3 FAs in preventing atherosclerotic cardiovascular disease [ASCVD],” they stated.

“This meta-analysis provides reassurance about the role of omega-3 fatty acids, specifically EPA, in the current treatment framework of ASCVD residual cardiovascular risk reduction and encourages investigators to explore further the cardiovascular effects of EPA across different clinical settings,” they added.

REDUCE-IT was sponsored by Amarin. Brigham and Women’s Hospital receives research funding from Amarin for the work Dr. Bhatt did as the trial chair and as the international principal investigator. The present analysis was unfunded.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration approved finerenone (Kerendia), the first agent from a new class of nonsteroidal mineralocorticoid receptor antagonists (MRAs), on July 9 for treating patients with chronic kidney disease (CKD) associated with type 2 diabetes.

Janani Rangaswami, MD, a nephrologist not involved with finerenone’s development, hailed the action as a “welcome addition to therapies in the cardiorenal space.”

She also highlighted that until more evidence accumulates, finerenone will take a back seat to two more established renal-protective drug classes for patients with type 2 diabetes, the renin-angiotensin system inhibitors (RASIs), and the sodium-glucose cotransporter 2 (SGLT2) inhibitors.

RASIs, which include angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, remain first-line treatments for slowing the progression of CKD in patients with type 2 diabetes. The efficacy and safety of these agents are well-established. The trial that led to the FDA’s decision to approve finerenone, FIDELIO-DKD, compared it against placebo in more than 5,700 patients with type 2 diabetes who were all already taking a maximum-tolerated dose of an RASI.
 

Scant data on combining finerenone with an SGLT2 inhibitor

Two agents in the SGLT2 inhibitor class, approved initially for type 2 diabetes, received additional FDA approvals for slowing kidney disease: Canagliflozin (Invokana), which was approved in September 2019 on the basis of the CREDENCE trial, and dapagliflozin (Forxiga/Farxiga), which was approved in April 2021 on the basis of DAPA-CKD. Nephrologists now speak of this drug class as “practice changing.”

When FIDELIO-DKD enrolled patients from September 2015 to June 2018, it was still early days for use of SGLT2 inhibitors for patients with type 2 diabetes; hence, fewer than 5% of enrolled patients received an SGLT2 inhibitor, making it impossible to say how well finerenone works when taken along with one of these drugs.

“The big question that persists is the incremental benefit [from finerenone] on top of an SGLT2 inhibitor,” commented Dr. Rangaswami, director of the cardiorenal program at George Washington University, Washington, and chair-elect of the Council on the Kidney in Cardiovascular Disease of the American Heart Association.

“It is hard to extrapolate incremental benefit from existing finerenone trial data given the low background use of SGLT2 inhibitors [in FIDELIO-DKD],” she said in an interview.

George Bakris, MD, lead investigator for FIDELIO-DKD, agrees.
 

SGLT2 inhibitors are a ‘must’ for CKD

An SGLT2 inhibitor “must be used, period,” for patients with type 2 diabetes and CKD. “The evidence is very strong,” said Dr. Bakris, speaking in June 2021 during a session of the virtual annual Congress of the European Renal Association and European Dialysis and Transplant Association.

Because of inadequate evidence on how finerenone works when administered in addition to an SGLT2 inhibitor, for the time being, the combination must be considered investigational, he added.

Study results “need to show that combination therapy [with an SGLT2 inhibitor and finerenone] is better” than an SGLT2 inhibitor alone, said Dr. Bakris, professor of medicine and director of the Comprehensive Hypertension Center of the University of Chicago.

During his June talk, Dr. Bakris predicted that by 2023, enough data will exist from patients treated with both an SGLT2 inhibitor and finerenone to allow an evidence-based approach to combination treatment.

Finerenone’s approval makes it an immediate choice for patients with type 2 diabetes and CKD secondary to polycystic kidney disease, a group who are not candidates for an SGLT2 inhibitor, said Dr. Rangaswami.

But “if a patient is eligible for an SGLT2 inhibitor, I would not stop that in favor of starting finerenone” on the basis of current knowledge, she noted.
 

‘Not your mother’s spironolactone’

Although finerenone is classified an MRA, the class that also includes the steroidal agents spironolactone and eplerenone, the nonsteroidal structure of finerenone means “it has nothing to do with spironolactone. It’s a different molecule with different chemistry,” Dr. Bakris said in his June talk.

Although the risk for hyperkalemia has been a limiting factor and a deterrent to routine use of steroidal MRAs for preventing progression of CKD, hyperkalemia is much less of a problem with finerenone.

Main results from FIDELIO-DKD, published in late 2020, showed that the percentage of patients receiving finerenone who permanently stopped taking the drug because of hyperkalemia was 2.3%, higher than the 0.9% rate among patients in the trial who received placebo but about a third of the rate of patients treated with spironolactone in a historical cohort.

“You need to pay attention” to the potential development of hyperkalemia in patients taking finerenone, “but it is not a major issue,” Dr. Bakris said. “Finerenone is not your mother’s spironolactone,” he declared.

FIDELIO-DKD’s primary outcome, a combination of several adverse renal events, showed that treatment with finerenone cut this endpoint by a significant 18% compared with placebo. The study’s main secondary endpoint showed that finerenone cut the incidence of combined cardiovascular disease events by a significant 14% compared with placebo. Adverse events were similar in the finerenone and placebo arms.
 

Finerenone also shows promise for reducing CVD events

Bayer, the company that developed and will market finerenone, announced in May 2021 topline results from a companion trial, FIGARO-DKD. That trial also enrolled patients with type 2 diabetes and CKD, but a primary endpoint of that trial combined the rates of cardiovascular death and nonfatal cardiovascular disease events. The results from this trial showed a significant difference in favor of finerenone compared with placebo.

“Given the common pathways that progression of CKD and cardiovascular disease share with respect to [moderating] inflammation and [slowing development of] fibrosis, it is not surprising that a signal for benefit was seen at the different ends of the cardiorenal spectrum,” Dr. Rangaswami said.

FIDELIO-DKD and FIGARO-DKD were sponsored by Bayer, the company that markets finerenone (Kerendia). Dr. Bakris has been a consultant to and has received research funding from Bayer and from numerous other companies. Dr. Rangaswami has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration approved finerenone (Kerendia), the first agent from a new class of nonsteroidal mineralocorticoid receptor antagonists (MRAs), on July 9 for treating patients with chronic kidney disease (CKD) associated with type 2 diabetes.

Janani Rangaswami, MD, a nephrologist not involved with finerenone’s development, hailed the action as a “welcome addition to therapies in the cardiorenal space.”

She also highlighted that until more evidence accumulates, finerenone will take a back seat to two more established renal-protective drug classes for patients with type 2 diabetes, the renin-angiotensin system inhibitors (RASIs), and the sodium-glucose cotransporter 2 (SGLT2) inhibitors.

RASIs, which include angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, remain first-line treatments for slowing the progression of CKD in patients with type 2 diabetes. The efficacy and safety of these agents are well-established. The trial that led to the FDA’s decision to approve finerenone, FIDELIO-DKD, compared it against placebo in more than 5,700 patients with type 2 diabetes who were all already taking a maximum-tolerated dose of an RASI.
 

Scant data on combining finerenone with an SGLT2 inhibitor

Two agents in the SGLT2 inhibitor class, approved initially for type 2 diabetes, received additional FDA approvals for slowing kidney disease: Canagliflozin (Invokana), which was approved in September 2019 on the basis of the CREDENCE trial, and dapagliflozin (Forxiga/Farxiga), which was approved in April 2021 on the basis of DAPA-CKD. Nephrologists now speak of this drug class as “practice changing.”

When FIDELIO-DKD enrolled patients from September 2015 to June 2018, it was still early days for use of SGLT2 inhibitors for patients with type 2 diabetes; hence, fewer than 5% of enrolled patients received an SGLT2 inhibitor, making it impossible to say how well finerenone works when taken along with one of these drugs.

“The big question that persists is the incremental benefit [from finerenone] on top of an SGLT2 inhibitor,” commented Dr. Rangaswami, director of the cardiorenal program at George Washington University, Washington, and chair-elect of the Council on the Kidney in Cardiovascular Disease of the American Heart Association.

“It is hard to extrapolate incremental benefit from existing finerenone trial data given the low background use of SGLT2 inhibitors [in FIDELIO-DKD],” she said in an interview.

George Bakris, MD, lead investigator for FIDELIO-DKD, agrees.
 

SGLT2 inhibitors are a ‘must’ for CKD

An SGLT2 inhibitor “must be used, period,” for patients with type 2 diabetes and CKD. “The evidence is very strong,” said Dr. Bakris, speaking in June 2021 during a session of the virtual annual Congress of the European Renal Association and European Dialysis and Transplant Association.

Because of inadequate evidence on how finerenone works when administered in addition to an SGLT2 inhibitor, for the time being, the combination must be considered investigational, he added.

Study results “need to show that combination therapy [with an SGLT2 inhibitor and finerenone] is better” than an SGLT2 inhibitor alone, said Dr. Bakris, professor of medicine and director of the Comprehensive Hypertension Center of the University of Chicago.

During his June talk, Dr. Bakris predicted that by 2023, enough data will exist from patients treated with both an SGLT2 inhibitor and finerenone to allow an evidence-based approach to combination treatment.

Finerenone’s approval makes it an immediate choice for patients with type 2 diabetes and CKD secondary to polycystic kidney disease, a group who are not candidates for an SGLT2 inhibitor, said Dr. Rangaswami.

But “if a patient is eligible for an SGLT2 inhibitor, I would not stop that in favor of starting finerenone” on the basis of current knowledge, she noted.
 

‘Not your mother’s spironolactone’

Although finerenone is classified an MRA, the class that also includes the steroidal agents spironolactone and eplerenone, the nonsteroidal structure of finerenone means “it has nothing to do with spironolactone. It’s a different molecule with different chemistry,” Dr. Bakris said in his June talk.

Although the risk for hyperkalemia has been a limiting factor and a deterrent to routine use of steroidal MRAs for preventing progression of CKD, hyperkalemia is much less of a problem with finerenone.

Main results from FIDELIO-DKD, published in late 2020, showed that the percentage of patients receiving finerenone who permanently stopped taking the drug because of hyperkalemia was 2.3%, higher than the 0.9% rate among patients in the trial who received placebo but about a third of the rate of patients treated with spironolactone in a historical cohort.

“You need to pay attention” to the potential development of hyperkalemia in patients taking finerenone, “but it is not a major issue,” Dr. Bakris said. “Finerenone is not your mother’s spironolactone,” he declared.

FIDELIO-DKD’s primary outcome, a combination of several adverse renal events, showed that treatment with finerenone cut this endpoint by a significant 18% compared with placebo. The study’s main secondary endpoint showed that finerenone cut the incidence of combined cardiovascular disease events by a significant 14% compared with placebo. Adverse events were similar in the finerenone and placebo arms.
 

Finerenone also shows promise for reducing CVD events

Bayer, the company that developed and will market finerenone, announced in May 2021 topline results from a companion trial, FIGARO-DKD. That trial also enrolled patients with type 2 diabetes and CKD, but a primary endpoint of that trial combined the rates of cardiovascular death and nonfatal cardiovascular disease events. The results from this trial showed a significant difference in favor of finerenone compared with placebo.

“Given the common pathways that progression of CKD and cardiovascular disease share with respect to [moderating] inflammation and [slowing development of] fibrosis, it is not surprising that a signal for benefit was seen at the different ends of the cardiorenal spectrum,” Dr. Rangaswami said.

FIDELIO-DKD and FIGARO-DKD were sponsored by Bayer, the company that markets finerenone (Kerendia). Dr. Bakris has been a consultant to and has received research funding from Bayer and from numerous other companies. Dr. Rangaswami has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration approved finerenone (Kerendia), the first agent from a new class of nonsteroidal mineralocorticoid receptor antagonists (MRAs), on July 9 for treating patients with chronic kidney disease (CKD) associated with type 2 diabetes.

Janani Rangaswami, MD, a nephrologist not involved with finerenone’s development, hailed the action as a “welcome addition to therapies in the cardiorenal space.”

She also highlighted that until more evidence accumulates, finerenone will take a back seat to two more established renal-protective drug classes for patients with type 2 diabetes, the renin-angiotensin system inhibitors (RASIs), and the sodium-glucose cotransporter 2 (SGLT2) inhibitors.

RASIs, which include angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, remain first-line treatments for slowing the progression of CKD in patients with type 2 diabetes. The efficacy and safety of these agents are well-established. The trial that led to the FDA’s decision to approve finerenone, FIDELIO-DKD, compared it against placebo in more than 5,700 patients with type 2 diabetes who were all already taking a maximum-tolerated dose of an RASI.
 

Scant data on combining finerenone with an SGLT2 inhibitor

Two agents in the SGLT2 inhibitor class, approved initially for type 2 diabetes, received additional FDA approvals for slowing kidney disease: Canagliflozin (Invokana), which was approved in September 2019 on the basis of the CREDENCE trial, and dapagliflozin (Forxiga/Farxiga), which was approved in April 2021 on the basis of DAPA-CKD. Nephrologists now speak of this drug class as “practice changing.”

When FIDELIO-DKD enrolled patients from September 2015 to June 2018, it was still early days for use of SGLT2 inhibitors for patients with type 2 diabetes; hence, fewer than 5% of enrolled patients received an SGLT2 inhibitor, making it impossible to say how well finerenone works when taken along with one of these drugs.

“The big question that persists is the incremental benefit [from finerenone] on top of an SGLT2 inhibitor,” commented Dr. Rangaswami, director of the cardiorenal program at George Washington University, Washington, and chair-elect of the Council on the Kidney in Cardiovascular Disease of the American Heart Association.

“It is hard to extrapolate incremental benefit from existing finerenone trial data given the low background use of SGLT2 inhibitors [in FIDELIO-DKD],” she said in an interview.

George Bakris, MD, lead investigator for FIDELIO-DKD, agrees.
 

SGLT2 inhibitors are a ‘must’ for CKD

An SGLT2 inhibitor “must be used, period,” for patients with type 2 diabetes and CKD. “The evidence is very strong,” said Dr. Bakris, speaking in June 2021 during a session of the virtual annual Congress of the European Renal Association and European Dialysis and Transplant Association.

Because of inadequate evidence on how finerenone works when administered in addition to an SGLT2 inhibitor, for the time being, the combination must be considered investigational, he added.

Study results “need to show that combination therapy [with an SGLT2 inhibitor and finerenone] is better” than an SGLT2 inhibitor alone, said Dr. Bakris, professor of medicine and director of the Comprehensive Hypertension Center of the University of Chicago.

During his June talk, Dr. Bakris predicted that by 2023, enough data will exist from patients treated with both an SGLT2 inhibitor and finerenone to allow an evidence-based approach to combination treatment.

Finerenone’s approval makes it an immediate choice for patients with type 2 diabetes and CKD secondary to polycystic kidney disease, a group who are not candidates for an SGLT2 inhibitor, said Dr. Rangaswami.

But “if a patient is eligible for an SGLT2 inhibitor, I would not stop that in favor of starting finerenone” on the basis of current knowledge, she noted.
 

‘Not your mother’s spironolactone’

Although finerenone is classified an MRA, the class that also includes the steroidal agents spironolactone and eplerenone, the nonsteroidal structure of finerenone means “it has nothing to do with spironolactone. It’s a different molecule with different chemistry,” Dr. Bakris said in his June talk.

Although the risk for hyperkalemia has been a limiting factor and a deterrent to routine use of steroidal MRAs for preventing progression of CKD, hyperkalemia is much less of a problem with finerenone.

Main results from FIDELIO-DKD, published in late 2020, showed that the percentage of patients receiving finerenone who permanently stopped taking the drug because of hyperkalemia was 2.3%, higher than the 0.9% rate among patients in the trial who received placebo but about a third of the rate of patients treated with spironolactone in a historical cohort.

“You need to pay attention” to the potential development of hyperkalemia in patients taking finerenone, “but it is not a major issue,” Dr. Bakris said. “Finerenone is not your mother’s spironolactone,” he declared.

FIDELIO-DKD’s primary outcome, a combination of several adverse renal events, showed that treatment with finerenone cut this endpoint by a significant 18% compared with placebo. The study’s main secondary endpoint showed that finerenone cut the incidence of combined cardiovascular disease events by a significant 14% compared with placebo. Adverse events were similar in the finerenone and placebo arms.
 

Finerenone also shows promise for reducing CVD events

Bayer, the company that developed and will market finerenone, announced in May 2021 topline results from a companion trial, FIGARO-DKD. That trial also enrolled patients with type 2 diabetes and CKD, but a primary endpoint of that trial combined the rates of cardiovascular death and nonfatal cardiovascular disease events. The results from this trial showed a significant difference in favor of finerenone compared with placebo.

“Given the common pathways that progression of CKD and cardiovascular disease share with respect to [moderating] inflammation and [slowing development of] fibrosis, it is not surprising that a signal for benefit was seen at the different ends of the cardiorenal spectrum,” Dr. Rangaswami said.

FIDELIO-DKD and FIGARO-DKD were sponsored by Bayer, the company that markets finerenone (Kerendia). Dr. Bakris has been a consultant to and has received research funding from Bayer and from numerous other companies. Dr. Rangaswami has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Catheter ablation appears better than drug therapy for treating atrial fibrillation (AFib) in racial and ethnic minorities, according to a new look at CABANA trial data.

CABANA, which was undertaken to compare catheter ablation and rate-control or rhythm-control drug therapy for AFib, concluded there was no significant difference between the two strategies in improving the trial’s composite primary outcome of death, disabling stroke, serious bleeding, or cardiac arrest.

But a closer look at a subgroup of participants reveals an important difference in outcome among racial and ethnic minorities.

In that group, which made up about 10% of the CABANA study population, catheter ablation was significantly better at treating AFib than was drug therapy, producing roughly a 70% relative reduction in the primary endpoint and all-cause mortality.

The benefit for catheter ablation, which was not seen in the nonminority participants, appeared to be due to worse outcomes with drug therapy, the investigators report in an article published July 5 in the Journal of the American College of Cardiology.

“The study really highlights the importance of trying to secure an inclusive and diverse population in clinical trials,” lead author Kevin L. Thomas, MD, Duke University, Durham, N.C., said in an interview.

“When we focused on the racial and ethnic minorities who were included in CABANA, the findings were different. This was a surprise,” Dr. Thomas said.

“The findings from the secondary analysis of CABANA suggest that racial and ethnic minorities that are treated with drugs compared with ablation do worse,” he said. “If we can validate this in a larger sample of patients and this does in fact turn out to be true, then we would change how we practice medicine. We would have discussions with these populations about the benefits of ablation over drugs, and this would be important information to help guide our practice.”

The investigators analyzed data from 1,280 participants enrolled in the North American arm of CABANA. Of these, 127 (9.9%) were of racial or ethnic minorities, as defined by the National Institutes of Health, and were randomly assigned to receive ablation (n = 62) or drug therapy (n = 65).

Compared with nonminorities, participants of racial and ethnic minorities were younger (median age, 65.5 years, vs. 68.5 years) and were more likely to have NYHA functional class greater than or equal to II symptoms (37.0% vs. 22.0%), hypertension (92.1% vs. 76.8%), and an ejection fraction less than 40% (20.8% vs. 7.1%).

The overall median follow-up was 54.9 months. Among ethnic and minority participants, the median follow-up was 48 months, compared with 55.5 months for the nonminority participants.

Although there was no significant difference in the primary composite endpoint in the main CABANA trial, among racial and ethnic minorities treated with ablation, there was a 68% relative reduction in the trial’s primary endpoint (adjusted hazard ratio, 0.32; 95% confidence interval, 0.13-0.78) and a 72% relative reduction in all-cause mortality (aHR, 0.28; 95% CI, 0.10-0.79).

The 4-year Kaplan-Meier primary event rates were similar in both racial/ethnic minority and nonminority groups that received catheter ablation (12.3% vs. 9.9%).

However, the 4-year event rate was much higher among nonminority participants than among racial and ethnic minorities who received drug therapy (27.4% vs. 9.4%).

The corresponding all-cause 4-year mortality rates were 8.1% and 6.7%, respectively, in the ablation arm and 20.2% and 4.5%, respectively, in the drug arm.

Dr. Thomas and colleagues point out that heart failure in racial and ethnic minorities, particularly Black patients, is typically due to hypertensive heart disease, whereas in non-Hispanic White patients, it is overwhelmingly associated with coronary artery disease. “Our results in CABANA, therefore, raise the possibility that the variations in the prevalence of the heart diseases associated with AFib might account for differences in the benefits observed with ablation therapy.”

Prior data suggest that AFib in the setting of heart failure with either reduced or preserved ejection fraction has substantially better clinical outcomes with ablation versus drug therapy, but most studies either do not report racial/ethnic demographics or enroll very low numbers of minorities, they note.

Andrea M. Russo, MD, a professor of medicine at Rowan University, Camden, New Jersey, asks why drug therapy might result in worse outcomes in racial and ethnic minorities in an accompanying editorial.

“Those who received ablation did better than those who received drugs, and the main reason for that is not that ablation works better in minorities than nonminorities, it’s because drugs are worse in minority patients than they are in nonminority patients. This means that either the way we are using the drugs or the ones that we are using in minority patients are resulting in worse overall outcomes,” Dr. Russo told this news organization.

“The minority patients were younger and yet had more hypertension at baseline. There could be all kinds of factors contributing to their health,” she said.

Dr. Russo agrees with Dr. Thomas on the need to enroll diverse populations in clinical trials.

“Dr. Thomas should be commended. He did a fabulous job of looking at this issue. It’s only 10% of the group, but it is better than what we have had so far, and this is a start,” Dr. Russo said. “It’s bringing recognition to how important it is to make sure that we include underrepresented populations in these trials and also that we offer all appropriate therapies to everyone.”

Dr. Thomas reports financial relationships with Janssen, Pfizer, Biosense Webster. Dr. Russo reports no relevant financial relationships. The study was funded by the National Institutes of Health, St. Jude Medical Foundation and Corporation, Biosense Webster, Medtronic, and Boston Scientific.

A version of this article first appeared on Medscape.com.

Catheter ablation appears better than drug therapy for treating atrial fibrillation (AFib) in racial and ethnic minorities, according to a new look at CABANA trial data.

CABANA, which was undertaken to compare catheter ablation and rate-control or rhythm-control drug therapy for AFib, concluded there was no significant difference between the two strategies in improving the trial’s composite primary outcome of death, disabling stroke, serious bleeding, or cardiac arrest.

But a closer look at a subgroup of participants reveals an important difference in outcome among racial and ethnic minorities.

In that group, which made up about 10% of the CABANA study population, catheter ablation was significantly better at treating AFib than was drug therapy, producing roughly a 70% relative reduction in the primary endpoint and all-cause mortality.

The benefit for catheter ablation, which was not seen in the nonminority participants, appeared to be due to worse outcomes with drug therapy, the investigators report in an article published July 5 in the Journal of the American College of Cardiology.

“The study really highlights the importance of trying to secure an inclusive and diverse population in clinical trials,” lead author Kevin L. Thomas, MD, Duke University, Durham, N.C., said in an interview.

“When we focused on the racial and ethnic minorities who were included in CABANA, the findings were different. This was a surprise,” Dr. Thomas said.

“The findings from the secondary analysis of CABANA suggest that racial and ethnic minorities that are treated with drugs compared with ablation do worse,” he said. “If we can validate this in a larger sample of patients and this does in fact turn out to be true, then we would change how we practice medicine. We would have discussions with these populations about the benefits of ablation over drugs, and this would be important information to help guide our practice.”

The investigators analyzed data from 1,280 participants enrolled in the North American arm of CABANA. Of these, 127 (9.9%) were of racial or ethnic minorities, as defined by the National Institutes of Health, and were randomly assigned to receive ablation (n = 62) or drug therapy (n = 65).

Compared with nonminorities, participants of racial and ethnic minorities were younger (median age, 65.5 years, vs. 68.5 years) and were more likely to have NYHA functional class greater than or equal to II symptoms (37.0% vs. 22.0%), hypertension (92.1% vs. 76.8%), and an ejection fraction less than 40% (20.8% vs. 7.1%).

The overall median follow-up was 54.9 months. Among ethnic and minority participants, the median follow-up was 48 months, compared with 55.5 months for the nonminority participants.

Although there was no significant difference in the primary composite endpoint in the main CABANA trial, among racial and ethnic minorities treated with ablation, there was a 68% relative reduction in the trial’s primary endpoint (adjusted hazard ratio, 0.32; 95% confidence interval, 0.13-0.78) and a 72% relative reduction in all-cause mortality (aHR, 0.28; 95% CI, 0.10-0.79).

The 4-year Kaplan-Meier primary event rates were similar in both racial/ethnic minority and nonminority groups that received catheter ablation (12.3% vs. 9.9%).

However, the 4-year event rate was much higher among nonminority participants than among racial and ethnic minorities who received drug therapy (27.4% vs. 9.4%).

The corresponding all-cause 4-year mortality rates were 8.1% and 6.7%, respectively, in the ablation arm and 20.2% and 4.5%, respectively, in the drug arm.

Dr. Thomas and colleagues point out that heart failure in racial and ethnic minorities, particularly Black patients, is typically due to hypertensive heart disease, whereas in non-Hispanic White patients, it is overwhelmingly associated with coronary artery disease. “Our results in CABANA, therefore, raise the possibility that the variations in the prevalence of the heart diseases associated with AFib might account for differences in the benefits observed with ablation therapy.”

Prior data suggest that AFib in the setting of heart failure with either reduced or preserved ejection fraction has substantially better clinical outcomes with ablation versus drug therapy, but most studies either do not report racial/ethnic demographics or enroll very low numbers of minorities, they note.

Andrea M. Russo, MD, a professor of medicine at Rowan University, Camden, New Jersey, asks why drug therapy might result in worse outcomes in racial and ethnic minorities in an accompanying editorial.

“Those who received ablation did better than those who received drugs, and the main reason for that is not that ablation works better in minorities than nonminorities, it’s because drugs are worse in minority patients than they are in nonminority patients. This means that either the way we are using the drugs or the ones that we are using in minority patients are resulting in worse overall outcomes,” Dr. Russo told this news organization.

“The minority patients were younger and yet had more hypertension at baseline. There could be all kinds of factors contributing to their health,” she said.

Dr. Russo agrees with Dr. Thomas on the need to enroll diverse populations in clinical trials.

“Dr. Thomas should be commended. He did a fabulous job of looking at this issue. It’s only 10% of the group, but it is better than what we have had so far, and this is a start,” Dr. Russo said. “It’s bringing recognition to how important it is to make sure that we include underrepresented populations in these trials and also that we offer all appropriate therapies to everyone.”

Dr. Thomas reports financial relationships with Janssen, Pfizer, Biosense Webster. Dr. Russo reports no relevant financial relationships. The study was funded by the National Institutes of Health, St. Jude Medical Foundation and Corporation, Biosense Webster, Medtronic, and Boston Scientific.

A version of this article first appeared on Medscape.com.

Catheter ablation appears better than drug therapy for treating atrial fibrillation (AFib) in racial and ethnic minorities, according to a new look at CABANA trial data.

CABANA, which was undertaken to compare catheter ablation and rate-control or rhythm-control drug therapy for AFib, concluded there was no significant difference between the two strategies in improving the trial’s composite primary outcome of death, disabling stroke, serious bleeding, or cardiac arrest.

But a closer look at a subgroup of participants reveals an important difference in outcome among racial and ethnic minorities.

In that group, which made up about 10% of the CABANA study population, catheter ablation was significantly better at treating AFib than was drug therapy, producing roughly a 70% relative reduction in the primary endpoint and all-cause mortality.

The benefit for catheter ablation, which was not seen in the nonminority participants, appeared to be due to worse outcomes with drug therapy, the investigators report in an article published July 5 in the Journal of the American College of Cardiology.

“The study really highlights the importance of trying to secure an inclusive and diverse population in clinical trials,” lead author Kevin L. Thomas, MD, Duke University, Durham, N.C., said in an interview.

“When we focused on the racial and ethnic minorities who were included in CABANA, the findings were different. This was a surprise,” Dr. Thomas said.

“The findings from the secondary analysis of CABANA suggest that racial and ethnic minorities that are treated with drugs compared with ablation do worse,” he said. “If we can validate this in a larger sample of patients and this does in fact turn out to be true, then we would change how we practice medicine. We would have discussions with these populations about the benefits of ablation over drugs, and this would be important information to help guide our practice.”

The investigators analyzed data from 1,280 participants enrolled in the North American arm of CABANA. Of these, 127 (9.9%) were of racial or ethnic minorities, as defined by the National Institutes of Health, and were randomly assigned to receive ablation (n = 62) or drug therapy (n = 65).

Compared with nonminorities, participants of racial and ethnic minorities were younger (median age, 65.5 years, vs. 68.5 years) and were more likely to have NYHA functional class greater than or equal to II symptoms (37.0% vs. 22.0%), hypertension (92.1% vs. 76.8%), and an ejection fraction less than 40% (20.8% vs. 7.1%).

The overall median follow-up was 54.9 months. Among ethnic and minority participants, the median follow-up was 48 months, compared with 55.5 months for the nonminority participants.

Although there was no significant difference in the primary composite endpoint in the main CABANA trial, among racial and ethnic minorities treated with ablation, there was a 68% relative reduction in the trial’s primary endpoint (adjusted hazard ratio, 0.32; 95% confidence interval, 0.13-0.78) and a 72% relative reduction in all-cause mortality (aHR, 0.28; 95% CI, 0.10-0.79).

The 4-year Kaplan-Meier primary event rates were similar in both racial/ethnic minority and nonminority groups that received catheter ablation (12.3% vs. 9.9%).

However, the 4-year event rate was much higher among nonminority participants than among racial and ethnic minorities who received drug therapy (27.4% vs. 9.4%).

The corresponding all-cause 4-year mortality rates were 8.1% and 6.7%, respectively, in the ablation arm and 20.2% and 4.5%, respectively, in the drug arm.

Dr. Thomas and colleagues point out that heart failure in racial and ethnic minorities, particularly Black patients, is typically due to hypertensive heart disease, whereas in non-Hispanic White patients, it is overwhelmingly associated with coronary artery disease. “Our results in CABANA, therefore, raise the possibility that the variations in the prevalence of the heart diseases associated with AFib might account for differences in the benefits observed with ablation therapy.”

Prior data suggest that AFib in the setting of heart failure with either reduced or preserved ejection fraction has substantially better clinical outcomes with ablation versus drug therapy, but most studies either do not report racial/ethnic demographics or enroll very low numbers of minorities, they note.

Andrea M. Russo, MD, a professor of medicine at Rowan University, Camden, New Jersey, asks why drug therapy might result in worse outcomes in racial and ethnic minorities in an accompanying editorial.

“Those who received ablation did better than those who received drugs, and the main reason for that is not that ablation works better in minorities than nonminorities, it’s because drugs are worse in minority patients than they are in nonminority patients. This means that either the way we are using the drugs or the ones that we are using in minority patients are resulting in worse overall outcomes,” Dr. Russo told this news organization.

“The minority patients were younger and yet had more hypertension at baseline. There could be all kinds of factors contributing to their health,” she said.

Dr. Russo agrees with Dr. Thomas on the need to enroll diverse populations in clinical trials.

“Dr. Thomas should be commended. He did a fabulous job of looking at this issue. It’s only 10% of the group, but it is better than what we have had so far, and this is a start,” Dr. Russo said. “It’s bringing recognition to how important it is to make sure that we include underrepresented populations in these trials and also that we offer all appropriate therapies to everyone.”

Dr. Thomas reports financial relationships with Janssen, Pfizer, Biosense Webster. Dr. Russo reports no relevant financial relationships. The study was funded by the National Institutes of Health, St. Jude Medical Foundation and Corporation, Biosense Webster, Medtronic, and Boston Scientific.

A version of this article first appeared on Medscape.com.

Advanced age by itself can be a reason physicians hold back on prescribing mainstay medications, or fail to uptitrate them per guidelines, to their older patients with heart failure (HF) and reduced ejection fraction (HFrEF), suggests a large cohort study.

About 80% of patients aged 80 years or older were prescribed renin-angiotensin-system inhibitors (RASi) in a multivariate-adjusted analysis of more than 27,000 patients in the Swedish Heart Failure Registry (SwedeHF). In contrast, such drugs – which included angiotensin receptor-neprilysin inhibitors (ARNi), angiotensin receptor blockers, and ACE inhibitors – were prescribed to 95% of patients younger than 70 years.

Similarly, fewer of the oldest patients were offered meds from the two other drug classes core to HF management at the time: Beta blockers and mineralocorticoid receptor antagonists (MRA).

And among those in the 80-and-older age group who were prescribed RASi or beta blockers, their uptitration more often fell short of even half the target dosage, compared with the youngest patients in the analysis.

Physicians may hold back on full guideline-directed medical therapy in their very elderly patients with HFrEF for many reasons, including a perceived likelihood of drug intolerance due to frailty or multiple comorbidities, including renal dysfunction, Davide Stolfo, MD, Karolinska Institutet, Stockholm, and University of Trieste, Italy, told this news organization.

But the current analysis was adjusted for about 80 variables “that in our interpretation may be main reasons for not introducing drugs and using them in the older patients,” he said. They included care setting (that is, inpatient or outpatient), HF severity by several measures, a range of comorbidities, renal dysfunction, and history of serious illness such as cancer.

Even then, age emerged as a significant, independent predictor of medical therapy underuse in the oldest patients. Some physicians apparently see advanced age, by itself, as an “intrinsic reason” not to abide by HFrEF medical therapy recommendations, said Dr. Stolfo, who presented the analysis at HFA 2021, the annual meeting of the Heart Failure Association of the European Society of Cardiology (ESC-HFA), conducted both virtually and live in Florence, Italy.

Most major HF-drug trials have excluded or admitted few patients aged 80 years or older, but “the guidelines recommend treatment regardless of age, and in the trials there has been no influence from age on the effectiveness of drugs,” Dr. Stolfo observed.

Moreover, in a prior SwedeHF analysis with propensity matching, patients with HFrEF aged 80 or older showed steeper reductions in risk for death or HF hospitalization from treatment with RASi than those in younger age groups.

One of the few randomized trials to focus on the very elderly, called SENIORS, enrolled patients aged 70 years and older – the average age was 76 – and saw a significantly reduced risk of death or cardiovascular hospitalization for those assigned to the beta blocker nebivolol. The benefits in the trial, which was conducted 15 years ago, were independent of left ventricular function.

So in the oldest patients, “we could question the need to achieve full dose of an evidence-based drug, but we shouldn’t question the use of these drugs.”

The findings are consistent with a need to individualize medical therapy in senior patients with HFrEF, especially those of more advanced age, some of whom may be robust enough to be managed similarly to younger patients while others who may be less suitable for full guideline-directed medical therapy, Dr. Stolfo said.

Even for those who are more frail or have major comorbidities, drug therapy of HFrEF continues to be important for symptom control even if competing causes of death make it harder to prolong survival, Dr. Stolfo said.

“We should provide to all patients the best strategy they can tolerate,” he said. “If we cannot greatly impact on the long-term survival for these patients, treatment can be aimed to improve the quality of life and keep the patient out of the hospital.”

The analysis was supported by Boehringer Ingelheim. Dr. Stolfo disclosed personal fees from Novartis, Merck, GlaxoSmithKline, and Acceleron.

A version of this article first appeared on Medscape.com.

Advanced age by itself can be a reason physicians hold back on prescribing mainstay medications, or fail to uptitrate them per guidelines, to their older patients with heart failure (HF) and reduced ejection fraction (HFrEF), suggests a large cohort study.

About 80% of patients aged 80 years or older were prescribed renin-angiotensin-system inhibitors (RASi) in a multivariate-adjusted analysis of more than 27,000 patients in the Swedish Heart Failure Registry (SwedeHF). In contrast, such drugs – which included angiotensin receptor-neprilysin inhibitors (ARNi), angiotensin receptor blockers, and ACE inhibitors – were prescribed to 95% of patients younger than 70 years.

Similarly, fewer of the oldest patients were offered meds from the two other drug classes core to HF management at the time: Beta blockers and mineralocorticoid receptor antagonists (MRA).

And among those in the 80-and-older age group who were prescribed RASi or beta blockers, their uptitration more often fell short of even half the target dosage, compared with the youngest patients in the analysis.

Physicians may hold back on full guideline-directed medical therapy in their very elderly patients with HFrEF for many reasons, including a perceived likelihood of drug intolerance due to frailty or multiple comorbidities, including renal dysfunction, Davide Stolfo, MD, Karolinska Institutet, Stockholm, and University of Trieste, Italy, told this news organization.

But the current analysis was adjusted for about 80 variables “that in our interpretation may be main reasons for not introducing drugs and using them in the older patients,” he said. They included care setting (that is, inpatient or outpatient), HF severity by several measures, a range of comorbidities, renal dysfunction, and history of serious illness such as cancer.

Even then, age emerged as a significant, independent predictor of medical therapy underuse in the oldest patients. Some physicians apparently see advanced age, by itself, as an “intrinsic reason” not to abide by HFrEF medical therapy recommendations, said Dr. Stolfo, who presented the analysis at HFA 2021, the annual meeting of the Heart Failure Association of the European Society of Cardiology (ESC-HFA), conducted both virtually and live in Florence, Italy.

Most major HF-drug trials have excluded or admitted few patients aged 80 years or older, but “the guidelines recommend treatment regardless of age, and in the trials there has been no influence from age on the effectiveness of drugs,” Dr. Stolfo observed.

Moreover, in a prior SwedeHF analysis with propensity matching, patients with HFrEF aged 80 or older showed steeper reductions in risk for death or HF hospitalization from treatment with RASi than those in younger age groups.

One of the few randomized trials to focus on the very elderly, called SENIORS, enrolled patients aged 70 years and older – the average age was 76 – and saw a significantly reduced risk of death or cardiovascular hospitalization for those assigned to the beta blocker nebivolol. The benefits in the trial, which was conducted 15 years ago, were independent of left ventricular function.

So in the oldest patients, “we could question the need to achieve full dose of an evidence-based drug, but we shouldn’t question the use of these drugs.”

The findings are consistent with a need to individualize medical therapy in senior patients with HFrEF, especially those of more advanced age, some of whom may be robust enough to be managed similarly to younger patients while others who may be less suitable for full guideline-directed medical therapy, Dr. Stolfo said.

Even for those who are more frail or have major comorbidities, drug therapy of HFrEF continues to be important for symptom control even if competing causes of death make it harder to prolong survival, Dr. Stolfo said.

“We should provide to all patients the best strategy they can tolerate,” he said. “If we cannot greatly impact on the long-term survival for these patients, treatment can be aimed to improve the quality of life and keep the patient out of the hospital.”

The analysis was supported by Boehringer Ingelheim. Dr. Stolfo disclosed personal fees from Novartis, Merck, GlaxoSmithKline, and Acceleron.

A version of this article first appeared on Medscape.com.

Advanced age by itself can be a reason physicians hold back on prescribing mainstay medications, or fail to uptitrate them per guidelines, to their older patients with heart failure (HF) and reduced ejection fraction (HFrEF), suggests a large cohort study.

About 80% of patients aged 80 years or older were prescribed renin-angiotensin-system inhibitors (RASi) in a multivariate-adjusted analysis of more than 27,000 patients in the Swedish Heart Failure Registry (SwedeHF). In contrast, such drugs – which included angiotensin receptor-neprilysin inhibitors (ARNi), angiotensin receptor blockers, and ACE inhibitors – were prescribed to 95% of patients younger than 70 years.

Similarly, fewer of the oldest patients were offered meds from the two other drug classes core to HF management at the time: Beta blockers and mineralocorticoid receptor antagonists (MRA).

And among those in the 80-and-older age group who were prescribed RASi or beta blockers, their uptitration more often fell short of even half the target dosage, compared with the youngest patients in the analysis.

Physicians may hold back on full guideline-directed medical therapy in their very elderly patients with HFrEF for many reasons, including a perceived likelihood of drug intolerance due to frailty or multiple comorbidities, including renal dysfunction, Davide Stolfo, MD, Karolinska Institutet, Stockholm, and University of Trieste, Italy, told this news organization.

But the current analysis was adjusted for about 80 variables “that in our interpretation may be main reasons for not introducing drugs and using them in the older patients,” he said. They included care setting (that is, inpatient or outpatient), HF severity by several measures, a range of comorbidities, renal dysfunction, and history of serious illness such as cancer.

Even then, age emerged as a significant, independent predictor of medical therapy underuse in the oldest patients. Some physicians apparently see advanced age, by itself, as an “intrinsic reason” not to abide by HFrEF medical therapy recommendations, said Dr. Stolfo, who presented the analysis at HFA 2021, the annual meeting of the Heart Failure Association of the European Society of Cardiology (ESC-HFA), conducted both virtually and live in Florence, Italy.

Most major HF-drug trials have excluded or admitted few patients aged 80 years or older, but “the guidelines recommend treatment regardless of age, and in the trials there has been no influence from age on the effectiveness of drugs,” Dr. Stolfo observed.

Moreover, in a prior SwedeHF analysis with propensity matching, patients with HFrEF aged 80 or older showed steeper reductions in risk for death or HF hospitalization from treatment with RASi than those in younger age groups.

One of the few randomized trials to focus on the very elderly, called SENIORS, enrolled patients aged 70 years and older – the average age was 76 – and saw a significantly reduced risk of death or cardiovascular hospitalization for those assigned to the beta blocker nebivolol. The benefits in the trial, which was conducted 15 years ago, were independent of left ventricular function.

So in the oldest patients, “we could question the need to achieve full dose of an evidence-based drug, but we shouldn’t question the use of these drugs.”

The findings are consistent with a need to individualize medical therapy in senior patients with HFrEF, especially those of more advanced age, some of whom may be robust enough to be managed similarly to younger patients while others who may be less suitable for full guideline-directed medical therapy, Dr. Stolfo said.

Even for those who are more frail or have major comorbidities, drug therapy of HFrEF continues to be important for symptom control even if competing causes of death make it harder to prolong survival, Dr. Stolfo said.

“We should provide to all patients the best strategy they can tolerate,” he said. “If we cannot greatly impact on the long-term survival for these patients, treatment can be aimed to improve the quality of life and keep the patient out of the hospital.”

The analysis was supported by Boehringer Ingelheim. Dr. Stolfo disclosed personal fees from Novartis, Merck, GlaxoSmithKline, and Acceleron.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has approved 1-month – as short as 28 days – dual antiplatelet therapy (DAPT) labeling for Xience stents in patients at high risk for bleeding, Abbott announced on June 30.

Patients who receive stents are typically on DAPT regimens such as aspirin and P2Y12 inhibitors for 6 to 12 months to prevent blood clots, but high-bleeding risk patients can experience bleeding during prolonged DAPT.

“The new FDA approval for DAPT for the XIENCE family of stents provides interventional cardiologists confidence they are delivering the best care to patients with high bleeding risk. A short DAPT duration minimizes risks for high bleeding risk patients and allows them to return to daily life sooner and with more assurance,” Roxana Mehran, MD, Icahn School of Medicine at Mount Sinai, New York and the global principal investigator for Abbott’s Short DAPT program (XIENCE 28 and XIENCE 90), said in a news release.

The new labeling comes on the heels of European CE Mark approval for the Xience stents with DAPT as short as 28 days, “giving Xience stents the shortest DAPT indication in the world,” the company noted.

Results of the XIENCE 28 trial were used to support the new CE Mark DAPT indication. The trial showed no increase in death of myocardial infarction between 1 and 6 months and a significantly lower risk for severe bleeding with the Xience stent and 1-month DAPT, compared with 6-month DAPT in more than 1,600 high-bleeding risk patients.

The XIENCE 90 trial involving more than 2,000 high-bleeding risk patients reported no difference in death or MI between 3 and 12 months with Xience and 3-month DAPT versus 12-month DAPT.

Abbott scored a second win, also announcing FDA and CE Mark approval of its next-generation Xience Skypoint stent in high-bleeding risk patients with 1-month DAPT.

“XIENCE Skypoint is easier to place and allows physicians to treat larger blood vessels through improved stent expansion that can open clogged vessels more effectively,” the company said.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has approved 1-month – as short as 28 days – dual antiplatelet therapy (DAPT) labeling for Xience stents in patients at high risk for bleeding, Abbott announced on June 30.

Patients who receive stents are typically on DAPT regimens such as aspirin and P2Y12 inhibitors for 6 to 12 months to prevent blood clots, but high-bleeding risk patients can experience bleeding during prolonged DAPT.

“The new FDA approval for DAPT for the XIENCE family of stents provides interventional cardiologists confidence they are delivering the best care to patients with high bleeding risk. A short DAPT duration minimizes risks for high bleeding risk patients and allows them to return to daily life sooner and with more assurance,” Roxana Mehran, MD, Icahn School of Medicine at Mount Sinai, New York and the global principal investigator for Abbott’s Short DAPT program (XIENCE 28 and XIENCE 90), said in a news release.

The new labeling comes on the heels of European CE Mark approval for the Xience stents with DAPT as short as 28 days, “giving Xience stents the shortest DAPT indication in the world,” the company noted.

Results of the XIENCE 28 trial were used to support the new CE Mark DAPT indication. The trial showed no increase in death of myocardial infarction between 1 and 6 months and a significantly lower risk for severe bleeding with the Xience stent and 1-month DAPT, compared with 6-month DAPT in more than 1,600 high-bleeding risk patients.

The XIENCE 90 trial involving more than 2,000 high-bleeding risk patients reported no difference in death or MI between 3 and 12 months with Xience and 3-month DAPT versus 12-month DAPT.

Abbott scored a second win, also announcing FDA and CE Mark approval of its next-generation Xience Skypoint stent in high-bleeding risk patients with 1-month DAPT.

“XIENCE Skypoint is easier to place and allows physicians to treat larger blood vessels through improved stent expansion that can open clogged vessels more effectively,” the company said.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has approved 1-month – as short as 28 days – dual antiplatelet therapy (DAPT) labeling for Xience stents in patients at high risk for bleeding, Abbott announced on June 30.

Patients who receive stents are typically on DAPT regimens such as aspirin and P2Y12 inhibitors for 6 to 12 months to prevent blood clots, but high-bleeding risk patients can experience bleeding during prolonged DAPT.

“The new FDA approval for DAPT for the XIENCE family of stents provides interventional cardiologists confidence they are delivering the best care to patients with high bleeding risk. A short DAPT duration minimizes risks for high bleeding risk patients and allows them to return to daily life sooner and with more assurance,” Roxana Mehran, MD, Icahn School of Medicine at Mount Sinai, New York and the global principal investigator for Abbott’s Short DAPT program (XIENCE 28 and XIENCE 90), said in a news release.

The new labeling comes on the heels of European CE Mark approval for the Xience stents with DAPT as short as 28 days, “giving Xience stents the shortest DAPT indication in the world,” the company noted.

Results of the XIENCE 28 trial were used to support the new CE Mark DAPT indication. The trial showed no increase in death of myocardial infarction between 1 and 6 months and a significantly lower risk for severe bleeding with the Xience stent and 1-month DAPT, compared with 6-month DAPT in more than 1,600 high-bleeding risk patients.

The XIENCE 90 trial involving more than 2,000 high-bleeding risk patients reported no difference in death or MI between 3 and 12 months with Xience and 3-month DAPT versus 12-month DAPT.

Abbott scored a second win, also announcing FDA and CE Mark approval of its next-generation Xience Skypoint stent in high-bleeding risk patients with 1-month DAPT.

“XIENCE Skypoint is easier to place and allows physicians to treat larger blood vessels through improved stent expansion that can open clogged vessels more effectively,” the company said.

A version of this article first appeared on Medscape.com.