Cardiology News

Kevin Gendreau, MD, a weight loss doctor at Southcoast Health in Fall River, Maine, lets patients know that he was once obese. He says this knowledge inspires and motivates them to lose weight.

Courtesy Dr. Kevin Gendreau

After dropping 125 pounds over 18 months, “I can relate to their binges, hardships, and plateaus on a very personal level,” he says.

Peminda Cabandugama, MD, an endocrinologist and obesity medicine specialist at Truman Medical Center at the University of Missouri-Kansas City, has weighed between 180 and 240 pounds in the past decade. He now weighs 225 pounds and has a healthy lifestyle.

“I have had patients come to me saying, ‘I used to see a different weight loss doctor who was not heavy. But how can he understand what I’m going through?’” he says.

Dr. Cabandugama shares his weight loss struggles with patients “to dispel this myth that weight management is as simple as just eating too much and not exercising. It involves a smorgasbord of emotions and hormones, some within and outside of our control. I hope that sharing this allows me to connect more with my patients so that they know that even their health care professional goes through the same challenges that they do.”

“Patients are more likely to make behavior changes when doctors are supportive and have had similar experiences and talk about their stories,” says Wendy Bennett, MD, an obesity researcher and associate professor of medicine at Johns Hopkins University in Baltimore.

Do patients respect overweight doctors?

While Dr. Gendreau and Dr. Cabandugama have lost weight, some doctors who would like to shed unwanted pounds have been unable to do so. What impact does this have on patients?  

Doctors sometimes have biased attitudes toward overweight patients, but few studies have looked at whether patients have biases towards overweight doctors. The results vary and may depend on whether or not the patients are overweight. 

A random online survey of 358 participants suggested that regardless of their own weight, people had biases about doctor weight gain. They viewed the overweight or obese doctors as less trustworthy and credible, which could lead the participants to reject their medical advice and change doctors. 

“Patients expect doctors who are providing health care to be doing everything they can to take care of their own health and well-being,” says Pamela Peeke, MD, an assistant clinical professor of medicine at the University of Maryland in Baltimore.

“I am a physician who believes you have to walk the talk — that the best teachers are those who live it,” she says.

Still, “I don’t think based on this one experimental study that we can conclude that overweight physicians are harming patients’ efforts to change their behavior,” notes Dr. Bennett, who was not involved in the study.

“I think that patients do often want to connect with their physicians on more personal levels, but without the story behind where the advice is coming from, patients may struggle to trust a provider who seems to be contradicting the messages,” she says.

A study that Dr. Bennett helped lead suggests that patients are not biased against overweight doctors if they themselves need to lose weight. A national survey of 600 overweight patients showed that 87% trusted diet advice from overweight primary care doctors, compared to 77% who trusted diet advice from doctors who had a healthy weight.

“This shows that patients were more trusting of physicians who are more like them, which can lead to better relationships. We know from the studies on race that patients are often more trusting of physicians from the same race as them,” says Dr. Bennett.

Dr. Gendreau says that when he was severely obese, some patients questioned whether to trust his weight loss advice.

“It was very awkward when they turned to me and  said, ‘What about you?’ I would respond that it’s my job to inform them about the risks to their health,” he says.

Nearly half (48%) of doctors said they are trying to lose weight, according to the 2021 Medscape Physician Lifestyle and Happiness Report. As a result, many doctors may end up in the position of seemingly advising to “do what I say, not what I do.”

Nearly three in five Americans are trying to lose weight, according to Gelesis poll results released in December 2020.

Should doctors pay more attention to wellness?

Doctors have an ethical duty to maintain their own health and wellness so they can provide safe and effective medical care. If they don’t have a healthy lifestyle, they need to make adjustments, the American Medical Association Code of Ethics advises.

Dr. Peeke agrees with the AMA. “We signed on to do this — we have to go out of our way to carve out time, even if it’s just 15 minutes where we hide away and eat that healthy lunch that we brought with us,” she says.

Dr. Gendreau suggests busy doctors do what he did.

“I started by bringing healthy snacks — small Ziploc bags filled with mixed nuts and berries — and expanded from there. This way, if I got hungry or stressed between patients, I would have easy access to something nutritious,” he says.

He and Dr. Peeke also suggest making protein shakes or berry smoothies that are low in sugar.

“These can keep you full for hours as you sip them between patients,” says Dr. Gendreau.

Convincing busy doctors to make lifestyle changes may be challenging. Sixty-five percent of those who responded to the Physician Lifestyle and Happiness Report say that they sometimes, rarely, or never focus on their health and wellness. Only 45% said they are eating healthy, and 65% said they exercise.  

“Self-care isn’t a priority for most physicians because we are taught to take care of others and to put them first,” says Dr. Gendreau. “Like many doctors, I had so many other priorities — family, friends, career. Also, my last year of medical school was so difficult that my priority was finishing. I pushed my health to the side and told myself that I could fix this later.”

Only about one in five medical schools require students to take a nutrition course, according to David Eisenberg, MD, an adjunct associate professor of nutrition at the Harvard T.H. Chan School of Public Health, Boston.

“I didn’t get one ounce of nutrition training, which is the reason I became a Pew Foundation scholar in nutrition and metabolism. I had to go outside of my traditional training,” says Dr. Peeke.

“Physicians are not adequately trained to do the behavioral counseling and motivational interviewing that is needed,” says Dr. Bennett. “We do a good job of diagnosing obesity based on body mass index and understanding the relationship with future health conditions. But most doctors struggle with both a lack of time and the skill set to make significant behavior changes.”

“Medical school curriculum is focused so heavily on the pathology and pathophysiology of obesity, rather than how to prevent it with the appropriate diet and exercise regimen,” Dr. Gendreau says. “My physician patients often tell me that their own education in the field of nutrition is lacking, which can affect their weight loss journey and what they teach their patients.”

Dr. Gendreau, crediting his own weight loss journey as well as his obesity medicine fellowship, says his confidence in discussing weight loss with patients has soared.

Reframing obesity as a chronic disease

Rather than criticizing overweight people, including doctors, for their personal health choices, a better approach is to think of weight or obesity as a chronic illness, says Dr. Bennett.

“If we understand that obesity is a chronic health condition that people are struggling with, we can empathize with them,” she says, recommending that more providers share their weight loss journeys with patients they give lifestyle advice to, which may help address and repair potential biases.


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

Kevin Gendreau, MD, a weight loss doctor at Southcoast Health in Fall River, Maine, lets patients know that he was once obese. He says this knowledge inspires and motivates them to lose weight.

Courtesy Dr. Kevin Gendreau

After dropping 125 pounds over 18 months, “I can relate to their binges, hardships, and plateaus on a very personal level,” he says.

Peminda Cabandugama, MD, an endocrinologist and obesity medicine specialist at Truman Medical Center at the University of Missouri-Kansas City, has weighed between 180 and 240 pounds in the past decade. He now weighs 225 pounds and has a healthy lifestyle.

“I have had patients come to me saying, ‘I used to see a different weight loss doctor who was not heavy. But how can he understand what I’m going through?’” he says.

Dr. Cabandugama shares his weight loss struggles with patients “to dispel this myth that weight management is as simple as just eating too much and not exercising. It involves a smorgasbord of emotions and hormones, some within and outside of our control. I hope that sharing this allows me to connect more with my patients so that they know that even their health care professional goes through the same challenges that they do.”

“Patients are more likely to make behavior changes when doctors are supportive and have had similar experiences and talk about their stories,” says Wendy Bennett, MD, an obesity researcher and associate professor of medicine at Johns Hopkins University in Baltimore.

Do patients respect overweight doctors?

While Dr. Gendreau and Dr. Cabandugama have lost weight, some doctors who would like to shed unwanted pounds have been unable to do so. What impact does this have on patients?  

Doctors sometimes have biased attitudes toward overweight patients, but few studies have looked at whether patients have biases towards overweight doctors. The results vary and may depend on whether or not the patients are overweight. 

A random online survey of 358 participants suggested that regardless of their own weight, people had biases about doctor weight gain. They viewed the overweight or obese doctors as less trustworthy and credible, which could lead the participants to reject their medical advice and change doctors. 

“Patients expect doctors who are providing health care to be doing everything they can to take care of their own health and well-being,” says Pamela Peeke, MD, an assistant clinical professor of medicine at the University of Maryland in Baltimore.

“I am a physician who believes you have to walk the talk — that the best teachers are those who live it,” she says.

Still, “I don’t think based on this one experimental study that we can conclude that overweight physicians are harming patients’ efforts to change their behavior,” notes Dr. Bennett, who was not involved in the study.

“I think that patients do often want to connect with their physicians on more personal levels, but without the story behind where the advice is coming from, patients may struggle to trust a provider who seems to be contradicting the messages,” she says.

A study that Dr. Bennett helped lead suggests that patients are not biased against overweight doctors if they themselves need to lose weight. A national survey of 600 overweight patients showed that 87% trusted diet advice from overweight primary care doctors, compared to 77% who trusted diet advice from doctors who had a healthy weight.

“This shows that patients were more trusting of physicians who are more like them, which can lead to better relationships. We know from the studies on race that patients are often more trusting of physicians from the same race as them,” says Dr. Bennett.

Dr. Gendreau says that when he was severely obese, some patients questioned whether to trust his weight loss advice.

“It was very awkward when they turned to me and  said, ‘What about you?’ I would respond that it’s my job to inform them about the risks to their health,” he says.

Nearly half (48%) of doctors said they are trying to lose weight, according to the 2021 Medscape Physician Lifestyle and Happiness Report. As a result, many doctors may end up in the position of seemingly advising to “do what I say, not what I do.”

Nearly three in five Americans are trying to lose weight, according to Gelesis poll results released in December 2020.

Should doctors pay more attention to wellness?

Doctors have an ethical duty to maintain their own health and wellness so they can provide safe and effective medical care. If they don’t have a healthy lifestyle, they need to make adjustments, the American Medical Association Code of Ethics advises.

Dr. Peeke agrees with the AMA. “We signed on to do this — we have to go out of our way to carve out time, even if it’s just 15 minutes where we hide away and eat that healthy lunch that we brought with us,” she says.

Dr. Gendreau suggests busy doctors do what he did.

“I started by bringing healthy snacks — small Ziploc bags filled with mixed nuts and berries — and expanded from there. This way, if I got hungry or stressed between patients, I would have easy access to something nutritious,” he says.

He and Dr. Peeke also suggest making protein shakes or berry smoothies that are low in sugar.

“These can keep you full for hours as you sip them between patients,” says Dr. Gendreau.

Convincing busy doctors to make lifestyle changes may be challenging. Sixty-five percent of those who responded to the Physician Lifestyle and Happiness Report say that they sometimes, rarely, or never focus on their health and wellness. Only 45% said they are eating healthy, and 65% said they exercise.  

“Self-care isn’t a priority for most physicians because we are taught to take care of others and to put them first,” says Dr. Gendreau. “Like many doctors, I had so many other priorities — family, friends, career. Also, my last year of medical school was so difficult that my priority was finishing. I pushed my health to the side and told myself that I could fix this later.”

Only about one in five medical schools require students to take a nutrition course, according to David Eisenberg, MD, an adjunct associate professor of nutrition at the Harvard T.H. Chan School of Public Health, Boston.

“I didn’t get one ounce of nutrition training, which is the reason I became a Pew Foundation scholar in nutrition and metabolism. I had to go outside of my traditional training,” says Dr. Peeke.

“Physicians are not adequately trained to do the behavioral counseling and motivational interviewing that is needed,” says Dr. Bennett. “We do a good job of diagnosing obesity based on body mass index and understanding the relationship with future health conditions. But most doctors struggle with both a lack of time and the skill set to make significant behavior changes.”

“Medical school curriculum is focused so heavily on the pathology and pathophysiology of obesity, rather than how to prevent it with the appropriate diet and exercise regimen,” Dr. Gendreau says. “My physician patients often tell me that their own education in the field of nutrition is lacking, which can affect their weight loss journey and what they teach their patients.”

Dr. Gendreau, crediting his own weight loss journey as well as his obesity medicine fellowship, says his confidence in discussing weight loss with patients has soared.

Reframing obesity as a chronic disease

Rather than criticizing overweight people, including doctors, for their personal health choices, a better approach is to think of weight or obesity as a chronic illness, says Dr. Bennett.

“If we understand that obesity is a chronic health condition that people are struggling with, we can empathize with them,” she says, recommending that more providers share their weight loss journeys with patients they give lifestyle advice to, which may help address and repair potential biases.


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

Kevin Gendreau, MD, a weight loss doctor at Southcoast Health in Fall River, Maine, lets patients know that he was once obese. He says this knowledge inspires and motivates them to lose weight.

Courtesy Dr. Kevin Gendreau

After dropping 125 pounds over 18 months, “I can relate to their binges, hardships, and plateaus on a very personal level,” he says.

Peminda Cabandugama, MD, an endocrinologist and obesity medicine specialist at Truman Medical Center at the University of Missouri-Kansas City, has weighed between 180 and 240 pounds in the past decade. He now weighs 225 pounds and has a healthy lifestyle.

“I have had patients come to me saying, ‘I used to see a different weight loss doctor who was not heavy. But how can he understand what I’m going through?’” he says.

Dr. Cabandugama shares his weight loss struggles with patients “to dispel this myth that weight management is as simple as just eating too much and not exercising. It involves a smorgasbord of emotions and hormones, some within and outside of our control. I hope that sharing this allows me to connect more with my patients so that they know that even their health care professional goes through the same challenges that they do.”

“Patients are more likely to make behavior changes when doctors are supportive and have had similar experiences and talk about their stories,” says Wendy Bennett, MD, an obesity researcher and associate professor of medicine at Johns Hopkins University in Baltimore.

Do patients respect overweight doctors?

While Dr. Gendreau and Dr. Cabandugama have lost weight, some doctors who would like to shed unwanted pounds have been unable to do so. What impact does this have on patients?  

Doctors sometimes have biased attitudes toward overweight patients, but few studies have looked at whether patients have biases towards overweight doctors. The results vary and may depend on whether or not the patients are overweight. 

A random online survey of 358 participants suggested that regardless of their own weight, people had biases about doctor weight gain. They viewed the overweight or obese doctors as less trustworthy and credible, which could lead the participants to reject their medical advice and change doctors. 

“Patients expect doctors who are providing health care to be doing everything they can to take care of their own health and well-being,” says Pamela Peeke, MD, an assistant clinical professor of medicine at the University of Maryland in Baltimore.

“I am a physician who believes you have to walk the talk — that the best teachers are those who live it,” she says.

Still, “I don’t think based on this one experimental study that we can conclude that overweight physicians are harming patients’ efforts to change their behavior,” notes Dr. Bennett, who was not involved in the study.

“I think that patients do often want to connect with their physicians on more personal levels, but without the story behind where the advice is coming from, patients may struggle to trust a provider who seems to be contradicting the messages,” she says.

A study that Dr. Bennett helped lead suggests that patients are not biased against overweight doctors if they themselves need to lose weight. A national survey of 600 overweight patients showed that 87% trusted diet advice from overweight primary care doctors, compared to 77% who trusted diet advice from doctors who had a healthy weight.

“This shows that patients were more trusting of physicians who are more like them, which can lead to better relationships. We know from the studies on race that patients are often more trusting of physicians from the same race as them,” says Dr. Bennett.

Dr. Gendreau says that when he was severely obese, some patients questioned whether to trust his weight loss advice.

“It was very awkward when they turned to me and  said, ‘What about you?’ I would respond that it’s my job to inform them about the risks to their health,” he says.

Nearly half (48%) of doctors said they are trying to lose weight, according to the 2021 Medscape Physician Lifestyle and Happiness Report. As a result, many doctors may end up in the position of seemingly advising to “do what I say, not what I do.”

Nearly three in five Americans are trying to lose weight, according to Gelesis poll results released in December 2020.

Should doctors pay more attention to wellness?

Doctors have an ethical duty to maintain their own health and wellness so they can provide safe and effective medical care. If they don’t have a healthy lifestyle, they need to make adjustments, the American Medical Association Code of Ethics advises.

Dr. Peeke agrees with the AMA. “We signed on to do this — we have to go out of our way to carve out time, even if it’s just 15 minutes where we hide away and eat that healthy lunch that we brought with us,” she says.

Dr. Gendreau suggests busy doctors do what he did.

“I started by bringing healthy snacks — small Ziploc bags filled with mixed nuts and berries — and expanded from there. This way, if I got hungry or stressed between patients, I would have easy access to something nutritious,” he says.

He and Dr. Peeke also suggest making protein shakes or berry smoothies that are low in sugar.

“These can keep you full for hours as you sip them between patients,” says Dr. Gendreau.

Convincing busy doctors to make lifestyle changes may be challenging. Sixty-five percent of those who responded to the Physician Lifestyle and Happiness Report say that they sometimes, rarely, or never focus on their health and wellness. Only 45% said they are eating healthy, and 65% said they exercise.  

“Self-care isn’t a priority for most physicians because we are taught to take care of others and to put them first,” says Dr. Gendreau. “Like many doctors, I had so many other priorities — family, friends, career. Also, my last year of medical school was so difficult that my priority was finishing. I pushed my health to the side and told myself that I could fix this later.”

Only about one in five medical schools require students to take a nutrition course, according to David Eisenberg, MD, an adjunct associate professor of nutrition at the Harvard T.H. Chan School of Public Health, Boston.

“I didn’t get one ounce of nutrition training, which is the reason I became a Pew Foundation scholar in nutrition and metabolism. I had to go outside of my traditional training,” says Dr. Peeke.

“Physicians are not adequately trained to do the behavioral counseling and motivational interviewing that is needed,” says Dr. Bennett. “We do a good job of diagnosing obesity based on body mass index and understanding the relationship with future health conditions. But most doctors struggle with both a lack of time and the skill set to make significant behavior changes.”

“Medical school curriculum is focused so heavily on the pathology and pathophysiology of obesity, rather than how to prevent it with the appropriate diet and exercise regimen,” Dr. Gendreau says. “My physician patients often tell me that their own education in the field of nutrition is lacking, which can affect their weight loss journey and what they teach their patients.”

Dr. Gendreau, crediting his own weight loss journey as well as his obesity medicine fellowship, says his confidence in discussing weight loss with patients has soared.

Reframing obesity as a chronic disease

Rather than criticizing overweight people, including doctors, for their personal health choices, a better approach is to think of weight or obesity as a chronic illness, says Dr. Bennett.

“If we understand that obesity is a chronic health condition that people are struggling with, we can empathize with them,” she says, recommending that more providers share their weight loss journeys with patients they give lifestyle advice to, which may help address and repair potential biases.


A version of this article first appeared on WebMD.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.

Adults with limited English skills receive far less health care than do those proficient in English, according to a new study in Health Affairs.

Jessica Himmelstein, MD, a Harvard research fellow and primary care physician at Cambridge Health Alliance in Cambridge, Mass., led a study of more than 120,000 adults published July 6, 2021. The study population included 17,776 Hispanic adults with limited English proficiency, 14,936 Hispanic adults proficient in English and 87,834 non-Hispanic, English-proficient adults.

Researchers compared several measures of care usage from information in the Agency for Healthcare Research and Quality’s Medical Expenditure Panel Survey from 1998 to 2018.

They found that, in adjusted analyses, total use of care per capita from 2014-2018, measured by health care expenditures, was $1,463 lower (98% confidence interval, $1,030-$1,897), or 35% lower for primary-Spanish speakers than for Hispanic adults who were English proficient and $2,802 lower (98% CI, $2,356-$3,247), or 42% lower versus non-Hispanic adults who were English proficient.

Spanish speakers also had 36% fewer outpatient visits and 48% fewer prescription medications than non-Hispanic adults, and 35% fewer outpatient visits and 37% fewer prescription medications than English-proficient Hispanic adults.

Even when accounting for differences in health, age, sex, income and insurance, adults with language barriers fared worse.
 

Gaps span all types of care

The services that those with limited English skills are missing are “the types of care people need to lead a healthy life,” from routine visits and medications to urgent or emergency care, Dr. Himmelstein said in an interview.

She said the gaps were greater in outpatient care and in medication use, compared with emergency department visits and inpatient care, but the inequities were present in all the categories she and her coinvestigators studied.

Underlying causes for having less care may include that people who struggle with English may not feel comfortable accessing the health system or may feel unwelcome or discriminated against.

“An undercurrent of biases, including racism, could also be contributing,” she said.

The data show that, despite several federal policy changes aimed at promoting language services in hospitals and clinics, several language-based disparities have not improved over 2 decades.

Some of the changes have included an executive order in 2000 requiring interpreters to be available in federally funded health facilities. In 2010, the Affordable Care Act enhanced the definition of meaningful access to language services and setting standards for qualified interpreters.
 

Gap widened over 2 decades

The adjusted gap in annual health care expenditures per capita between adults with limited English skills and non-Hispanic, English-proficient adults widened by $1,596 (98% CI, $837-$2,356) between 1999-2000 and 2017-2018, after accounting for inflation.

Dr. Himmelstein said that though this study period predated COVID-19, its findings may help explain the disproportionate burden the pandemic placed on the Hispanic population.

“This is a community that traditionally wasn’t getting access to care and then suddenly something like COVID-19 comes and they were even more devastated,” she noted.

Telehealth, which proved an important way to access care during the pandemic, also added a degree of communication difficulty for those with fewer English skills, she said.

Many of the telehealth changes are here to stay, and it will be important to ask: “Are we ensuring equity in telehealth use for individuals who face language barriers?” Dr. Himmelstein said.

Olga Garcia-Bedoya, MD, an associate professor at University of Illinois at Chicago’s department of medicine and medical director of UIC’s Institute for Minority Health Research, said having access to interpreters with high accuracy is key to narrowing the gaps.

“The literature is very clear that access to professional medical interpreters is associated with decreased health disparities for patients with limited English proficiency,” she said.

More cultural training for clinicians is needed surrounding beliefs about illness and that some care may be declined not because of a person’s limited English proficiency, but because their beliefs may keep them from getting care, Dr. Garcia-Bedoya added. When it comes to getting a flu shot, for example, sometimes belief systems, rather than English proficiency, keep people from accessing care.
 

What can be done?

Addressing barriers caused by lack of English proficiency will likely take change in policies, including one related reimbursement for medical interpreters, Dr. Himmelstein said.

Currently, only 15 states’ Medicaid programs or Children’s Health Insurance Programs reimburse providers for language services, the paper notes, and neither Medicare nor private insurers routinely pay for those services.

Recruiting bilingual providers and staff at health care facilities and in medical and nursing schools will also be important to narrow the gaps, Dr. Himmelstein said.

Strengthening standards for interpreters also will help. “Currently such standards vary by state or by institution and are not necessarily enforced,” she explained.

It will also be important to make sure patients know that they are entitled by law to care, free of discriminatory practices and to have certain language services including qualified interpreters, Dr. Himmelstein said.

Dr. Garcia-Bedoya said changes need to come from health systems working in combination with clinicians, providing resources so that quality interpreters can be accessed and making sure that equipment supports clear communication in telehealth. Patients’ language preferences should also be noted as soon as they make the appointment.

The findings of the study may have large significance as one in seven people in the United States speak Spanish at home, and 25 million people in the United States have limited English proficiency, the authors noted.

Dr. Himmelstein receives funding support from an Institutional National Research Service Award. Dr. Garcia-Bedoya reports no relevant financial relationships.

Adults with limited English skills receive far less health care than do those proficient in English, according to a new study in Health Affairs.

Jessica Himmelstein, MD, a Harvard research fellow and primary care physician at Cambridge Health Alliance in Cambridge, Mass., led a study of more than 120,000 adults published July 6, 2021. The study population included 17,776 Hispanic adults with limited English proficiency, 14,936 Hispanic adults proficient in English and 87,834 non-Hispanic, English-proficient adults.

Researchers compared several measures of care usage from information in the Agency for Healthcare Research and Quality’s Medical Expenditure Panel Survey from 1998 to 2018.

They found that, in adjusted analyses, total use of care per capita from 2014-2018, measured by health care expenditures, was $1,463 lower (98% confidence interval, $1,030-$1,897), or 35% lower for primary-Spanish speakers than for Hispanic adults who were English proficient and $2,802 lower (98% CI, $2,356-$3,247), or 42% lower versus non-Hispanic adults who were English proficient.

Spanish speakers also had 36% fewer outpatient visits and 48% fewer prescription medications than non-Hispanic adults, and 35% fewer outpatient visits and 37% fewer prescription medications than English-proficient Hispanic adults.

Even when accounting for differences in health, age, sex, income and insurance, adults with language barriers fared worse.
 

Gaps span all types of care

The services that those with limited English skills are missing are “the types of care people need to lead a healthy life,” from routine visits and medications to urgent or emergency care, Dr. Himmelstein said in an interview.

She said the gaps were greater in outpatient care and in medication use, compared with emergency department visits and inpatient care, but the inequities were present in all the categories she and her coinvestigators studied.

Underlying causes for having less care may include that people who struggle with English may not feel comfortable accessing the health system or may feel unwelcome or discriminated against.

“An undercurrent of biases, including racism, could also be contributing,” she said.

The data show that, despite several federal policy changes aimed at promoting language services in hospitals and clinics, several language-based disparities have not improved over 2 decades.

Some of the changes have included an executive order in 2000 requiring interpreters to be available in federally funded health facilities. In 2010, the Affordable Care Act enhanced the definition of meaningful access to language services and setting standards for qualified interpreters.
 

Gap widened over 2 decades

The adjusted gap in annual health care expenditures per capita between adults with limited English skills and non-Hispanic, English-proficient adults widened by $1,596 (98% CI, $837-$2,356) between 1999-2000 and 2017-2018, after accounting for inflation.

Dr. Himmelstein said that though this study period predated COVID-19, its findings may help explain the disproportionate burden the pandemic placed on the Hispanic population.

“This is a community that traditionally wasn’t getting access to care and then suddenly something like COVID-19 comes and they were even more devastated,” she noted.

Telehealth, which proved an important way to access care during the pandemic, also added a degree of communication difficulty for those with fewer English skills, she said.

Many of the telehealth changes are here to stay, and it will be important to ask: “Are we ensuring equity in telehealth use for individuals who face language barriers?” Dr. Himmelstein said.

Olga Garcia-Bedoya, MD, an associate professor at University of Illinois at Chicago’s department of medicine and medical director of UIC’s Institute for Minority Health Research, said having access to interpreters with high accuracy is key to narrowing the gaps.

“The literature is very clear that access to professional medical interpreters is associated with decreased health disparities for patients with limited English proficiency,” she said.

More cultural training for clinicians is needed surrounding beliefs about illness and that some care may be declined not because of a person’s limited English proficiency, but because their beliefs may keep them from getting care, Dr. Garcia-Bedoya added. When it comes to getting a flu shot, for example, sometimes belief systems, rather than English proficiency, keep people from accessing care.
 

What can be done?

Addressing barriers caused by lack of English proficiency will likely take change in policies, including one related reimbursement for medical interpreters, Dr. Himmelstein said.

Currently, only 15 states’ Medicaid programs or Children’s Health Insurance Programs reimburse providers for language services, the paper notes, and neither Medicare nor private insurers routinely pay for those services.

Recruiting bilingual providers and staff at health care facilities and in medical and nursing schools will also be important to narrow the gaps, Dr. Himmelstein said.

Strengthening standards for interpreters also will help. “Currently such standards vary by state or by institution and are not necessarily enforced,” she explained.

It will also be important to make sure patients know that they are entitled by law to care, free of discriminatory practices and to have certain language services including qualified interpreters, Dr. Himmelstein said.

Dr. Garcia-Bedoya said changes need to come from health systems working in combination with clinicians, providing resources so that quality interpreters can be accessed and making sure that equipment supports clear communication in telehealth. Patients’ language preferences should also be noted as soon as they make the appointment.

The findings of the study may have large significance as one in seven people in the United States speak Spanish at home, and 25 million people in the United States have limited English proficiency, the authors noted.

Dr. Himmelstein receives funding support from an Institutional National Research Service Award. Dr. Garcia-Bedoya reports no relevant financial relationships.

Adults with limited English skills receive far less health care than do those proficient in English, according to a new study in Health Affairs.

Jessica Himmelstein, MD, a Harvard research fellow and primary care physician at Cambridge Health Alliance in Cambridge, Mass., led a study of more than 120,000 adults published July 6, 2021. The study population included 17,776 Hispanic adults with limited English proficiency, 14,936 Hispanic adults proficient in English and 87,834 non-Hispanic, English-proficient adults.

Researchers compared several measures of care usage from information in the Agency for Healthcare Research and Quality’s Medical Expenditure Panel Survey from 1998 to 2018.

They found that, in adjusted analyses, total use of care per capita from 2014-2018, measured by health care expenditures, was $1,463 lower (98% confidence interval, $1,030-$1,897), or 35% lower for primary-Spanish speakers than for Hispanic adults who were English proficient and $2,802 lower (98% CI, $2,356-$3,247), or 42% lower versus non-Hispanic adults who were English proficient.

Spanish speakers also had 36% fewer outpatient visits and 48% fewer prescription medications than non-Hispanic adults, and 35% fewer outpatient visits and 37% fewer prescription medications than English-proficient Hispanic adults.

Even when accounting for differences in health, age, sex, income and insurance, adults with language barriers fared worse.
 

Gaps span all types of care

The services that those with limited English skills are missing are “the types of care people need to lead a healthy life,” from routine visits and medications to urgent or emergency care, Dr. Himmelstein said in an interview.

She said the gaps were greater in outpatient care and in medication use, compared with emergency department visits and inpatient care, but the inequities were present in all the categories she and her coinvestigators studied.

Underlying causes for having less care may include that people who struggle with English may not feel comfortable accessing the health system or may feel unwelcome or discriminated against.

“An undercurrent of biases, including racism, could also be contributing,” she said.

The data show that, despite several federal policy changes aimed at promoting language services in hospitals and clinics, several language-based disparities have not improved over 2 decades.

Some of the changes have included an executive order in 2000 requiring interpreters to be available in federally funded health facilities. In 2010, the Affordable Care Act enhanced the definition of meaningful access to language services and setting standards for qualified interpreters.
 

Gap widened over 2 decades

The adjusted gap in annual health care expenditures per capita between adults with limited English skills and non-Hispanic, English-proficient adults widened by $1,596 (98% CI, $837-$2,356) between 1999-2000 and 2017-2018, after accounting for inflation.

Dr. Himmelstein said that though this study period predated COVID-19, its findings may help explain the disproportionate burden the pandemic placed on the Hispanic population.

“This is a community that traditionally wasn’t getting access to care and then suddenly something like COVID-19 comes and they were even more devastated,” she noted.

Telehealth, which proved an important way to access care during the pandemic, also added a degree of communication difficulty for those with fewer English skills, she said.

Many of the telehealth changes are here to stay, and it will be important to ask: “Are we ensuring equity in telehealth use for individuals who face language barriers?” Dr. Himmelstein said.

Olga Garcia-Bedoya, MD, an associate professor at University of Illinois at Chicago’s department of medicine and medical director of UIC’s Institute for Minority Health Research, said having access to interpreters with high accuracy is key to narrowing the gaps.

“The literature is very clear that access to professional medical interpreters is associated with decreased health disparities for patients with limited English proficiency,” she said.

More cultural training for clinicians is needed surrounding beliefs about illness and that some care may be declined not because of a person’s limited English proficiency, but because their beliefs may keep them from getting care, Dr. Garcia-Bedoya added. When it comes to getting a flu shot, for example, sometimes belief systems, rather than English proficiency, keep people from accessing care.
 

What can be done?

Addressing barriers caused by lack of English proficiency will likely take change in policies, including one related reimbursement for medical interpreters, Dr. Himmelstein said.

Currently, only 15 states’ Medicaid programs or Children’s Health Insurance Programs reimburse providers for language services, the paper notes, and neither Medicare nor private insurers routinely pay for those services.

Recruiting bilingual providers and staff at health care facilities and in medical and nursing schools will also be important to narrow the gaps, Dr. Himmelstein said.

Strengthening standards for interpreters also will help. “Currently such standards vary by state or by institution and are not necessarily enforced,” she explained.

It will also be important to make sure patients know that they are entitled by law to care, free of discriminatory practices and to have certain language services including qualified interpreters, Dr. Himmelstein said.

Dr. Garcia-Bedoya said changes need to come from health systems working in combination with clinicians, providing resources so that quality interpreters can be accessed and making sure that equipment supports clear communication in telehealth. Patients’ language preferences should also be noted as soon as they make the appointment.

The findings of the study may have large significance as one in seven people in the United States speak Spanish at home, and 25 million people in the United States have limited English proficiency, the authors noted.

Dr. Himmelstein receives funding support from an Institutional National Research Service Award. Dr. Garcia-Bedoya reports no relevant financial relationships.

Israeli officials are reporting a 30% decrease in the effectiveness of the Pfizer/BioNTech vaccine to prevent SARS-CoV-2 infection and mild to moderate cases of COVID-19. At the same time, protection against hospitalization and severe illness remains robust.

The country’s Ministry of Health data cited high levels of circulating Delta variant and a relaxation of public health measures in early June for the drop in the vaccine’s prevention of “breakthrough” cases from 94% to 64% in recent weeks.

However, it is important to consider the findings in context, experts cautioned.

“My overall take on this that the vaccine is highly protective against the endpoints that matter – hospitalization and severe disease,” Anna Durbin, MD, told this news organization.

“I was very pleasantly surprised with the very high efficacy against hospitalization and severe disease – even against the Delta variant,” added Dr. Durbin, professor of medicine at Johns Hopkins University, Baltimore.

Ali Mokdad, PhD, of the Institute for Health Metrics at the University of Washington, Seattle, agreed that the high degree of protection against severe outcomes should be the focus.

“That’s the whole idea. You want to defend against COVID-19. So even if someone is infected, they don’t end up in the hospital or in the morgue,” he said in an interview.

Compared with an earlier report, the efficacy of the Pfizer vaccine against hospitalization fell slightly from 98% to 93%.

“For me, the fact that there is increased infection from the Delta variant after the vaccines such as Pfizer is of course a concern. But the positive news is that there is 93% prevention against severe disease or mortality,” added Dr. Mokdad, who is also professor of global health at University of Washington.

In addition, the absolute numbers remain relatively small. The Ministry of Health data show that, of the 63 Israelis hospitalized with COVID-19 nationwide on July 3, 34 were in critical condition.
 

Unrealistic expectations?

People may have unrealistic expectations regarding breakthrough infections, Dr. Durbin said. “It seems that people are almost expecting ‘sterilizing immunity’ from these vaccines,” she said, explaining that would mean complete protection from infection.

Expectations may be high “because these vaccines have been so effective,” added Dr. Durbin, who is also affiliated with the Johns Hopkins Center for Global Health.

The higher the number of vaccinated residents, the more breakthrough cases will be reported, epidemiologist Katelyn Jetelina, PhD, MPH, assistant professor of epidemiology, human genetics, and environmental sciences at the University of Texas Science Center at Houston, wrote in her “Your Local Epidemiologist” blog.

This could apply to Israel, with an estimated 60% of adults in Israel fully vaccinated and 65% receiving at least one dose as of July 5, Our World in Data figures show.

How the updated figures were reported could be confusing, Dr. Jetelina said. Israel’s Health Minister Chezy Levy noted that “55% of the newly infected had been vaccinated” in a radio interview announcing the results.

“This language is important because it’s very different than ‘half of vaccinated people were infected,’ ” Dr. Jetelina noted.

Israel had a 7-day rolling average of 324 new confirmed COVID-19 cases as of July 5. Assuming 55% of these cases were among vaccinated people, that would mean 178 people experienced breakthrough infections.

In contrast, almost 6 million people in Israel are fully vaccinated. If 55% of them experienced breakthrough infections, the number would be much higher – more than 3 million.

Dr. Jetelina added that more details about the new Israel figures would be helpful, including the severity of COVID-19 among the vaccinated cases and breakdown of infections between adults and children.
 

Next steps

Israeli health officials are weighing the necessity of a third or booster dose of the vaccine. Whether they will reinstate public health measures to prevent spread of COVID-19 also remains unknown.

Going forward, Israel intends to study whether factors such as age, comorbidities, or time since immunization affect risk for breakthrough infections among people vaccinated against COVID-19.

“We want to prevent people from getting hospitalized, seriously ill, and of course, dying. It’s encouraging these vaccines will be able to have a high impact on those outcomes,” Dr. Durbin said. “We just need to get people vaccinated.”
 

A call for better global surveillance

A global surveillance system is a potential solution to track and respond to the growing threat of the Delta variant and other variants of concern, Scott P. Layne, MD, and Jeffery K. Taubenberger, MD, PhD, wrote in a July 7, 2021, editorial in Science Translational Medicine.

One goal, Dr. Layne said in an interview, is to highlight “the compelling need for a new global COVID-19 program of surveillance and offer a blueprint for building it.” A second aim is to promote global cooperation among key advisers and leaders in the G7, G20, and Asia-Pacific Economic Cooperation nations.

“It’s an uphill struggle with superpower discords, global warming, cybersecurity, and pandemics all competing for finite attention,” Dr. Layne said. “However, what other options do we have for taming the so-called forever virus?”

Dr. Mokdad and Dr. Jetelina had no relevant disclosures. Dr. Durban disclosed she was the site primary investigator for the phase 3 AstraZeneca vaccine trial and an investigator on the Pfizer COVID-19 vaccine trial.

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

Israeli officials are reporting a 30% decrease in the effectiveness of the Pfizer/BioNTech vaccine to prevent SARS-CoV-2 infection and mild to moderate cases of COVID-19. At the same time, protection against hospitalization and severe illness remains robust.

The country’s Ministry of Health data cited high levels of circulating Delta variant and a relaxation of public health measures in early June for the drop in the vaccine’s prevention of “breakthrough” cases from 94% to 64% in recent weeks.

However, it is important to consider the findings in context, experts cautioned.

“My overall take on this that the vaccine is highly protective against the endpoints that matter – hospitalization and severe disease,” Anna Durbin, MD, told this news organization.

“I was very pleasantly surprised with the very high efficacy against hospitalization and severe disease – even against the Delta variant,” added Dr. Durbin, professor of medicine at Johns Hopkins University, Baltimore.

Ali Mokdad, PhD, of the Institute for Health Metrics at the University of Washington, Seattle, agreed that the high degree of protection against severe outcomes should be the focus.

“That’s the whole idea. You want to defend against COVID-19. So even if someone is infected, they don’t end up in the hospital or in the morgue,” he said in an interview.

Compared with an earlier report, the efficacy of the Pfizer vaccine against hospitalization fell slightly from 98% to 93%.

“For me, the fact that there is increased infection from the Delta variant after the vaccines such as Pfizer is of course a concern. But the positive news is that there is 93% prevention against severe disease or mortality,” added Dr. Mokdad, who is also professor of global health at University of Washington.

In addition, the absolute numbers remain relatively small. The Ministry of Health data show that, of the 63 Israelis hospitalized with COVID-19 nationwide on July 3, 34 were in critical condition.
 

Unrealistic expectations?

People may have unrealistic expectations regarding breakthrough infections, Dr. Durbin said. “It seems that people are almost expecting ‘sterilizing immunity’ from these vaccines,” she said, explaining that would mean complete protection from infection.

Expectations may be high “because these vaccines have been so effective,” added Dr. Durbin, who is also affiliated with the Johns Hopkins Center for Global Health.

The higher the number of vaccinated residents, the more breakthrough cases will be reported, epidemiologist Katelyn Jetelina, PhD, MPH, assistant professor of epidemiology, human genetics, and environmental sciences at the University of Texas Science Center at Houston, wrote in her “Your Local Epidemiologist” blog.

This could apply to Israel, with an estimated 60% of adults in Israel fully vaccinated and 65% receiving at least one dose as of July 5, Our World in Data figures show.

How the updated figures were reported could be confusing, Dr. Jetelina said. Israel’s Health Minister Chezy Levy noted that “55% of the newly infected had been vaccinated” in a radio interview announcing the results.

“This language is important because it’s very different than ‘half of vaccinated people were infected,’ ” Dr. Jetelina noted.

Israel had a 7-day rolling average of 324 new confirmed COVID-19 cases as of July 5. Assuming 55% of these cases were among vaccinated people, that would mean 178 people experienced breakthrough infections.

In contrast, almost 6 million people in Israel are fully vaccinated. If 55% of them experienced breakthrough infections, the number would be much higher – more than 3 million.

Dr. Jetelina added that more details about the new Israel figures would be helpful, including the severity of COVID-19 among the vaccinated cases and breakdown of infections between adults and children.
 

Next steps

Israeli health officials are weighing the necessity of a third or booster dose of the vaccine. Whether they will reinstate public health measures to prevent spread of COVID-19 also remains unknown.

Going forward, Israel intends to study whether factors such as age, comorbidities, or time since immunization affect risk for breakthrough infections among people vaccinated against COVID-19.

“We want to prevent people from getting hospitalized, seriously ill, and of course, dying. It’s encouraging these vaccines will be able to have a high impact on those outcomes,” Dr. Durbin said. “We just need to get people vaccinated.”
 

A call for better global surveillance

A global surveillance system is a potential solution to track and respond to the growing threat of the Delta variant and other variants of concern, Scott P. Layne, MD, and Jeffery K. Taubenberger, MD, PhD, wrote in a July 7, 2021, editorial in Science Translational Medicine.

One goal, Dr. Layne said in an interview, is to highlight “the compelling need for a new global COVID-19 program of surveillance and offer a blueprint for building it.” A second aim is to promote global cooperation among key advisers and leaders in the G7, G20, and Asia-Pacific Economic Cooperation nations.

“It’s an uphill struggle with superpower discords, global warming, cybersecurity, and pandemics all competing for finite attention,” Dr. Layne said. “However, what other options do we have for taming the so-called forever virus?”

Dr. Mokdad and Dr. Jetelina had no relevant disclosures. Dr. Durban disclosed she was the site primary investigator for the phase 3 AstraZeneca vaccine trial and an investigator on the Pfizer COVID-19 vaccine trial.

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

Israeli officials are reporting a 30% decrease in the effectiveness of the Pfizer/BioNTech vaccine to prevent SARS-CoV-2 infection and mild to moderate cases of COVID-19. At the same time, protection against hospitalization and severe illness remains robust.

The country’s Ministry of Health data cited high levels of circulating Delta variant and a relaxation of public health measures in early June for the drop in the vaccine’s prevention of “breakthrough” cases from 94% to 64% in recent weeks.

However, it is important to consider the findings in context, experts cautioned.

“My overall take on this that the vaccine is highly protective against the endpoints that matter – hospitalization and severe disease,” Anna Durbin, MD, told this news organization.

“I was very pleasantly surprised with the very high efficacy against hospitalization and severe disease – even against the Delta variant,” added Dr. Durbin, professor of medicine at Johns Hopkins University, Baltimore.

Ali Mokdad, PhD, of the Institute for Health Metrics at the University of Washington, Seattle, agreed that the high degree of protection against severe outcomes should be the focus.

“That’s the whole idea. You want to defend against COVID-19. So even if someone is infected, they don’t end up in the hospital or in the morgue,” he said in an interview.

Compared with an earlier report, the efficacy of the Pfizer vaccine against hospitalization fell slightly from 98% to 93%.

“For me, the fact that there is increased infection from the Delta variant after the vaccines such as Pfizer is of course a concern. But the positive news is that there is 93% prevention against severe disease or mortality,” added Dr. Mokdad, who is also professor of global health at University of Washington.

In addition, the absolute numbers remain relatively small. The Ministry of Health data show that, of the 63 Israelis hospitalized with COVID-19 nationwide on July 3, 34 were in critical condition.
 

Unrealistic expectations?

People may have unrealistic expectations regarding breakthrough infections, Dr. Durbin said. “It seems that people are almost expecting ‘sterilizing immunity’ from these vaccines,” she said, explaining that would mean complete protection from infection.

Expectations may be high “because these vaccines have been so effective,” added Dr. Durbin, who is also affiliated with the Johns Hopkins Center for Global Health.

The higher the number of vaccinated residents, the more breakthrough cases will be reported, epidemiologist Katelyn Jetelina, PhD, MPH, assistant professor of epidemiology, human genetics, and environmental sciences at the University of Texas Science Center at Houston, wrote in her “Your Local Epidemiologist” blog.

This could apply to Israel, with an estimated 60% of adults in Israel fully vaccinated and 65% receiving at least one dose as of July 5, Our World in Data figures show.

How the updated figures were reported could be confusing, Dr. Jetelina said. Israel’s Health Minister Chezy Levy noted that “55% of the newly infected had been vaccinated” in a radio interview announcing the results.

“This language is important because it’s very different than ‘half of vaccinated people were infected,’ ” Dr. Jetelina noted.

Israel had a 7-day rolling average of 324 new confirmed COVID-19 cases as of July 5. Assuming 55% of these cases were among vaccinated people, that would mean 178 people experienced breakthrough infections.

In contrast, almost 6 million people in Israel are fully vaccinated. If 55% of them experienced breakthrough infections, the number would be much higher – more than 3 million.

Dr. Jetelina added that more details about the new Israel figures would be helpful, including the severity of COVID-19 among the vaccinated cases and breakdown of infections between adults and children.
 

Next steps

Israeli health officials are weighing the necessity of a third or booster dose of the vaccine. Whether they will reinstate public health measures to prevent spread of COVID-19 also remains unknown.

Going forward, Israel intends to study whether factors such as age, comorbidities, or time since immunization affect risk for breakthrough infections among people vaccinated against COVID-19.

“We want to prevent people from getting hospitalized, seriously ill, and of course, dying. It’s encouraging these vaccines will be able to have a high impact on those outcomes,” Dr. Durbin said. “We just need to get people vaccinated.”
 

A call for better global surveillance

A global surveillance system is a potential solution to track and respond to the growing threat of the Delta variant and other variants of concern, Scott P. Layne, MD, and Jeffery K. Taubenberger, MD, PhD, wrote in a July 7, 2021, editorial in Science Translational Medicine.

One goal, Dr. Layne said in an interview, is to highlight “the compelling need for a new global COVID-19 program of surveillance and offer a blueprint for building it.” A second aim is to promote global cooperation among key advisers and leaders in the G7, G20, and Asia-Pacific Economic Cooperation nations.

“It’s an uphill struggle with superpower discords, global warming, cybersecurity, and pandemics all competing for finite attention,” Dr. Layne said. “However, what other options do we have for taming the so-called forever virus?”

Dr. Mokdad and Dr. Jetelina had no relevant disclosures. Dr. Durban disclosed she was the site primary investigator for the phase 3 AstraZeneca vaccine trial and an investigator on the Pfizer COVID-19 vaccine trial.

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

People whose immune systems are compromised by therapy or disease may benefit from additional doses of vaccines against SARS-CoV-2, researchers say.

In a study involving 101 people with solid-organ transplants, there was a significant boost in antibodies after the patients received third doses of the Pfizer vaccine, said Nassim Kamar, MD, PhD, professor of nephrology at Toulouse University Hospital, France.

None of the transplant patients had antibodies against the virus before their first dose of the vaccine, and only 4% produced antibodies after the first dose. That proportion rose to 40% after the second dose and to 68% after the third dose.

The effect is so strong that Dr. Kamar and colleagues at Toulouse University Hospital routinely administer three doses of mRNA vaccines to patients with solid-organ transplant without testing them for antibodies.

“When we observed that the second dose was not sufficient to have an immune response, the Francophone Society of Transplantation asked the National Health Authority to allow the third dose,” he told this news organization.

That agency on April 11 approved third doses of mRNA vaccines not only for people with solid-organ transplants but also for those with recent bone marrow transplants, those undergoing dialysis, and those with autoimmune diseases who were receiving strong immunosuppressive treatment, such as anti-CD20 or antimetabolites. Contrary to their procedure for people with solid-organ transplants, clinicians at Toulouse University Hospital test these patients for antibodies and administer third doses of vaccine only to those who test negative or have very low titers.

The researchers’ findings, published on June 23 as a letter to the editor of The New England Journal of Medicine, come as other researchers document more and more categories of patients whose responses to the vaccines typically fall short.

A study at the University of Pittsburgh that was published as a preprint on MedRxiv compared people with various health conditions to healthy health care workers. People with HIV who were taking antivirals against that virus responded almost as well as did the health care workers, said John Mellors, MD, chief of infectious diseases at the university. But people whose immune systems were compromised for other reasons fared less well.

“The areas of concern are hematological malignancy and solid-organ transplants, with the most nonresponsive groups being those who have had lung transplantation,” he said in an interview.

For patients with liver disease, mixed news came from the International Liver Congress (ILC) 2021 annual meeting.

In a study involving patients with liver disease who had received the Pfizer vaccine at Hadassah University Medical Center in Jerusalem, antibody titers were lower in patients who had received liver transplants or who had advanced liver fibrosis, as reported by this news organization.

A multicenter study in China that was presented at the ILC meeting and that was also published in the Journal of Hepatology, provided a more optimistic picture. Among patients with nonalcoholic fatty liver disease who were immunized against SARS-CoV-2 with the Sinopharm vaccine, 95.5% had neutralizing antibodies; the median neutralizing antibody titer was 32.

In the Toulouse University Hospital study, for the 40 patients who were seropositive after the second dose, antibody titers increased from 36 before the third dose to 2,676 a month after the third dose, a statistically significant result (P < .001).

For patients whose immune systems are compromised for reasons other than having received a transplant, clinicians at Toulouse University Hospital use a titer of 14 as the threshold below which they administer a third dose of mRNA vaccines. But Dr. Kamar acknowledged that the threshold is arbitrary and that the assays for antibodies with different vaccines in different populations can’t be compared head to head.

“We can’t tell you simply on the basis of the amount of antibody in your laboratory report how protected you are,” agreed William Schaffner, MD, professor of infectious diseases at Vanderbilt University, Nashville, Tenn., who is a spokesperson for the Infectious Diseases Society of America.

Not enough research has been done to establish that relationship, and results vary from one laboratory to another, he said.

That doesn’t mean that antibody tests don’t help, Dr. Schaffner said. On the basis of views of other experts he has consulted, Dr. Schaffner recommends that people who are immunocompromised undergo an antibody test. If the test is positive – meaning they have some antibodies to SARS-CoV-2, however low the titers – patients can take fewer precautions than before they were vaccinated.

But they should still be more cautious than people with healthy immune systems, he said. “Would I be going to large indoor gatherings without a mask? No. Would I be outside without a mask? Yes. Would I gather with three other people who are vaccinated to play a game of bridge? Yes. You have to titrate things a little and use some common sense,” he added.

If the results are negative, such patients may still be protected. Much research remains to be done on T-cell immunity, a second line of defense against the virus. And the current assays often produce false negative results. But to be on the safe side, people with this result should assume that their vaccine is not protecting them, Dr. Schaffner said.

That suggestion contradicts the Food and Drug Administration, which issued a recommendation on May 19 against using antibody tests to check the effectiveness of SARS-CoV-2 vaccination.

The studies so far suggest that vaccines are safe for people whose immune systems are compromised, Dr. Schaffner and Dr. Kamar agreed. Dr. Kamar is aware of only two case reports of transplant patients rejecting their transplants after vaccination. One of these was his own patient, and the rejection occurred after her second dose. She has not needed dialysis, although her kidney function was impaired.

But the FDA has not approved additional doses of SARS-CoV-2 vaccine to treat patients who are immunocompromised, and Dr. Kamar has not heard of any other national regulatory agencies that have.

In the United States, it may be difficult for anyone to obtain a third dose of vaccine outside of a clinical trial, Dr. Schaffner said, because vaccinators are likely to check databases and deny vaccination to anyone who has already received the recommended number.

Dr. Kamar, Dr. Mellors, and Dr. Schaffner have disclosed no relevant financial relationships.

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

People whose immune systems are compromised by therapy or disease may benefit from additional doses of vaccines against SARS-CoV-2, researchers say.

In a study involving 101 people with solid-organ transplants, there was a significant boost in antibodies after the patients received third doses of the Pfizer vaccine, said Nassim Kamar, MD, PhD, professor of nephrology at Toulouse University Hospital, France.

None of the transplant patients had antibodies against the virus before their first dose of the vaccine, and only 4% produced antibodies after the first dose. That proportion rose to 40% after the second dose and to 68% after the third dose.

The effect is so strong that Dr. Kamar and colleagues at Toulouse University Hospital routinely administer three doses of mRNA vaccines to patients with solid-organ transplant without testing them for antibodies.

“When we observed that the second dose was not sufficient to have an immune response, the Francophone Society of Transplantation asked the National Health Authority to allow the third dose,” he told this news organization.

That agency on April 11 approved third doses of mRNA vaccines not only for people with solid-organ transplants but also for those with recent bone marrow transplants, those undergoing dialysis, and those with autoimmune diseases who were receiving strong immunosuppressive treatment, such as anti-CD20 or antimetabolites. Contrary to their procedure for people with solid-organ transplants, clinicians at Toulouse University Hospital test these patients for antibodies and administer third doses of vaccine only to those who test negative or have very low titers.

The researchers’ findings, published on June 23 as a letter to the editor of The New England Journal of Medicine, come as other researchers document more and more categories of patients whose responses to the vaccines typically fall short.

A study at the University of Pittsburgh that was published as a preprint on MedRxiv compared people with various health conditions to healthy health care workers. People with HIV who were taking antivirals against that virus responded almost as well as did the health care workers, said John Mellors, MD, chief of infectious diseases at the university. But people whose immune systems were compromised for other reasons fared less well.

“The areas of concern are hematological malignancy and solid-organ transplants, with the most nonresponsive groups being those who have had lung transplantation,” he said in an interview.

For patients with liver disease, mixed news came from the International Liver Congress (ILC) 2021 annual meeting.

In a study involving patients with liver disease who had received the Pfizer vaccine at Hadassah University Medical Center in Jerusalem, antibody titers were lower in patients who had received liver transplants or who had advanced liver fibrosis, as reported by this news organization.

A multicenter study in China that was presented at the ILC meeting and that was also published in the Journal of Hepatology, provided a more optimistic picture. Among patients with nonalcoholic fatty liver disease who were immunized against SARS-CoV-2 with the Sinopharm vaccine, 95.5% had neutralizing antibodies; the median neutralizing antibody titer was 32.

In the Toulouse University Hospital study, for the 40 patients who were seropositive after the second dose, antibody titers increased from 36 before the third dose to 2,676 a month after the third dose, a statistically significant result (P < .001).

For patients whose immune systems are compromised for reasons other than having received a transplant, clinicians at Toulouse University Hospital use a titer of 14 as the threshold below which they administer a third dose of mRNA vaccines. But Dr. Kamar acknowledged that the threshold is arbitrary and that the assays for antibodies with different vaccines in different populations can’t be compared head to head.

“We can’t tell you simply on the basis of the amount of antibody in your laboratory report how protected you are,” agreed William Schaffner, MD, professor of infectious diseases at Vanderbilt University, Nashville, Tenn., who is a spokesperson for the Infectious Diseases Society of America.

Not enough research has been done to establish that relationship, and results vary from one laboratory to another, he said.

That doesn’t mean that antibody tests don’t help, Dr. Schaffner said. On the basis of views of other experts he has consulted, Dr. Schaffner recommends that people who are immunocompromised undergo an antibody test. If the test is positive – meaning they have some antibodies to SARS-CoV-2, however low the titers – patients can take fewer precautions than before they were vaccinated.

But they should still be more cautious than people with healthy immune systems, he said. “Would I be going to large indoor gatherings without a mask? No. Would I be outside without a mask? Yes. Would I gather with three other people who are vaccinated to play a game of bridge? Yes. You have to titrate things a little and use some common sense,” he added.

If the results are negative, such patients may still be protected. Much research remains to be done on T-cell immunity, a second line of defense against the virus. And the current assays often produce false negative results. But to be on the safe side, people with this result should assume that their vaccine is not protecting them, Dr. Schaffner said.

That suggestion contradicts the Food and Drug Administration, which issued a recommendation on May 19 against using antibody tests to check the effectiveness of SARS-CoV-2 vaccination.

The studies so far suggest that vaccines are safe for people whose immune systems are compromised, Dr. Schaffner and Dr. Kamar agreed. Dr. Kamar is aware of only two case reports of transplant patients rejecting their transplants after vaccination. One of these was his own patient, and the rejection occurred after her second dose. She has not needed dialysis, although her kidney function was impaired.

But the FDA has not approved additional doses of SARS-CoV-2 vaccine to treat patients who are immunocompromised, and Dr. Kamar has not heard of any other national regulatory agencies that have.

In the United States, it may be difficult for anyone to obtain a third dose of vaccine outside of a clinical trial, Dr. Schaffner said, because vaccinators are likely to check databases and deny vaccination to anyone who has already received the recommended number.

Dr. Kamar, Dr. Mellors, and Dr. Schaffner have disclosed no relevant financial relationships.

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

People whose immune systems are compromised by therapy or disease may benefit from additional doses of vaccines against SARS-CoV-2, researchers say.

In a study involving 101 people with solid-organ transplants, there was a significant boost in antibodies after the patients received third doses of the Pfizer vaccine, said Nassim Kamar, MD, PhD, professor of nephrology at Toulouse University Hospital, France.

None of the transplant patients had antibodies against the virus before their first dose of the vaccine, and only 4% produced antibodies after the first dose. That proportion rose to 40% after the second dose and to 68% after the third dose.

The effect is so strong that Dr. Kamar and colleagues at Toulouse University Hospital routinely administer three doses of mRNA vaccines to patients with solid-organ transplant without testing them for antibodies.

“When we observed that the second dose was not sufficient to have an immune response, the Francophone Society of Transplantation asked the National Health Authority to allow the third dose,” he told this news organization.

That agency on April 11 approved third doses of mRNA vaccines not only for people with solid-organ transplants but also for those with recent bone marrow transplants, those undergoing dialysis, and those with autoimmune diseases who were receiving strong immunosuppressive treatment, such as anti-CD20 or antimetabolites. Contrary to their procedure for people with solid-organ transplants, clinicians at Toulouse University Hospital test these patients for antibodies and administer third doses of vaccine only to those who test negative or have very low titers.

The researchers’ findings, published on June 23 as a letter to the editor of The New England Journal of Medicine, come as other researchers document more and more categories of patients whose responses to the vaccines typically fall short.

A study at the University of Pittsburgh that was published as a preprint on MedRxiv compared people with various health conditions to healthy health care workers. People with HIV who were taking antivirals against that virus responded almost as well as did the health care workers, said John Mellors, MD, chief of infectious diseases at the university. But people whose immune systems were compromised for other reasons fared less well.

“The areas of concern are hematological malignancy and solid-organ transplants, with the most nonresponsive groups being those who have had lung transplantation,” he said in an interview.

For patients with liver disease, mixed news came from the International Liver Congress (ILC) 2021 annual meeting.

In a study involving patients with liver disease who had received the Pfizer vaccine at Hadassah University Medical Center in Jerusalem, antibody titers were lower in patients who had received liver transplants or who had advanced liver fibrosis, as reported by this news organization.

A multicenter study in China that was presented at the ILC meeting and that was also published in the Journal of Hepatology, provided a more optimistic picture. Among patients with nonalcoholic fatty liver disease who were immunized against SARS-CoV-2 with the Sinopharm vaccine, 95.5% had neutralizing antibodies; the median neutralizing antibody titer was 32.

In the Toulouse University Hospital study, for the 40 patients who were seropositive after the second dose, antibody titers increased from 36 before the third dose to 2,676 a month after the third dose, a statistically significant result (P < .001).

For patients whose immune systems are compromised for reasons other than having received a transplant, clinicians at Toulouse University Hospital use a titer of 14 as the threshold below which they administer a third dose of mRNA vaccines. But Dr. Kamar acknowledged that the threshold is arbitrary and that the assays for antibodies with different vaccines in different populations can’t be compared head to head.

“We can’t tell you simply on the basis of the amount of antibody in your laboratory report how protected you are,” agreed William Schaffner, MD, professor of infectious diseases at Vanderbilt University, Nashville, Tenn., who is a spokesperson for the Infectious Diseases Society of America.

Not enough research has been done to establish that relationship, and results vary from one laboratory to another, he said.

That doesn’t mean that antibody tests don’t help, Dr. Schaffner said. On the basis of views of other experts he has consulted, Dr. Schaffner recommends that people who are immunocompromised undergo an antibody test. If the test is positive – meaning they have some antibodies to SARS-CoV-2, however low the titers – patients can take fewer precautions than before they were vaccinated.

But they should still be more cautious than people with healthy immune systems, he said. “Would I be going to large indoor gatherings without a mask? No. Would I be outside without a mask? Yes. Would I gather with three other people who are vaccinated to play a game of bridge? Yes. You have to titrate things a little and use some common sense,” he added.

If the results are negative, such patients may still be protected. Much research remains to be done on T-cell immunity, a second line of defense against the virus. And the current assays often produce false negative results. But to be on the safe side, people with this result should assume that their vaccine is not protecting them, Dr. Schaffner said.

That suggestion contradicts the Food and Drug Administration, which issued a recommendation on May 19 against using antibody tests to check the effectiveness of SARS-CoV-2 vaccination.

The studies so far suggest that vaccines are safe for people whose immune systems are compromised, Dr. Schaffner and Dr. Kamar agreed. Dr. Kamar is aware of only two case reports of transplant patients rejecting their transplants after vaccination. One of these was his own patient, and the rejection occurred after her second dose. She has not needed dialysis, although her kidney function was impaired.

But the FDA has not approved additional doses of SARS-CoV-2 vaccine to treat patients who are immunocompromised, and Dr. Kamar has not heard of any other national regulatory agencies that have.

In the United States, it may be difficult for anyone to obtain a third dose of vaccine outside of a clinical trial, Dr. Schaffner said, because vaccinators are likely to check databases and deny vaccination to anyone who has already received the recommended number.

Dr. Kamar, Dr. Mellors, and Dr. Schaffner have disclosed no relevant financial relationships.

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

Insert clove A into nostril B

Just when you start wondering what crazy and potentially dangerous thing people can do to themselves next, comes a crazy and potentially dangerous new trend. The good folks at TikTok have provided patients a new treatment for stuffed up sinuses.

Dangerous? Well, that’s what doctors say, anyway.

“We typically do not recommend putting anything into the nostril for the obvious fact that it could get dislodged or lodged up into the nasal cavity,” Anthony Del Signore, MD, of Mount Sinai Union Square, New York, told TODAY.

“Not only does it have the potential to rot or cause a nasal obstruction, it can induce an episode of sinusitis,” Omid Mehdizadeh, MD, of Providence Saint John’s Health Center, Santa Monica, Calif., explained to Shape.

But who doesn't want to breathe easier and keep blood-sucking vampires at bay?

Max Pixel

Seeing faces in random places?

Ever look up at the clouds, at a fast-moving train, or into your morning bowl of cereal and see two eyes, a nose, and a mouth looking back at you? You may shake it off and think you’re imagining something, but it's actually your brain doing what it’s built to do and researchers know why.

The phenomenon is called face pareidolia, and it’s technically an error function of the human brain. Evolution has molded our brains to rapidly identify faces, according to David Alais, PhD, of the University of Sydney, Australia, lead author of the study.

“But the system plays ‘fast and loose’ by applying a crude template of two eyes over a nose and mouth. Lots of things can satisfy that template and thus trigger a face detection response,” he said in a separate statement. But not only are we seeing faces, our brains go one step further and seemingly give those faces feelings.

University of Sydney

Corporate dream manipulation

Advertisements are quite literally everywhere. On billboards, in commercials, in videos, in movies; the list goes on and on. Still, at least you can shut your eyes and be mercifully free of corporate interference inside your own head, right? Right?

Early in 2021, Coors launched an ad campaign that seemed to be a b bit of a gimmick, if not a joke. Coors claimed that if people watched an ad before bed, and played an 8-hour soundscape while sleeping, their dreams would be filled with crisp mountains and cold, thirst-quenching beverages. While, the Coors campaign didn’t go viral, someone was paying attention. A group of 35 leading researchers published an open letter on the subject of corporate dream manipulation, in the journal Dream Engineering.

"Multiple marketing studies are openly testing new ways to alter and motivate purchasing behavior through dream and sleep hacking. The commercial, for-profit use of dream incubation is rapidly becoming a reality," wrote the investigators. "As sleep and dream researchers, we are deeply concerned about marketing plans aimed at generating profits at the cost of interfering with our natural nocturnal memory processing."

People have tried to manipulate their dreams for countless years, but only in recent years have scientists attempted to target or manipulate behavior through dreams. In a 2014 study, smokers exposed to tobacco smoke and rotten egg smell while sleeping reduced their cigarette consumption by 30%.

Free-Photos/Pixabay

Got breast milk?

As we know, breast milk has endless benefits for newbords and babies, but many things can stand in the way of a mother’s ability to breastfeed. Baby formula has served as a good enough substitute. But now, there might be something that’s even better.

A start-up company called BIOMILQ created a product that could be groundbreaking. Using “breakthrough mammary biotechnology,” BIOMILQ created cell-cultured breast milk.

Focus_on_Nature/Getty Images

Insert clove A into nostril B

Just when you start wondering what crazy and potentially dangerous thing people can do to themselves next, comes a crazy and potentially dangerous new trend. The good folks at TikTok have provided patients a new treatment for stuffed up sinuses.

Dangerous? Well, that’s what doctors say, anyway.

“We typically do not recommend putting anything into the nostril for the obvious fact that it could get dislodged or lodged up into the nasal cavity,” Anthony Del Signore, MD, of Mount Sinai Union Square, New York, told TODAY.

“Not only does it have the potential to rot or cause a nasal obstruction, it can induce an episode of sinusitis,” Omid Mehdizadeh, MD, of Providence Saint John’s Health Center, Santa Monica, Calif., explained to Shape.

But who doesn't want to breathe easier and keep blood-sucking vampires at bay?

Max Pixel

Seeing faces in random places?

Ever look up at the clouds, at a fast-moving train, or into your morning bowl of cereal and see two eyes, a nose, and a mouth looking back at you? You may shake it off and think you’re imagining something, but it's actually your brain doing what it’s built to do and researchers know why.

The phenomenon is called face pareidolia, and it’s technically an error function of the human brain. Evolution has molded our brains to rapidly identify faces, according to David Alais, PhD, of the University of Sydney, Australia, lead author of the study.

“But the system plays ‘fast and loose’ by applying a crude template of two eyes over a nose and mouth. Lots of things can satisfy that template and thus trigger a face detection response,” he said in a separate statement. But not only are we seeing faces, our brains go one step further and seemingly give those faces feelings.

University of Sydney

Corporate dream manipulation

Advertisements are quite literally everywhere. On billboards, in commercials, in videos, in movies; the list goes on and on. Still, at least you can shut your eyes and be mercifully free of corporate interference inside your own head, right? Right?

Early in 2021, Coors launched an ad campaign that seemed to be a b bit of a gimmick, if not a joke. Coors claimed that if people watched an ad before bed, and played an 8-hour soundscape while sleeping, their dreams would be filled with crisp mountains and cold, thirst-quenching beverages. While, the Coors campaign didn’t go viral, someone was paying attention. A group of 35 leading researchers published an open letter on the subject of corporate dream manipulation, in the journal Dream Engineering.

"Multiple marketing studies are openly testing new ways to alter and motivate purchasing behavior through dream and sleep hacking. The commercial, for-profit use of dream incubation is rapidly becoming a reality," wrote the investigators. "As sleep and dream researchers, we are deeply concerned about marketing plans aimed at generating profits at the cost of interfering with our natural nocturnal memory processing."

People have tried to manipulate their dreams for countless years, but only in recent years have scientists attempted to target or manipulate behavior through dreams. In a 2014 study, smokers exposed to tobacco smoke and rotten egg smell while sleeping reduced their cigarette consumption by 30%.

Free-Photos/Pixabay

Got breast milk?

As we know, breast milk has endless benefits for newbords and babies, but many things can stand in the way of a mother’s ability to breastfeed. Baby formula has served as a good enough substitute. But now, there might be something that’s even better.

A start-up company called BIOMILQ created a product that could be groundbreaking. Using “breakthrough mammary biotechnology,” BIOMILQ created cell-cultured breast milk.

Focus_on_Nature/Getty Images

Insert clove A into nostril B

Just when you start wondering what crazy and potentially dangerous thing people can do to themselves next, comes a crazy and potentially dangerous new trend. The good folks at TikTok have provided patients a new treatment for stuffed up sinuses.

Dangerous? Well, that’s what doctors say, anyway.

“We typically do not recommend putting anything into the nostril for the obvious fact that it could get dislodged or lodged up into the nasal cavity,” Anthony Del Signore, MD, of Mount Sinai Union Square, New York, told TODAY.

“Not only does it have the potential to rot or cause a nasal obstruction, it can induce an episode of sinusitis,” Omid Mehdizadeh, MD, of Providence Saint John’s Health Center, Santa Monica, Calif., explained to Shape.

But who doesn't want to breathe easier and keep blood-sucking vampires at bay?

Max Pixel

Seeing faces in random places?

Ever look up at the clouds, at a fast-moving train, or into your morning bowl of cereal and see two eyes, a nose, and a mouth looking back at you? You may shake it off and think you’re imagining something, but it's actually your brain doing what it’s built to do and researchers know why.

The phenomenon is called face pareidolia, and it’s technically an error function of the human brain. Evolution has molded our brains to rapidly identify faces, according to David Alais, PhD, of the University of Sydney, Australia, lead author of the study.

“But the system plays ‘fast and loose’ by applying a crude template of two eyes over a nose and mouth. Lots of things can satisfy that template and thus trigger a face detection response,” he said in a separate statement. But not only are we seeing faces, our brains go one step further and seemingly give those faces feelings.

University of Sydney

Corporate dream manipulation

Advertisements are quite literally everywhere. On billboards, in commercials, in videos, in movies; the list goes on and on. Still, at least you can shut your eyes and be mercifully free of corporate interference inside your own head, right? Right?

Early in 2021, Coors launched an ad campaign that seemed to be a b bit of a gimmick, if not a joke. Coors claimed that if people watched an ad before bed, and played an 8-hour soundscape while sleeping, their dreams would be filled with crisp mountains and cold, thirst-quenching beverages. While, the Coors campaign didn’t go viral, someone was paying attention. A group of 35 leading researchers published an open letter on the subject of corporate dream manipulation, in the journal Dream Engineering.

"Multiple marketing studies are openly testing new ways to alter and motivate purchasing behavior through dream and sleep hacking. The commercial, for-profit use of dream incubation is rapidly becoming a reality," wrote the investigators. "As sleep and dream researchers, we are deeply concerned about marketing plans aimed at generating profits at the cost of interfering with our natural nocturnal memory processing."

People have tried to manipulate their dreams for countless years, but only in recent years have scientists attempted to target or manipulate behavior through dreams. In a 2014 study, smokers exposed to tobacco smoke and rotten egg smell while sleeping reduced their cigarette consumption by 30%.

Free-Photos/Pixabay

Got breast milk?

As we know, breast milk has endless benefits for newbords and babies, but many things can stand in the way of a mother’s ability to breastfeed. Baby formula has served as a good enough substitute. But now, there might be something that’s even better.

A start-up company called BIOMILQ created a product that could be groundbreaking. Using “breakthrough mammary biotechnology,” BIOMILQ created cell-cultured breast milk.

Focus_on_Nature/Getty Images

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.