Lipid Disorders

Women cardiologists receive dramatically smaller payments from the U.S. Centers for Medicare & Medicaid Services (CMS) than their male counterparts, new research suggests.

An analysis of 2016 claims data revealed male cardiologists received on average 45% more reimbursement than women in the inpatient setting, with the median payment 39% higher ($62,897 vs. $45,288).

In the outpatient setting, men received on average 62% more annual CMS payments, with the median payment 75% higher ($91,053 vs. $51,975; P < .001 for both).

The difference remained significant after the exclusion of the top and bottom 2.5% of earning physicians and cardiology subspecialties, like electrophysiology and interventional cardiology, with high procedural volumes and greater gender imbalances.

“This is one study among others which demonstrates a wage gap between men and women in medicine in cardiology,” lead author Inbar Raber, MD, Beth Israel Deaconess Medical Center, Boston, said in an interview. “I hope by increasing awareness [and] understanding of possible etiologies, it will enable some sustainable solutions, and those include access to additional support staff and equitable models surrounding parental leave and childcare support.”

The study, published online September 8 in JAMA Cardiology, comes on the heels of a recent cross-sectional analysis that put cardiology at the bottom of 13 internal medicine subspecialties with just 21% female faculty representation and one of only three specialties in which women’s median salaries did not reach 90% of men’s.

The new findings build on a 2017 report that showed Medicare payments to women physicians in 2013 were 55% of those to male physicians across all specialties.  

“It can be disheartening, especially as an early career woman cardiologist, seeing these differences, but I think the responsibility on all of us is to take these observations and really try to understand more deeply why they exist,” Nosheen Reza, MD, from the University of Pennsylvania, Philadelphia, and coauthor of the cross-sectional analysis, told this news organization.

Several factors could be contributing to the disparity, but “it’s not gender discrimination from Medicare,” Dr. Raber said. “The gap in reimbursement is really driven by the types and the volume of charges submitted.”

Indeed, a direct comparison of the three most common inpatient and outpatient billing codes showed no difference in payments between the sexes.

Men, however, submitted 24% more median inpatient charges to CMS than women (1,190 vs. 959), and 94% more outpatient charges (1,685 vs. 870).

Men also submitted slightly more unique billing codes (median inpatient, 10 vs. 9; median outpatient, 11 vs. 8).

Notably, women made up just 13% of the 17,524 cardiologists who received CMS payments in the inpatient setting in 2016 and 13% of the 16,929 cardiologists who did so in the outpatient setting.

Louisiana had the dubious distinction of having the largest gender gap in mean CMS payments, with male cardiologists earning $145,323 (235%) more than women, whereas women cardiologists in Vermont out-earned men by $31,483 (38%).

Overall, male cardiologists had more years in practice than women cardiologists and cared for slightly older Medicare beneficiaries.

Differences in CMS payments persisted, however, after adjustment for years since graduation, physician subspecialty, number of charges, number of unique billing codes, and patient complexity. The resulting β coefficient was -0.06, which translates into women receiving an average of 94% of the CMS payments received by men.

“The first takeaway, if you were really crass and focused on the bottom line, might be: ‘Hey, let me get a few more male cardiologists because they’re going to bring more into the organization.’ But we shouldn’t do that because, unless you link these data with quality outcomes, they’re an interesting observation and hypothesis-generating,” said Sharonne Hayes, MD, coauthor of the 2017 report and professor of cardiovascular medicine at Mayo Clinic in Rochester, Minn., where she has served as director of diversity and inclusion for a decade.

She noted that there are multiple examples that the style of medicine women practice, on average, may be more effective, may be more outcomes based, and may save lives, as suggested by a recent analysis of hospitalized Medicare beneficiaries.

“The gap was not much different, like within 1% or so, but when you take that over the literally millions of Medicare patients cared for each year by hospitalists, that’s a substantial number of people,” Dr. Hayes said. “So, I think we need to take a step back, and we have to include these observations on studies like this and better understand the compensation gaps.”

She pointed out that the present study lacks data on full-time-equivalent status but that female physicians are more likely to work part-time, thus reducing the volume of claims.

Women might also care for different patient populations. “I practice in a women’s heart clinic and take care of [spontaneous coronary artery dissection] SCAD patients where the average age of SCAD is 42. So, the vast majority of patients I see on a day-to-day basis aren’t going to be Medicare age,” observed Dr. Hayes.

The differences in charges might also reflect the increased obligations in nonreimbursed work that women can have, Dr. Raber said. These can be things like mentoring, teaching roles, and serving on committees, which is a hypothesis supported by a 2021 study that showed women physicians spend more time on these “citizenship tasks” than men.

Finally, there could be organizational barriers that affect women’s clinical volumes, including less access to support from health care personnel. Added support is especially important, though, amid a 100-year pandemic, the women agreed.

“Within the first year of the pandemic, we saw women leaving the workforce in droves across all sectors, including medicine, including academic medicine. And, as the pandemic goes on without any signs of abatement, those threats continue to exist and continue to be amplified,” Dr. Reza said.

The groundswell of support surrounding the importance of diversity, equity, and inclusion initiatives across the board has helped bring attention to the issue, she said. Some institutions, including the National Institutes of Health, are making efforts to extend relief to women with young families, caregivers, or those in academic medicine who, for example, need extensions on grants or bridge funding.

“There’s certainly a lot left to do, but I do think within the last year, there’s been an acceleration of literature that has come out, not only pointing out the disparities, but pointing out that perhaps women physicians do have better outcomes and are better liked by their patients and that losing women in the workforce would be a huge detriment to the field overall,” Dr. Reza said.

Dr. Raber, Dr. Reza, and Dr. Hayes reports no relevant financial relationships. Coauthor conflict of interest disclosures are listed in the paper.

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

Women cardiologists receive dramatically smaller payments from the U.S. Centers for Medicare & Medicaid Services (CMS) than their male counterparts, new research suggests.

An analysis of 2016 claims data revealed male cardiologists received on average 45% more reimbursement than women in the inpatient setting, with the median payment 39% higher ($62,897 vs. $45,288).

In the outpatient setting, men received on average 62% more annual CMS payments, with the median payment 75% higher ($91,053 vs. $51,975; P < .001 for both).

The difference remained significant after the exclusion of the top and bottom 2.5% of earning physicians and cardiology subspecialties, like electrophysiology and interventional cardiology, with high procedural volumes and greater gender imbalances.

“This is one study among others which demonstrates a wage gap between men and women in medicine in cardiology,” lead author Inbar Raber, MD, Beth Israel Deaconess Medical Center, Boston, said in an interview. “I hope by increasing awareness [and] understanding of possible etiologies, it will enable some sustainable solutions, and those include access to additional support staff and equitable models surrounding parental leave and childcare support.”

The study, published online September 8 in JAMA Cardiology, comes on the heels of a recent cross-sectional analysis that put cardiology at the bottom of 13 internal medicine subspecialties with just 21% female faculty representation and one of only three specialties in which women’s median salaries did not reach 90% of men’s.

The new findings build on a 2017 report that showed Medicare payments to women physicians in 2013 were 55% of those to male physicians across all specialties.  

“It can be disheartening, especially as an early career woman cardiologist, seeing these differences, but I think the responsibility on all of us is to take these observations and really try to understand more deeply why they exist,” Nosheen Reza, MD, from the University of Pennsylvania, Philadelphia, and coauthor of the cross-sectional analysis, told this news organization.

Several factors could be contributing to the disparity, but “it’s not gender discrimination from Medicare,” Dr. Raber said. “The gap in reimbursement is really driven by the types and the volume of charges submitted.”

Indeed, a direct comparison of the three most common inpatient and outpatient billing codes showed no difference in payments between the sexes.

Men, however, submitted 24% more median inpatient charges to CMS than women (1,190 vs. 959), and 94% more outpatient charges (1,685 vs. 870).

Men also submitted slightly more unique billing codes (median inpatient, 10 vs. 9; median outpatient, 11 vs. 8).

Notably, women made up just 13% of the 17,524 cardiologists who received CMS payments in the inpatient setting in 2016 and 13% of the 16,929 cardiologists who did so in the outpatient setting.

Louisiana had the dubious distinction of having the largest gender gap in mean CMS payments, with male cardiologists earning $145,323 (235%) more than women, whereas women cardiologists in Vermont out-earned men by $31,483 (38%).

Overall, male cardiologists had more years in practice than women cardiologists and cared for slightly older Medicare beneficiaries.

Differences in CMS payments persisted, however, after adjustment for years since graduation, physician subspecialty, number of charges, number of unique billing codes, and patient complexity. The resulting β coefficient was -0.06, which translates into women receiving an average of 94% of the CMS payments received by men.

“The first takeaway, if you were really crass and focused on the bottom line, might be: ‘Hey, let me get a few more male cardiologists because they’re going to bring more into the organization.’ But we shouldn’t do that because, unless you link these data with quality outcomes, they’re an interesting observation and hypothesis-generating,” said Sharonne Hayes, MD, coauthor of the 2017 report and professor of cardiovascular medicine at Mayo Clinic in Rochester, Minn., where she has served as director of diversity and inclusion for a decade.

She noted that there are multiple examples that the style of medicine women practice, on average, may be more effective, may be more outcomes based, and may save lives, as suggested by a recent analysis of hospitalized Medicare beneficiaries.

“The gap was not much different, like within 1% or so, but when you take that over the literally millions of Medicare patients cared for each year by hospitalists, that’s a substantial number of people,” Dr. Hayes said. “So, I think we need to take a step back, and we have to include these observations on studies like this and better understand the compensation gaps.”

She pointed out that the present study lacks data on full-time-equivalent status but that female physicians are more likely to work part-time, thus reducing the volume of claims.

Women might also care for different patient populations. “I practice in a women’s heart clinic and take care of [spontaneous coronary artery dissection] SCAD patients where the average age of SCAD is 42. So, the vast majority of patients I see on a day-to-day basis aren’t going to be Medicare age,” observed Dr. Hayes.

The differences in charges might also reflect the increased obligations in nonreimbursed work that women can have, Dr. Raber said. These can be things like mentoring, teaching roles, and serving on committees, which is a hypothesis supported by a 2021 study that showed women physicians spend more time on these “citizenship tasks” than men.

Finally, there could be organizational barriers that affect women’s clinical volumes, including less access to support from health care personnel. Added support is especially important, though, amid a 100-year pandemic, the women agreed.

“Within the first year of the pandemic, we saw women leaving the workforce in droves across all sectors, including medicine, including academic medicine. And, as the pandemic goes on without any signs of abatement, those threats continue to exist and continue to be amplified,” Dr. Reza said.

The groundswell of support surrounding the importance of diversity, equity, and inclusion initiatives across the board has helped bring attention to the issue, she said. Some institutions, including the National Institutes of Health, are making efforts to extend relief to women with young families, caregivers, or those in academic medicine who, for example, need extensions on grants or bridge funding.

“There’s certainly a lot left to do, but I do think within the last year, there’s been an acceleration of literature that has come out, not only pointing out the disparities, but pointing out that perhaps women physicians do have better outcomes and are better liked by their patients and that losing women in the workforce would be a huge detriment to the field overall,” Dr. Reza said.

Dr. Raber, Dr. Reza, and Dr. Hayes reports no relevant financial relationships. Coauthor conflict of interest disclosures are listed in the paper.

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

Women cardiologists receive dramatically smaller payments from the U.S. Centers for Medicare & Medicaid Services (CMS) than their male counterparts, new research suggests.

An analysis of 2016 claims data revealed male cardiologists received on average 45% more reimbursement than women in the inpatient setting, with the median payment 39% higher ($62,897 vs. $45,288).

In the outpatient setting, men received on average 62% more annual CMS payments, with the median payment 75% higher ($91,053 vs. $51,975; P < .001 for both).

The difference remained significant after the exclusion of the top and bottom 2.5% of earning physicians and cardiology subspecialties, like electrophysiology and interventional cardiology, with high procedural volumes and greater gender imbalances.

“This is one study among others which demonstrates a wage gap between men and women in medicine in cardiology,” lead author Inbar Raber, MD, Beth Israel Deaconess Medical Center, Boston, said in an interview. “I hope by increasing awareness [and] understanding of possible etiologies, it will enable some sustainable solutions, and those include access to additional support staff and equitable models surrounding parental leave and childcare support.”

The study, published online September 8 in JAMA Cardiology, comes on the heels of a recent cross-sectional analysis that put cardiology at the bottom of 13 internal medicine subspecialties with just 21% female faculty representation and one of only three specialties in which women’s median salaries did not reach 90% of men’s.

The new findings build on a 2017 report that showed Medicare payments to women physicians in 2013 were 55% of those to male physicians across all specialties.  

“It can be disheartening, especially as an early career woman cardiologist, seeing these differences, but I think the responsibility on all of us is to take these observations and really try to understand more deeply why they exist,” Nosheen Reza, MD, from the University of Pennsylvania, Philadelphia, and coauthor of the cross-sectional analysis, told this news organization.

Several factors could be contributing to the disparity, but “it’s not gender discrimination from Medicare,” Dr. Raber said. “The gap in reimbursement is really driven by the types and the volume of charges submitted.”

Indeed, a direct comparison of the three most common inpatient and outpatient billing codes showed no difference in payments between the sexes.

Men, however, submitted 24% more median inpatient charges to CMS than women (1,190 vs. 959), and 94% more outpatient charges (1,685 vs. 870).

Men also submitted slightly more unique billing codes (median inpatient, 10 vs. 9; median outpatient, 11 vs. 8).

Notably, women made up just 13% of the 17,524 cardiologists who received CMS payments in the inpatient setting in 2016 and 13% of the 16,929 cardiologists who did so in the outpatient setting.

Louisiana had the dubious distinction of having the largest gender gap in mean CMS payments, with male cardiologists earning $145,323 (235%) more than women, whereas women cardiologists in Vermont out-earned men by $31,483 (38%).

Overall, male cardiologists had more years in practice than women cardiologists and cared for slightly older Medicare beneficiaries.

Differences in CMS payments persisted, however, after adjustment for years since graduation, physician subspecialty, number of charges, number of unique billing codes, and patient complexity. The resulting β coefficient was -0.06, which translates into women receiving an average of 94% of the CMS payments received by men.

“The first takeaway, if you were really crass and focused on the bottom line, might be: ‘Hey, let me get a few more male cardiologists because they’re going to bring more into the organization.’ But we shouldn’t do that because, unless you link these data with quality outcomes, they’re an interesting observation and hypothesis-generating,” said Sharonne Hayes, MD, coauthor of the 2017 report and professor of cardiovascular medicine at Mayo Clinic in Rochester, Minn., where she has served as director of diversity and inclusion for a decade.

She noted that there are multiple examples that the style of medicine women practice, on average, may be more effective, may be more outcomes based, and may save lives, as suggested by a recent analysis of hospitalized Medicare beneficiaries.

“The gap was not much different, like within 1% or so, but when you take that over the literally millions of Medicare patients cared for each year by hospitalists, that’s a substantial number of people,” Dr. Hayes said. “So, I think we need to take a step back, and we have to include these observations on studies like this and better understand the compensation gaps.”

She pointed out that the present study lacks data on full-time-equivalent status but that female physicians are more likely to work part-time, thus reducing the volume of claims.

Women might also care for different patient populations. “I practice in a women’s heart clinic and take care of [spontaneous coronary artery dissection] SCAD patients where the average age of SCAD is 42. So, the vast majority of patients I see on a day-to-day basis aren’t going to be Medicare age,” observed Dr. Hayes.

The differences in charges might also reflect the increased obligations in nonreimbursed work that women can have, Dr. Raber said. These can be things like mentoring, teaching roles, and serving on committees, which is a hypothesis supported by a 2021 study that showed women physicians spend more time on these “citizenship tasks” than men.

Finally, there could be organizational barriers that affect women’s clinical volumes, including less access to support from health care personnel. Added support is especially important, though, amid a 100-year pandemic, the women agreed.

“Within the first year of the pandemic, we saw women leaving the workforce in droves across all sectors, including medicine, including academic medicine. And, as the pandemic goes on without any signs of abatement, those threats continue to exist and continue to be amplified,” Dr. Reza said.

The groundswell of support surrounding the importance of diversity, equity, and inclusion initiatives across the board has helped bring attention to the issue, she said. Some institutions, including the National Institutes of Health, are making efforts to extend relief to women with young families, caregivers, or those in academic medicine who, for example, need extensions on grants or bridge funding.

“There’s certainly a lot left to do, but I do think within the last year, there’s been an acceleration of literature that has come out, not only pointing out the disparities, but pointing out that perhaps women physicians do have better outcomes and are better liked by their patients and that losing women in the workforce would be a huge detriment to the field overall,” Dr. Reza said.

Dr. Raber, Dr. Reza, and Dr. Hayes reports no relevant financial relationships. Coauthor conflict of interest disclosures are listed in the paper.

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

A new joint consensus statement by four major diabetes organizations aims to standardize the terminology, definition, and assessment to the phenomenon of diabetes “remission.”

The statement was jointly issued by the American Diabetes Association, the Endocrine Society, the European Association for the Study of Diabetes, and Diabetes UK.

The 12-member international writing panel proposed use of the term “remission,” as opposed to others such as “reversal,” “resolution,” or “cure,” to describe the phenomenon of prolonged normoglycemia without the use of glucose-lowering medication in a person previously diagnosed with type 2 diabetes.

“Diabetes remission may be occurring more often due to advances in treatment,” writing group member Amy Rothberg, MD, of the University of Michigan, Ann Arbor, said in a statement.

The group defined “remission” – whether attained via lifestyle, bariatric surgery, or other means – as an A1c < 6.5% (< 48 mmol/mol) at least 3 months after cessation of glucose-lowering pharmacotherapy. The panel also suggested monitoring individuals experiencing diabetes remission and raised questions that need further attention and study.

But it’s not a guideline, panel chair Matthew C. Riddle, MD, said in an interview. Rather, the “main purpose of the statement was to provide definitions, terminology, cut-points, and timing recommendations to allow data collection that will eventually lead to clinical guidelines,” he said.

A great deal of epidemiological research is conducted by analyzing data from medical records, he noted. “If clinicians are more consistent in entering data into the records and in doing measurements, it will be a better database.”
 

Remission reality: Advice needed for deprescribing, talking to patients

“Increasingly our treatments are getting glucose levels into the normal range, and in many cases, even after withdrawal of drug therapy. That’s not an anomaly or a fiction, it’s reality. Clinicians need to know how to talk to their patients about it,” noted Dr. Riddle, of the division of endocrinology, diabetes, and clinical nutrition at Oregon Health & Science University, Portland.

There is a need for data on the effects of deprescribing once normoglycemia is achieved, he said. “It really goes a long way to have strong epidemiological and interventional evidence. That’s what we need here, and that’s what the group is really hoping for.”

The statement recommends the following:

• The term “remission” should be used to describe a sustained metabolic improvement in type 2 diabetes to near normal levels. The panel agreed the word strikes the best balance, given that insulin resistance and beta-cell dysfunction may still be present despite normoglycemia. “Diabetes doesn’t get cured. The underlying abnormalities are still there. Remission is defined by glucose,” Dr. Riddle said. The panel also decided to do away with ADA’s former terms “partial,” “complete,” and “prolonged” remission because they are ambiguous and unhelpful. 
• Remission should be defined as a return to an A1c of < 6.5% (< 48 mmol/mol) – the threshold used to diagnose diabetes – spontaneously or following an intervention and that persists for at least 3 months in the absence of usual glucose-lowering medication.
• When A1c may be unreliable, such as conditions involving variant hemoglobin or erythrocyte survival alterations, acceptable alternatives are a fasting blood glucose < 126 mg/dL (< 7.0 mmol/L) or an estimated A1c < 6.5% calculated from continuous glucose monitoring data.
• A1c testing to document a remission should be performed just prior to an intervention and no sooner than 3 months after initiation of the intervention and withdrawal of any glucose-lowering medication.
• Subsequent ongoing A1c testing should be done at least yearly thereafter, along with routine monitoring for diabetes-related complications, including retinal screening, renal function assessment, foot exams, and cardiovascular risk factor testing. “At present, there is no long-term evidence indicating that any of the usually recommended assessments for complications can safely be discontinued,” the authors wrote.
• Research based on the terminology and definitions in the present statement is needed to determine the frequency, duration, and effects on short- and long-term medical outcomes of type 2 diabetes remissions using available interventions.

Dr. Riddle said in an interview: “We thought that the clinical community needed to understand where this issue stands right now. The feasibility of a remission is greater than it used to be.

“We’re going to see more patients who have what we can now call a remission according to a standardized definition. In the future, there are likely to be guidelines regarding the kind of patients and the kind of tactics appropriate for seeking a remission,” he said.

The statement was simultaneously published online in each of the organizations’ respective journals: Diabetes Care, Journal of Clinical Endocrinology & Metabolism, Diabetologia, and Diabetic Medicine.

Dr. Riddle has reported receiving research grant support through Oregon Health & Science University from Eli Lilly, Novo Nordisk, and AstraZeneca and honoraria for consulting from Adocia, Intercept, and Theracos.

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

A new joint consensus statement by four major diabetes organizations aims to standardize the terminology, definition, and assessment to the phenomenon of diabetes “remission.”

The statement was jointly issued by the American Diabetes Association, the Endocrine Society, the European Association for the Study of Diabetes, and Diabetes UK.

The 12-member international writing panel proposed use of the term “remission,” as opposed to others such as “reversal,” “resolution,” or “cure,” to describe the phenomenon of prolonged normoglycemia without the use of glucose-lowering medication in a person previously diagnosed with type 2 diabetes.

“Diabetes remission may be occurring more often due to advances in treatment,” writing group member Amy Rothberg, MD, of the University of Michigan, Ann Arbor, said in a statement.

The group defined “remission” – whether attained via lifestyle, bariatric surgery, or other means – as an A1c < 6.5% (< 48 mmol/mol) at least 3 months after cessation of glucose-lowering pharmacotherapy. The panel also suggested monitoring individuals experiencing diabetes remission and raised questions that need further attention and study.

But it’s not a guideline, panel chair Matthew C. Riddle, MD, said in an interview. Rather, the “main purpose of the statement was to provide definitions, terminology, cut-points, and timing recommendations to allow data collection that will eventually lead to clinical guidelines,” he said.

A great deal of epidemiological research is conducted by analyzing data from medical records, he noted. “If clinicians are more consistent in entering data into the records and in doing measurements, it will be a better database.”
 

Remission reality: Advice needed for deprescribing, talking to patients

“Increasingly our treatments are getting glucose levels into the normal range, and in many cases, even after withdrawal of drug therapy. That’s not an anomaly or a fiction, it’s reality. Clinicians need to know how to talk to their patients about it,” noted Dr. Riddle, of the division of endocrinology, diabetes, and clinical nutrition at Oregon Health & Science University, Portland.

There is a need for data on the effects of deprescribing once normoglycemia is achieved, he said. “It really goes a long way to have strong epidemiological and interventional evidence. That’s what we need here, and that’s what the group is really hoping for.”

The statement recommends the following:

• The term “remission” should be used to describe a sustained metabolic improvement in type 2 diabetes to near normal levels. The panel agreed the word strikes the best balance, given that insulin resistance and beta-cell dysfunction may still be present despite normoglycemia. “Diabetes doesn’t get cured. The underlying abnormalities are still there. Remission is defined by glucose,” Dr. Riddle said. The panel also decided to do away with ADA’s former terms “partial,” “complete,” and “prolonged” remission because they are ambiguous and unhelpful. 
• Remission should be defined as a return to an A1c of < 6.5% (< 48 mmol/mol) – the threshold used to diagnose diabetes – spontaneously or following an intervention and that persists for at least 3 months in the absence of usual glucose-lowering medication.
• When A1c may be unreliable, such as conditions involving variant hemoglobin or erythrocyte survival alterations, acceptable alternatives are a fasting blood glucose < 126 mg/dL (< 7.0 mmol/L) or an estimated A1c < 6.5% calculated from continuous glucose monitoring data.
• A1c testing to document a remission should be performed just prior to an intervention and no sooner than 3 months after initiation of the intervention and withdrawal of any glucose-lowering medication.
• Subsequent ongoing A1c testing should be done at least yearly thereafter, along with routine monitoring for diabetes-related complications, including retinal screening, renal function assessment, foot exams, and cardiovascular risk factor testing. “At present, there is no long-term evidence indicating that any of the usually recommended assessments for complications can safely be discontinued,” the authors wrote.
• Research based on the terminology and definitions in the present statement is needed to determine the frequency, duration, and effects on short- and long-term medical outcomes of type 2 diabetes remissions using available interventions.

Dr. Riddle said in an interview: “We thought that the clinical community needed to understand where this issue stands right now. The feasibility of a remission is greater than it used to be.

“We’re going to see more patients who have what we can now call a remission according to a standardized definition. In the future, there are likely to be guidelines regarding the kind of patients and the kind of tactics appropriate for seeking a remission,” he said.

The statement was simultaneously published online in each of the organizations’ respective journals: Diabetes Care, Journal of Clinical Endocrinology & Metabolism, Diabetologia, and Diabetic Medicine.

Dr. Riddle has reported receiving research grant support through Oregon Health & Science University from Eli Lilly, Novo Nordisk, and AstraZeneca and honoraria for consulting from Adocia, Intercept, and Theracos.

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

A new joint consensus statement by four major diabetes organizations aims to standardize the terminology, definition, and assessment to the phenomenon of diabetes “remission.”

The statement was jointly issued by the American Diabetes Association, the Endocrine Society, the European Association for the Study of Diabetes, and Diabetes UK.

The 12-member international writing panel proposed use of the term “remission,” as opposed to others such as “reversal,” “resolution,” or “cure,” to describe the phenomenon of prolonged normoglycemia without the use of glucose-lowering medication in a person previously diagnosed with type 2 diabetes.

“Diabetes remission may be occurring more often due to advances in treatment,” writing group member Amy Rothberg, MD, of the University of Michigan, Ann Arbor, said in a statement.

The group defined “remission” – whether attained via lifestyle, bariatric surgery, or other means – as an A1c < 6.5% (< 48 mmol/mol) at least 3 months after cessation of glucose-lowering pharmacotherapy. The panel also suggested monitoring individuals experiencing diabetes remission and raised questions that need further attention and study.

But it’s not a guideline, panel chair Matthew C. Riddle, MD, said in an interview. Rather, the “main purpose of the statement was to provide definitions, terminology, cut-points, and timing recommendations to allow data collection that will eventually lead to clinical guidelines,” he said.

A great deal of epidemiological research is conducted by analyzing data from medical records, he noted. “If clinicians are more consistent in entering data into the records and in doing measurements, it will be a better database.”
 

Remission reality: Advice needed for deprescribing, talking to patients

“Increasingly our treatments are getting glucose levels into the normal range, and in many cases, even after withdrawal of drug therapy. That’s not an anomaly or a fiction, it’s reality. Clinicians need to know how to talk to their patients about it,” noted Dr. Riddle, of the division of endocrinology, diabetes, and clinical nutrition at Oregon Health & Science University, Portland.

There is a need for data on the effects of deprescribing once normoglycemia is achieved, he said. “It really goes a long way to have strong epidemiological and interventional evidence. That’s what we need here, and that’s what the group is really hoping for.”

The statement recommends the following:

• The term “remission” should be used to describe a sustained metabolic improvement in type 2 diabetes to near normal levels. The panel agreed the word strikes the best balance, given that insulin resistance and beta-cell dysfunction may still be present despite normoglycemia. “Diabetes doesn’t get cured. The underlying abnormalities are still there. Remission is defined by glucose,” Dr. Riddle said. The panel also decided to do away with ADA’s former terms “partial,” “complete,” and “prolonged” remission because they are ambiguous and unhelpful. 
• Remission should be defined as a return to an A1c of < 6.5% (< 48 mmol/mol) – the threshold used to diagnose diabetes – spontaneously or following an intervention and that persists for at least 3 months in the absence of usual glucose-lowering medication.
• When A1c may be unreliable, such as conditions involving variant hemoglobin or erythrocyte survival alterations, acceptable alternatives are a fasting blood glucose < 126 mg/dL (< 7.0 mmol/L) or an estimated A1c < 6.5% calculated from continuous glucose monitoring data.
• A1c testing to document a remission should be performed just prior to an intervention and no sooner than 3 months after initiation of the intervention and withdrawal of any glucose-lowering medication.
• Subsequent ongoing A1c testing should be done at least yearly thereafter, along with routine monitoring for diabetes-related complications, including retinal screening, renal function assessment, foot exams, and cardiovascular risk factor testing. “At present, there is no long-term evidence indicating that any of the usually recommended assessments for complications can safely be discontinued,” the authors wrote.
• Research based on the terminology and definitions in the present statement is needed to determine the frequency, duration, and effects on short- and long-term medical outcomes of type 2 diabetes remissions using available interventions.

Dr. Riddle said in an interview: “We thought that the clinical community needed to understand where this issue stands right now. The feasibility of a remission is greater than it used to be.

“We’re going to see more patients who have what we can now call a remission according to a standardized definition. In the future, there are likely to be guidelines regarding the kind of patients and the kind of tactics appropriate for seeking a remission,” he said.

The statement was simultaneously published online in each of the organizations’ respective journals: Diabetes Care, Journal of Clinical Endocrinology & Metabolism, Diabetologia, and Diabetic Medicine.

Dr. Riddle has reported receiving research grant support through Oregon Health & Science University from Eli Lilly, Novo Nordisk, and AstraZeneca and honoraria for consulting from Adocia, Intercept, and Theracos.

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

The anti-inflammatory agents colchicine and icosapent ethyl (Vascepa; Amarin) failed to provide substantial benefits in separate randomized COVID-19 trials.

Both were reported at the European Society of Cardiology (ESC) Congress 2021.

The open-label ECLA PHRI COLCOVID trial randomized 1,277 hospitalized adults (mean age 62 years) to usual care alone or with colchicine at a loading dose of 1.5 mg for 2 hours followed by 0.5 mg on day 1 and then 0.5 mg twice daily for 14 days or until discharge.

The investigators hypothesized that colchicine, which is widely used to treat gout and other inflammatory conditions, might modulate the hyperinflammatory syndrome, or cytokine storm, associated with COVID-19.

Results showed that the need for mechanical ventilation or death occurred in 25.0% of patients receiving colchicine and 28.8% with usual care (P = .08).

The coprimary endpoint of death at 28 days was also not significantly different between groups (20.5% vs. 22.2%), principal investigator Rafael Diaz, MD, said in a late-breaking COVID-19 trials session at the congress.

Among the secondary outcomes at 28 days, colchicine significantly reduced the incidence of new intubation or death from respiratory failure from 27.0% to 22.3% (hazard ratio, 0.79; 95% confidence interval, 0.63-0.99) but not mortality from respiratory failure (19.5% vs. 16.8%).

The only important adverse effect was severe diarrhea, which was reported in 11.3% of the colchicine group vs. 4.5% in the control group, said Dr. Diaz, director of Estudios Clínicos Latinoamérica (ECLA), Rosario, Argentina.

The results are consistent with those from the massive RECOVERY trial, which earlier this year stopped enrollment in the colchicine arm for lack of efficacy in patients hospitalized with COVID-19, and COLCORONA, which missed its primary endpoint using colchicine among nonhospitalized adults with COVID-19.

Session chair and COLCORONA principal investigator Jean-Claude Tardif, MD, pointed out that, as clinicians, it’s fairly uncommon to combine systemic steroids with colchicine, which was the case in 92% of patients in ECLA PHRI COLCOVID.

“I think it is an inherent limitation of testing colchicine on top of steroids,” said Dr. Tardif, of the Montreal Heart Institute.
 

Icosapent ethyl in PREPARE-IT

Dr. Diaz returned in the ESC session to present the results of the PREPARE-IT trial, which tested whether icosapent ethyl – at a loading dose of 8 grams (4 capsules) for the first 3 days and 4 g/d on days 4-60 – could reduce the risk for SARS-CoV-2 infection in 2,041 health care and other public workers in Argentina at high risk for infection (mean age 40.5 years).

Vascepa was approved by the Food and Drug Administration in 2012 for the reduction of elevated triglyceride levels, with an added indication in 2019 to reduce cardiovascular (CV) events in people with elevated triglycerides and established CV disease or diabetes with other CV risk factors.

The rationale for using the high-dose prescription eicosapentaenoic acid (EPA) preparation includes its anti-inflammatory and antithrombotic effects, and that unsaturated fatty acids, especially EPA, might inactivate the enveloped virus, he explained.

Among 1,712 participants followed for up to 60 days, however, the SARS-CoV-2 infection rate was 7.9% with icosapent ethyl vs. 7.1% with a mineral oil placebo (P = .58).

There were also no significant changes from baseline in the icosapent ethyl and placebo groups for the secondary outcomes of high-sensitivity C-reactive protein (0 vs. 0), triglycerides (median –2 mg/dL vs. 7 mg/dL), or Influenza Patient-Reported Outcome (FLU-PRO) questionnaire scores (median 0.01 vs. 0.03).

The use of a mineral oil placebo has been the subject of controversy in previous fish oil trials, but, Dr. Diaz noted, it did not have a significant proinflammatory effect or cause any excess adverse events.

Overall, adverse events were similar between the active and placebo groups, including atrial fibrillation (none), major bleeding (none), minor bleeding (7 events vs. 10 events), gastrointestinal symptoms (6.8% vs. 7.0%), and diarrhea (8.6% vs. 7.7%).

Although it missed the primary endpoint, Dr. Diaz said, “this is the first large, randomized blinded trial to demonstrate excellent safety and tolerability of an 8-gram-per-day loading dose of icosapent ethyl, opening up the potential for acute use in randomized trials of myocardial infarction, acute coronary syndromes, strokes, and revascularization.”

During a discussion of the results, Dr. Diaz said the Delta variant was not present at the time of the analysis and that the second half of the trial will report on whether icosapent ethyl can reduce the risk for hospitalization or death in participants diagnosed with COVID-19.

ECLA PHRI COLCOVID was supported by the Estudios Clínicos Latinoamérica Population Health Research Institute. PREPARE-IT was supported by Estudios Clínicos Latinoamérica with collaboration from Amarin. Dr. Diaz reports no relevant financial relationships.

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

The anti-inflammatory agents colchicine and icosapent ethyl (Vascepa; Amarin) failed to provide substantial benefits in separate randomized COVID-19 trials.

Both were reported at the European Society of Cardiology (ESC) Congress 2021.

The open-label ECLA PHRI COLCOVID trial randomized 1,277 hospitalized adults (mean age 62 years) to usual care alone or with colchicine at a loading dose of 1.5 mg for 2 hours followed by 0.5 mg on day 1 and then 0.5 mg twice daily for 14 days or until discharge.

The investigators hypothesized that colchicine, which is widely used to treat gout and other inflammatory conditions, might modulate the hyperinflammatory syndrome, or cytokine storm, associated with COVID-19.

Results showed that the need for mechanical ventilation or death occurred in 25.0% of patients receiving colchicine and 28.8% with usual care (P = .08).

The coprimary endpoint of death at 28 days was also not significantly different between groups (20.5% vs. 22.2%), principal investigator Rafael Diaz, MD, said in a late-breaking COVID-19 trials session at the congress.

Among the secondary outcomes at 28 days, colchicine significantly reduced the incidence of new intubation or death from respiratory failure from 27.0% to 22.3% (hazard ratio, 0.79; 95% confidence interval, 0.63-0.99) but not mortality from respiratory failure (19.5% vs. 16.8%).

The only important adverse effect was severe diarrhea, which was reported in 11.3% of the colchicine group vs. 4.5% in the control group, said Dr. Diaz, director of Estudios Clínicos Latinoamérica (ECLA), Rosario, Argentina.

The results are consistent with those from the massive RECOVERY trial, which earlier this year stopped enrollment in the colchicine arm for lack of efficacy in patients hospitalized with COVID-19, and COLCORONA, which missed its primary endpoint using colchicine among nonhospitalized adults with COVID-19.

Session chair and COLCORONA principal investigator Jean-Claude Tardif, MD, pointed out that, as clinicians, it’s fairly uncommon to combine systemic steroids with colchicine, which was the case in 92% of patients in ECLA PHRI COLCOVID.

“I think it is an inherent limitation of testing colchicine on top of steroids,” said Dr. Tardif, of the Montreal Heart Institute.
 

Icosapent ethyl in PREPARE-IT

Dr. Diaz returned in the ESC session to present the results of the PREPARE-IT trial, which tested whether icosapent ethyl – at a loading dose of 8 grams (4 capsules) for the first 3 days and 4 g/d on days 4-60 – could reduce the risk for SARS-CoV-2 infection in 2,041 health care and other public workers in Argentina at high risk for infection (mean age 40.5 years).

Vascepa was approved by the Food and Drug Administration in 2012 for the reduction of elevated triglyceride levels, with an added indication in 2019 to reduce cardiovascular (CV) events in people with elevated triglycerides and established CV disease or diabetes with other CV risk factors.

The rationale for using the high-dose prescription eicosapentaenoic acid (EPA) preparation includes its anti-inflammatory and antithrombotic effects, and that unsaturated fatty acids, especially EPA, might inactivate the enveloped virus, he explained.

Among 1,712 participants followed for up to 60 days, however, the SARS-CoV-2 infection rate was 7.9% with icosapent ethyl vs. 7.1% with a mineral oil placebo (P = .58).

There were also no significant changes from baseline in the icosapent ethyl and placebo groups for the secondary outcomes of high-sensitivity C-reactive protein (0 vs. 0), triglycerides (median –2 mg/dL vs. 7 mg/dL), or Influenza Patient-Reported Outcome (FLU-PRO) questionnaire scores (median 0.01 vs. 0.03).

The use of a mineral oil placebo has been the subject of controversy in previous fish oil trials, but, Dr. Diaz noted, it did not have a significant proinflammatory effect or cause any excess adverse events.

Overall, adverse events were similar between the active and placebo groups, including atrial fibrillation (none), major bleeding (none), minor bleeding (7 events vs. 10 events), gastrointestinal symptoms (6.8% vs. 7.0%), and diarrhea (8.6% vs. 7.7%).

Although it missed the primary endpoint, Dr. Diaz said, “this is the first large, randomized blinded trial to demonstrate excellent safety and tolerability of an 8-gram-per-day loading dose of icosapent ethyl, opening up the potential for acute use in randomized trials of myocardial infarction, acute coronary syndromes, strokes, and revascularization.”

During a discussion of the results, Dr. Diaz said the Delta variant was not present at the time of the analysis and that the second half of the trial will report on whether icosapent ethyl can reduce the risk for hospitalization or death in participants diagnosed with COVID-19.

ECLA PHRI COLCOVID was supported by the Estudios Clínicos Latinoamérica Population Health Research Institute. PREPARE-IT was supported by Estudios Clínicos Latinoamérica with collaboration from Amarin. Dr. Diaz reports no relevant financial relationships.

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

The anti-inflammatory agents colchicine and icosapent ethyl (Vascepa; Amarin) failed to provide substantial benefits in separate randomized COVID-19 trials.

Both were reported at the European Society of Cardiology (ESC) Congress 2021.

The open-label ECLA PHRI COLCOVID trial randomized 1,277 hospitalized adults (mean age 62 years) to usual care alone or with colchicine at a loading dose of 1.5 mg for 2 hours followed by 0.5 mg on day 1 and then 0.5 mg twice daily for 14 days or until discharge.

The investigators hypothesized that colchicine, which is widely used to treat gout and other inflammatory conditions, might modulate the hyperinflammatory syndrome, or cytokine storm, associated with COVID-19.

Results showed that the need for mechanical ventilation or death occurred in 25.0% of patients receiving colchicine and 28.8% with usual care (P = .08).

The coprimary endpoint of death at 28 days was also not significantly different between groups (20.5% vs. 22.2%), principal investigator Rafael Diaz, MD, said in a late-breaking COVID-19 trials session at the congress.

Among the secondary outcomes at 28 days, colchicine significantly reduced the incidence of new intubation or death from respiratory failure from 27.0% to 22.3% (hazard ratio, 0.79; 95% confidence interval, 0.63-0.99) but not mortality from respiratory failure (19.5% vs. 16.8%).

The only important adverse effect was severe diarrhea, which was reported in 11.3% of the colchicine group vs. 4.5% in the control group, said Dr. Diaz, director of Estudios Clínicos Latinoamérica (ECLA), Rosario, Argentina.

The results are consistent with those from the massive RECOVERY trial, which earlier this year stopped enrollment in the colchicine arm for lack of efficacy in patients hospitalized with COVID-19, and COLCORONA, which missed its primary endpoint using colchicine among nonhospitalized adults with COVID-19.

Session chair and COLCORONA principal investigator Jean-Claude Tardif, MD, pointed out that, as clinicians, it’s fairly uncommon to combine systemic steroids with colchicine, which was the case in 92% of patients in ECLA PHRI COLCOVID.

“I think it is an inherent limitation of testing colchicine on top of steroids,” said Dr. Tardif, of the Montreal Heart Institute.
 

Icosapent ethyl in PREPARE-IT

Dr. Diaz returned in the ESC session to present the results of the PREPARE-IT trial, which tested whether icosapent ethyl – at a loading dose of 8 grams (4 capsules) for the first 3 days and 4 g/d on days 4-60 – could reduce the risk for SARS-CoV-2 infection in 2,041 health care and other public workers in Argentina at high risk for infection (mean age 40.5 years).

Vascepa was approved by the Food and Drug Administration in 2012 for the reduction of elevated triglyceride levels, with an added indication in 2019 to reduce cardiovascular (CV) events in people with elevated triglycerides and established CV disease or diabetes with other CV risk factors.

The rationale for using the high-dose prescription eicosapentaenoic acid (EPA) preparation includes its anti-inflammatory and antithrombotic effects, and that unsaturated fatty acids, especially EPA, might inactivate the enveloped virus, he explained.

Among 1,712 participants followed for up to 60 days, however, the SARS-CoV-2 infection rate was 7.9% with icosapent ethyl vs. 7.1% with a mineral oil placebo (P = .58).

There were also no significant changes from baseline in the icosapent ethyl and placebo groups for the secondary outcomes of high-sensitivity C-reactive protein (0 vs. 0), triglycerides (median –2 mg/dL vs. 7 mg/dL), or Influenza Patient-Reported Outcome (FLU-PRO) questionnaire scores (median 0.01 vs. 0.03).

The use of a mineral oil placebo has been the subject of controversy in previous fish oil trials, but, Dr. Diaz noted, it did not have a significant proinflammatory effect or cause any excess adverse events.

Overall, adverse events were similar between the active and placebo groups, including atrial fibrillation (none), major bleeding (none), minor bleeding (7 events vs. 10 events), gastrointestinal symptoms (6.8% vs. 7.0%), and diarrhea (8.6% vs. 7.7%).

Although it missed the primary endpoint, Dr. Diaz said, “this is the first large, randomized blinded trial to demonstrate excellent safety and tolerability of an 8-gram-per-day loading dose of icosapent ethyl, opening up the potential for acute use in randomized trials of myocardial infarction, acute coronary syndromes, strokes, and revascularization.”

During a discussion of the results, Dr. Diaz said the Delta variant was not present at the time of the analysis and that the second half of the trial will report on whether icosapent ethyl can reduce the risk for hospitalization or death in participants diagnosed with COVID-19.

ECLA PHRI COLCOVID was supported by the Estudios Clínicos Latinoamérica Population Health Research Institute. PREPARE-IT was supported by Estudios Clínicos Latinoamérica with collaboration from Amarin. Dr. Diaz reports no relevant financial relationships.

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

Not sure if you’ve heard the news, but eating a single hot dog will apparently cost you 36 minutes of healthy life. My first thought when hearing this was of course the same as everyone else’s: Poor Joey Chestnut, multiyear winner of Nathan’s annual hot dog–eating contest.

He won this year’s contest with 76 hot dogs, which puts his total number of competition-consumed hot dogs at 1,089 – which cost him, it would seem, 27.2 days of healthy life. Unless, of course, every hot dog he inhaled came with a bun hosting two portions of sesame seeds, which in turn would buy him 50 extra minutes of life (25 minutes per portion, you see) and would consequently have extended his life by 10.6 days.

Clearly, the obvious solution here is to ensure that all hot dog buns have two portions of sesame seeds on them moving forward; that way, hot dogs can transition from being poisonous killers to antiaging medicine.

The other solution, albeit less exciting, perhaps, is for researchers to stop studying single foods’ impacts on health, and/or for journals to stop publishing them, and/or for the media to stop promoting them – because they are all as ridiculously useless as the example above highlighting findings from a newly published study in Nature Food, entitled “Small targeted dietary changes can yield substantial gains for human health and the environment.”

While no doubt we would all love for diet and health to be so well understood that we could choose specific single foods (knowing that they would prolong our lives) while avoiding single foods that would shorten it, there’s this unfortunate truth that the degree of confounding among food alone is staggering. People eat thousands of different foods in thousands of different dietary combinations. Moreover, most (all?) research conducted on dietary impacts of single foods on health don’t actually track consumption of those specific foods over time, let alone their interactions with all other foods consumed, but rather at moments in time.

In the case of the “hot dogs will kill you unless there are sesame seeds on your bun” article, for example, the researchers utilized one solitary dietary recall session upon which to base their ridiculously specific, ridiculous conclusions.

People’s diets also change over time for various reasons, and of course people themselves are very different. You might imagine that people whose diets are rich in chicken wings, sugared soda, and hot dogs will have markedly different lifestyles and demographics than those whose diets are rich in walnuts, sashimi, and avocados.

So why do we keep seeing studies like this being published? Is it because they’re basically clickbait catnip for journals and newspapers, and in our publish-or-perish attention-seeking world, that means they not only get a pass but they get a press release? Is it because peer review is broken and everyone knows it? Is it because as a society, we’re frogs who have been steeping for decades in the ever-heated pot of nutritional nonsense, and consequently don’t think to question it?

I don’t know the answer to any of those questions, but one thing I do know: Studies on single foods’ impact on life length are pointless, impossible, and idiotic, and people who share them noncritically should be forever shunned – or at the very least, forever ignored.

Yoni Freedhoff, MD, is an associate professor of family medicine at the University of Ottawa and medical director of the Bariatric Medical Institute, a nonsurgical weight-management center.

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

Not sure if you’ve heard the news, but eating a single hot dog will apparently cost you 36 minutes of healthy life. My first thought when hearing this was of course the same as everyone else’s: Poor Joey Chestnut, multiyear winner of Nathan’s annual hot dog–eating contest.

He won this year’s contest with 76 hot dogs, which puts his total number of competition-consumed hot dogs at 1,089 – which cost him, it would seem, 27.2 days of healthy life. Unless, of course, every hot dog he inhaled came with a bun hosting two portions of sesame seeds, which in turn would buy him 50 extra minutes of life (25 minutes per portion, you see) and would consequently have extended his life by 10.6 days.

Clearly, the obvious solution here is to ensure that all hot dog buns have two portions of sesame seeds on them moving forward; that way, hot dogs can transition from being poisonous killers to antiaging medicine.

The other solution, albeit less exciting, perhaps, is for researchers to stop studying single foods’ impacts on health, and/or for journals to stop publishing them, and/or for the media to stop promoting them – because they are all as ridiculously useless as the example above highlighting findings from a newly published study in Nature Food, entitled “Small targeted dietary changes can yield substantial gains for human health and the environment.”

While no doubt we would all love for diet and health to be so well understood that we could choose specific single foods (knowing that they would prolong our lives) while avoiding single foods that would shorten it, there’s this unfortunate truth that the degree of confounding among food alone is staggering. People eat thousands of different foods in thousands of different dietary combinations. Moreover, most (all?) research conducted on dietary impacts of single foods on health don’t actually track consumption of those specific foods over time, let alone their interactions with all other foods consumed, but rather at moments in time.

In the case of the “hot dogs will kill you unless there are sesame seeds on your bun” article, for example, the researchers utilized one solitary dietary recall session upon which to base their ridiculously specific, ridiculous conclusions.

People’s diets also change over time for various reasons, and of course people themselves are very different. You might imagine that people whose diets are rich in chicken wings, sugared soda, and hot dogs will have markedly different lifestyles and demographics than those whose diets are rich in walnuts, sashimi, and avocados.

So why do we keep seeing studies like this being published? Is it because they’re basically clickbait catnip for journals and newspapers, and in our publish-or-perish attention-seeking world, that means they not only get a pass but they get a press release? Is it because peer review is broken and everyone knows it? Is it because as a society, we’re frogs who have been steeping for decades in the ever-heated pot of nutritional nonsense, and consequently don’t think to question it?

I don’t know the answer to any of those questions, but one thing I do know: Studies on single foods’ impact on life length are pointless, impossible, and idiotic, and people who share them noncritically should be forever shunned – or at the very least, forever ignored.

Yoni Freedhoff, MD, is an associate professor of family medicine at the University of Ottawa and medical director of the Bariatric Medical Institute, a nonsurgical weight-management center.

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

Not sure if you’ve heard the news, but eating a single hot dog will apparently cost you 36 minutes of healthy life. My first thought when hearing this was of course the same as everyone else’s: Poor Joey Chestnut, multiyear winner of Nathan’s annual hot dog–eating contest.

He won this year’s contest with 76 hot dogs, which puts his total number of competition-consumed hot dogs at 1,089 – which cost him, it would seem, 27.2 days of healthy life. Unless, of course, every hot dog he inhaled came with a bun hosting two portions of sesame seeds, which in turn would buy him 50 extra minutes of life (25 minutes per portion, you see) and would consequently have extended his life by 10.6 days.

Clearly, the obvious solution here is to ensure that all hot dog buns have two portions of sesame seeds on them moving forward; that way, hot dogs can transition from being poisonous killers to antiaging medicine.

The other solution, albeit less exciting, perhaps, is for researchers to stop studying single foods’ impacts on health, and/or for journals to stop publishing them, and/or for the media to stop promoting them – because they are all as ridiculously useless as the example above highlighting findings from a newly published study in Nature Food, entitled “Small targeted dietary changes can yield substantial gains for human health and the environment.”

While no doubt we would all love for diet and health to be so well understood that we could choose specific single foods (knowing that they would prolong our lives) while avoiding single foods that would shorten it, there’s this unfortunate truth that the degree of confounding among food alone is staggering. People eat thousands of different foods in thousands of different dietary combinations. Moreover, most (all?) research conducted on dietary impacts of single foods on health don’t actually track consumption of those specific foods over time, let alone their interactions with all other foods consumed, but rather at moments in time.

In the case of the “hot dogs will kill you unless there are sesame seeds on your bun” article, for example, the researchers utilized one solitary dietary recall session upon which to base their ridiculously specific, ridiculous conclusions.

People’s diets also change over time for various reasons, and of course people themselves are very different. You might imagine that people whose diets are rich in chicken wings, sugared soda, and hot dogs will have markedly different lifestyles and demographics than those whose diets are rich in walnuts, sashimi, and avocados.

So why do we keep seeing studies like this being published? Is it because they’re basically clickbait catnip for journals and newspapers, and in our publish-or-perish attention-seeking world, that means they not only get a pass but they get a press release? Is it because peer review is broken and everyone knows it? Is it because as a society, we’re frogs who have been steeping for decades in the ever-heated pot of nutritional nonsense, and consequently don’t think to question it?

I don’t know the answer to any of those questions, but one thing I do know: Studies on single foods’ impact on life length are pointless, impossible, and idiotic, and people who share them noncritically should be forever shunned – or at the very least, forever ignored.

Yoni Freedhoff, MD, is an associate professor of family medicine at the University of Ottawa and medical director of the Bariatric Medical Institute, a nonsurgical weight-management center.

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

The featured report from the 6,000-patient EMPEROR-Preserved trial at the virtual annual congress of the European Society of Cardiology drew lots of attention for its headline finding: the first unequivocal demonstration that a medication, empagliflozin, can significantly reduce the rate of cardiovascular death and hospitalization for heart failure in patients with heart failure with preserved ejection fraction (HFpEF, a left ventricular ejection fraction of more than 40%), with the details simultaneously published online.

But at the same time, the EMPEROR-Preserved investigators released four additional reports with a lot more outcome analyses that also deserve some attention.
 

The puzzling neutral effect on renal events

Perhaps the most surprising and complicated set of findings among the main EMPEROR-Preserved outcomes involved renal outcomes.

The trial’s primary outcome was the combined rate of cardiovascular death or hospitalization for heart failure (HHF), and the results showed that treatment with empagliflozin (Jardiance) for a median of 26 months on top of standard treatment for patients with HFpEF led to a significant 21% relative risk reduction, compared with placebo-treated patients.

The trial had two prespecified secondary outcomes. One was the total number of HHF, which dropped by a significant 27%, compared with placebo. The second was the mean change in slope of estimated glomerular filtration rate (eGFR) on an annualized basis, and the empagliflozin regimen reduced the cumulative annual deficit, compared with placebo by an average of 1.36 mL/min per 1.73 m^2, a significant difference.

This preservation of renal function was consistent with results from many prior studies of empagliflozin and all of the other U.S.-approved agents from the sodium-glucose cotransporter 2 inhibitor class. Preservation of renal function and a reduction in renal events has become a hallmark property of all agents in the SGLT2 inhibitor class both in patients with type 2 diabetes, as well as in those without diabetes but with heart failure with reduced ejection fraction (HFrEF) or with chronic kidney disease.

EMPEROR-Preserved threw a wrench into what had been an unbroken history of renal protection by SGLT2 inhibitors. That happened when a prespecified endpoint of the study – a composite renal outcome defined as time to first occurrence of chronic dialysis, renal transplantation, a sustained reduction of at least 40% in eGFR, or a sustained drop in eGFR of more than 10 or 15 mL/min per 1.73 m2 from baseline – yielded an unexpected neutral finding.

For this composite renal outcome, EMPEROR-Preserved showed a nonsignificant 5% reduction, compared with placebo, a result that both differed from what had been seen in essentially all the other SGLT2 inhibitor trials that had looked at this, but which also seemed at odds with the observed significant preservation of renal function that seemed substantial enough to produce a clinically meaningful benefit.
 

Renal effects blunted in HFpEF

The immediate upshot was a letter published by several EMPEROR-Preserved investigators that spelled out this discrepancy and came to the jolting conclusion that “eGFR slope analysis has limitations as a surrogate for predicting the effect of drugs on renal outcomes in patients with heart failure.”

The same authors, along with some additional associates, also published a second letter that noted a further unexpected twist with the renal outcome: “In prior large-scale clinical trials, the effect of SGLT2 inhibitors on heart failure and renal outcomes had consistently tracked together,” they noted, but in this case it didn’t, a discordance they said was “extraordinarily puzzling”.

MDedge News

This led the study’s leaders to reanalyze the renal outcomes using a different definition, one that Milton Packer, MD, who helped design the trial and oversaw several of its analyses, called “a more conventional definition of renal events,” during his presentation of these findings at the congress. The researchers swapped out a 40% drop from baseline eGFR as an event and replaced it with a 50% decline, a change designed to screen out less severe, and often transient, reductions in kidney function that have less lasting impact on health. They also added an additional component to the composite endpoint, renal death. A revised analysis using this new renal composite outcome appeared in the European Journal of Heart Failure letter.

This change cut the total number of renal events tallied in the trial nearly in half, down to 112, and showed a more robust decline in renal events with empagliflozin treatment compared with the initial analysis, although the drop remained nonsignificant. The revised analysis also showed that the overall, nonsignificant 22% relative reduction in renal events in patients on empagliflozin, compared with placebo, dwindled down to completely nonexistent in the tertile of patients with a left ventricular ejection fraction of 60% or greater. In this tertile the hazard ratio actually showed a nonsignificant point estimate of a 24% increased rate of renal events on empagliflozin, with the caveat that this subgroup now included a total of just 40 total events between the two treatment arms. (Each of the two other tertiles also had roughly the same number of total events.)

The biggest effect on renal-event reduction was in the tertile of patients with an ejection fraction of 41%-49%, in which empagliflozin treatment was linked with a significant 59% cut in renal events, compared with placebo. The analysis also showed significant heterogeneity in thus outcome between this subgroup and the other two tertiles that had higher ejection fractions and showed reduced rates of protection by empagliflozin against renal events.

This apparent blunting of a renal effect despite preservation of renal function seemed to mimic the blunting of the primary cardiovascular outcome effect that also appeared in patients with ejection fractions in the 60%-65% range or above.

“If we knew what blunted the effect of empagliflozin on heart failure outcomes at higher ejection fraction levels, we think the same explanation may also apply to the blunting of effect on renal outcomes, but right now we do not know the answer to either question,” Dr. Packer said in an interview. He’s suggested that one possibility is that many of the enrolled patients identified as having HFpEF, but with these high ejection fractions may have not actually had HFpEF, and their signs and symptoms may have instead resulted from atrial fibrillation.

“Many patients with an ejection fraction of 60%-65% and above had atrial fibrillation,” he noted, with a prevalence at enrollment in this subgroup of about 50%. Atrial fibrillation can cause dyspnea, a hallmark symptom leading to diagnosis of heart failure, and it also increases levels of N-terminal of the prohormone brain natriuretic peptide, a metric that served as a gatekeeper for entry into the trial. “Essentially, we are saying that many of the criteria that we specified to ensure that patients had heart failure probably did not work very well in patients with an ejection fraction of 65% or greater,” said Dr. Packer, a cardiologist at Baylor University Medical Center in Dallas. “We need to figure out who these patients are.”

Some experts not involved with the study voiced skepticism that the renal findings reflected a real issue.

“I’m quite optimistic that in the long-term the effect on eGFR will translate into renal protection,” said Rudolf A. de Boer, MD, PhD, a professor of translational cardiology at University Medical Center Groningen (the Netherlands), and designated discussant at the congress for the presentation by Dr. Packer.

Catherine Hackett/MDedge News

John J.V. McMurray, MD, a professor of cardiology and a heart failure specialist at Glasgow University, speculated that the unexpected renal outcomes data may relate to the initial decline in renal function produced by treatment with SGLT2 inhibitors despite their longer-term enhancement of renal protection.

“If you use a treatment that protects the kidneys in the long-term but causes an initial dip in eGFR, more patients receiving that treatment will have an early ‘event,’ ” he noted in an interview. He also cautioned about the dangers of subgroup analyses that dice the study population into small cohorts.

“Trials are powered to look at the effect of treatment in the overall population. Everything else is exploratory, underpowered, and subject to the play of chance,” Dr. McMurray stressed.
 

Counting additional cardiovascular disease events allows more analyses

A third auxiliary report from the EMPEROR-Preserved investigators performed several prespecified analyses that depended on adding additional cardiovascular disease endpoints to the core tallies of cardiovascular death or HHF – such as emergent, urgent, and outpatient events that reflected worsening heart failure – and also included information on diuretic and vasopressor use because of worsening heart failure. The increased event numbers allowed the researchers to perform 30 additional analyses included in this report, according to the count kept by Dr. Packer who was the lead author.

He highlighted several of the additional results in this paper that documented benefits from empagliflozin treatment, compared with placebo:

• A significant 29% reduction in the need for admission to a cardiac care unit or intensive care unit during an HHF.
• A nonsignificant 33% reduction in the need for intravenous vasopressors or positive inotropic drugs during HHF.
• A significantly increased rate of patients achieving a higher New York Heart Association functional class. For example, after the first year of treatment patients who received empagliflozin had a 37% higher rate of functional class improvement, compared with patients who received placebo.

Dr. McMurray had his own list of key takeaways from this paper, including:

• Among patients who needed hospitalization, “those treated with empagliflozin were less sick than those in the placebo group.”
• In addition to reducing HHF empagliflozin treatment also reduced episodes of outpatient worsening as reflected by their receipt of intensified diuretic treatment, which occurred a significant 27% less often, compared with patients on placebo.
• Treatment with empagliflozin also linked with a significant 39% relative reduction in emergency or urgent-care visits that required intravenous therapy.

Empagliflozin’s performance relative to sacubitril/valsartan

The fourth additional report focused on a post hoc, cross-trial comparison of the results from EMPEROR-Preserved and from another recent trial that, like EMPEROR-Preserved, assessed in patients with HFpEF a drug previously proven to work quite well in patients with HFrEF. The comparator drug was sacubitril/valsartan (Entresto), which underwent testing in patients with HFpEF in the PARAGON-HF trial.

The primary outcome of PARAGON-HF, which randomized 4,822 patients, was reduction in cardiovascular death and in total HHF. This dropped by a relative 13%, compared with placebo, during a median of 35 months, a between-group difference that came close to but did not achieve significance (P = .06). Despite this limitation, the Food and Drug Administration in February 2021 loosened the indication for using sacubitril/valsartan in patients with heart failure and a “below normal” ejection fraction, a category that can include many patients considered to have HFpEF.

Although the researchers who ran this analysis, including Dr. Packer, who was the first author, admitted that “comparison of effect sizes across trials is fraught with difficulties,” they nonetheless concluded from their analysis that “for all outcomes that included HHF the effect size was larger for empagliflozin than for sacubitril/valsartan.”

Dr. McMurray, a lead instigator for PARAGON-HF, said there was little to take away from this analysis.

“The patient populations were different, and sacubitril/valsartan was compared against an active therapy, valsartan,” while in EMPEROR-Preserved empagliflozin compared against placebo. “Most of us believe that sacubitril/valsartan and SGLT2 inhibitors work in different but complementary ways, and their benefits are additive. You would want patients with HFpEF or HFrEF to take both,” he said in an interview.

Dr. Packer agreed with that approach and added that he would probably also prescribe a third agent, spironolactone, to many patients with HFpEF.

EMPEROR-Preserved was sponsored by Boehringer Ingelheim and Eli Lilly, which jointly market empagliflozin (Jardiance). PARAGON-HF was sponsored by Novartis, which markets sacubitril/valsartan (Entresto). Dr. Packer has received consulting fees from Boehringer Ingelheim and from numerous other companies. Dr. de Boer has research contracts with Boehringer Ingelheim as well as from Abbott, AstraZeneca, Cardior, Ionis, Novo Nordisk, and Roche, and he has been a consultant to Novartis as well as to Abbott, AstraZeneca, Gayer, and Roche. Dr. McMurray led trials of sacubitril/valsartan sponsored by Novartis, and his institution has received compensation for his participation in studies sponsored by Abbvie, AstraZeneca, Cardurion, DalCor, GlaxoSmithKline, Pfizer, and Theracos.

[email protected]

The featured report from the 6,000-patient EMPEROR-Preserved trial at the virtual annual congress of the European Society of Cardiology drew lots of attention for its headline finding: the first unequivocal demonstration that a medication, empagliflozin, can significantly reduce the rate of cardiovascular death and hospitalization for heart failure in patients with heart failure with preserved ejection fraction (HFpEF, a left ventricular ejection fraction of more than 40%), with the details simultaneously published online.

But at the same time, the EMPEROR-Preserved investigators released four additional reports with a lot more outcome analyses that also deserve some attention.
 

The puzzling neutral effect on renal events

Perhaps the most surprising and complicated set of findings among the main EMPEROR-Preserved outcomes involved renal outcomes.

The trial’s primary outcome was the combined rate of cardiovascular death or hospitalization for heart failure (HHF), and the results showed that treatment with empagliflozin (Jardiance) for a median of 26 months on top of standard treatment for patients with HFpEF led to a significant 21% relative risk reduction, compared with placebo-treated patients.

The trial had two prespecified secondary outcomes. One was the total number of HHF, which dropped by a significant 27%, compared with placebo. The second was the mean change in slope of estimated glomerular filtration rate (eGFR) on an annualized basis, and the empagliflozin regimen reduced the cumulative annual deficit, compared with placebo by an average of 1.36 mL/min per 1.73 m^2, a significant difference.

This preservation of renal function was consistent with results from many prior studies of empagliflozin and all of the other U.S.-approved agents from the sodium-glucose cotransporter 2 inhibitor class. Preservation of renal function and a reduction in renal events has become a hallmark property of all agents in the SGLT2 inhibitor class both in patients with type 2 diabetes, as well as in those without diabetes but with heart failure with reduced ejection fraction (HFrEF) or with chronic kidney disease.

EMPEROR-Preserved threw a wrench into what had been an unbroken history of renal protection by SGLT2 inhibitors. That happened when a prespecified endpoint of the study – a composite renal outcome defined as time to first occurrence of chronic dialysis, renal transplantation, a sustained reduction of at least 40% in eGFR, or a sustained drop in eGFR of more than 10 or 15 mL/min per 1.73 m2 from baseline – yielded an unexpected neutral finding.

For this composite renal outcome, EMPEROR-Preserved showed a nonsignificant 5% reduction, compared with placebo, a result that both differed from what had been seen in essentially all the other SGLT2 inhibitor trials that had looked at this, but which also seemed at odds with the observed significant preservation of renal function that seemed substantial enough to produce a clinically meaningful benefit.
 

Renal effects blunted in HFpEF

The immediate upshot was a letter published by several EMPEROR-Preserved investigators that spelled out this discrepancy and came to the jolting conclusion that “eGFR slope analysis has limitations as a surrogate for predicting the effect of drugs on renal outcomes in patients with heart failure.”

The same authors, along with some additional associates, also published a second letter that noted a further unexpected twist with the renal outcome: “In prior large-scale clinical trials, the effect of SGLT2 inhibitors on heart failure and renal outcomes had consistently tracked together,” they noted, but in this case it didn’t, a discordance they said was “extraordinarily puzzling”.

MDedge News

This led the study’s leaders to reanalyze the renal outcomes using a different definition, one that Milton Packer, MD, who helped design the trial and oversaw several of its analyses, called “a more conventional definition of renal events,” during his presentation of these findings at the congress. The researchers swapped out a 40% drop from baseline eGFR as an event and replaced it with a 50% decline, a change designed to screen out less severe, and often transient, reductions in kidney function that have less lasting impact on health. They also added an additional component to the composite endpoint, renal death. A revised analysis using this new renal composite outcome appeared in the European Journal of Heart Failure letter.

This change cut the total number of renal events tallied in the trial nearly in half, down to 112, and showed a more robust decline in renal events with empagliflozin treatment compared with the initial analysis, although the drop remained nonsignificant. The revised analysis also showed that the overall, nonsignificant 22% relative reduction in renal events in patients on empagliflozin, compared with placebo, dwindled down to completely nonexistent in the tertile of patients with a left ventricular ejection fraction of 60% or greater. In this tertile the hazard ratio actually showed a nonsignificant point estimate of a 24% increased rate of renal events on empagliflozin, with the caveat that this subgroup now included a total of just 40 total events between the two treatment arms. (Each of the two other tertiles also had roughly the same number of total events.)

The biggest effect on renal-event reduction was in the tertile of patients with an ejection fraction of 41%-49%, in which empagliflozin treatment was linked with a significant 59% cut in renal events, compared with placebo. The analysis also showed significant heterogeneity in thus outcome between this subgroup and the other two tertiles that had higher ejection fractions and showed reduced rates of protection by empagliflozin against renal events.

This apparent blunting of a renal effect despite preservation of renal function seemed to mimic the blunting of the primary cardiovascular outcome effect that also appeared in patients with ejection fractions in the 60%-65% range or above.

“If we knew what blunted the effect of empagliflozin on heart failure outcomes at higher ejection fraction levels, we think the same explanation may also apply to the blunting of effect on renal outcomes, but right now we do not know the answer to either question,” Dr. Packer said in an interview. He’s suggested that one possibility is that many of the enrolled patients identified as having HFpEF, but with these high ejection fractions may have not actually had HFpEF, and their signs and symptoms may have instead resulted from atrial fibrillation.

“Many patients with an ejection fraction of 60%-65% and above had atrial fibrillation,” he noted, with a prevalence at enrollment in this subgroup of about 50%. Atrial fibrillation can cause dyspnea, a hallmark symptom leading to diagnosis of heart failure, and it also increases levels of N-terminal of the prohormone brain natriuretic peptide, a metric that served as a gatekeeper for entry into the trial. “Essentially, we are saying that many of the criteria that we specified to ensure that patients had heart failure probably did not work very well in patients with an ejection fraction of 65% or greater,” said Dr. Packer, a cardiologist at Baylor University Medical Center in Dallas. “We need to figure out who these patients are.”

Some experts not involved with the study voiced skepticism that the renal findings reflected a real issue.

“I’m quite optimistic that in the long-term the effect on eGFR will translate into renal protection,” said Rudolf A. de Boer, MD, PhD, a professor of translational cardiology at University Medical Center Groningen (the Netherlands), and designated discussant at the congress for the presentation by Dr. Packer.

Catherine Hackett/MDedge News

John J.V. McMurray, MD, a professor of cardiology and a heart failure specialist at Glasgow University, speculated that the unexpected renal outcomes data may relate to the initial decline in renal function produced by treatment with SGLT2 inhibitors despite their longer-term enhancement of renal protection.

“If you use a treatment that protects the kidneys in the long-term but causes an initial dip in eGFR, more patients receiving that treatment will have an early ‘event,’ ” he noted in an interview. He also cautioned about the dangers of subgroup analyses that dice the study population into small cohorts.

“Trials are powered to look at the effect of treatment in the overall population. Everything else is exploratory, underpowered, and subject to the play of chance,” Dr. McMurray stressed.
 

Counting additional cardiovascular disease events allows more analyses

A third auxiliary report from the EMPEROR-Preserved investigators performed several prespecified analyses that depended on adding additional cardiovascular disease endpoints to the core tallies of cardiovascular death or HHF – such as emergent, urgent, and outpatient events that reflected worsening heart failure – and also included information on diuretic and vasopressor use because of worsening heart failure. The increased event numbers allowed the researchers to perform 30 additional analyses included in this report, according to the count kept by Dr. Packer who was the lead author.

He highlighted several of the additional results in this paper that documented benefits from empagliflozin treatment, compared with placebo:

• A significant 29% reduction in the need for admission to a cardiac care unit or intensive care unit during an HHF.
• A nonsignificant 33% reduction in the need for intravenous vasopressors or positive inotropic drugs during HHF.
• A significantly increased rate of patients achieving a higher New York Heart Association functional class. For example, after the first year of treatment patients who received empagliflozin had a 37% higher rate of functional class improvement, compared with patients who received placebo.

Dr. McMurray had his own list of key takeaways from this paper, including:

• Among patients who needed hospitalization, “those treated with empagliflozin were less sick than those in the placebo group.”
• In addition to reducing HHF empagliflozin treatment also reduced episodes of outpatient worsening as reflected by their receipt of intensified diuretic treatment, which occurred a significant 27% less often, compared with patients on placebo.
• Treatment with empagliflozin also linked with a significant 39% relative reduction in emergency or urgent-care visits that required intravenous therapy.

Empagliflozin’s performance relative to sacubitril/valsartan

The fourth additional report focused on a post hoc, cross-trial comparison of the results from EMPEROR-Preserved and from another recent trial that, like EMPEROR-Preserved, assessed in patients with HFpEF a drug previously proven to work quite well in patients with HFrEF. The comparator drug was sacubitril/valsartan (Entresto), which underwent testing in patients with HFpEF in the PARAGON-HF trial.

The primary outcome of PARAGON-HF, which randomized 4,822 patients, was reduction in cardiovascular death and in total HHF. This dropped by a relative 13%, compared with placebo, during a median of 35 months, a between-group difference that came close to but did not achieve significance (P = .06). Despite this limitation, the Food and Drug Administration in February 2021 loosened the indication for using sacubitril/valsartan in patients with heart failure and a “below normal” ejection fraction, a category that can include many patients considered to have HFpEF.

Although the researchers who ran this analysis, including Dr. Packer, who was the first author, admitted that “comparison of effect sizes across trials is fraught with difficulties,” they nonetheless concluded from their analysis that “for all outcomes that included HHF the effect size was larger for empagliflozin than for sacubitril/valsartan.”

Dr. McMurray, a lead instigator for PARAGON-HF, said there was little to take away from this analysis.

“The patient populations were different, and sacubitril/valsartan was compared against an active therapy, valsartan,” while in EMPEROR-Preserved empagliflozin compared against placebo. “Most of us believe that sacubitril/valsartan and SGLT2 inhibitors work in different but complementary ways, and their benefits are additive. You would want patients with HFpEF or HFrEF to take both,” he said in an interview.

Dr. Packer agreed with that approach and added that he would probably also prescribe a third agent, spironolactone, to many patients with HFpEF.

EMPEROR-Preserved was sponsored by Boehringer Ingelheim and Eli Lilly, which jointly market empagliflozin (Jardiance). PARAGON-HF was sponsored by Novartis, which markets sacubitril/valsartan (Entresto). Dr. Packer has received consulting fees from Boehringer Ingelheim and from numerous other companies. Dr. de Boer has research contracts with Boehringer Ingelheim as well as from Abbott, AstraZeneca, Cardior, Ionis, Novo Nordisk, and Roche, and he has been a consultant to Novartis as well as to Abbott, AstraZeneca, Gayer, and Roche. Dr. McMurray led trials of sacubitril/valsartan sponsored by Novartis, and his institution has received compensation for his participation in studies sponsored by Abbvie, AstraZeneca, Cardurion, DalCor, GlaxoSmithKline, Pfizer, and Theracos.

[email protected]

The featured report from the 6,000-patient EMPEROR-Preserved trial at the virtual annual congress of the European Society of Cardiology drew lots of attention for its headline finding: the first unequivocal demonstration that a medication, empagliflozin, can significantly reduce the rate of cardiovascular death and hospitalization for heart failure in patients with heart failure with preserved ejection fraction (HFpEF, a left ventricular ejection fraction of more than 40%), with the details simultaneously published online.

But at the same time, the EMPEROR-Preserved investigators released four additional reports with a lot more outcome analyses that also deserve some attention.
 

The puzzling neutral effect on renal events

Perhaps the most surprising and complicated set of findings among the main EMPEROR-Preserved outcomes involved renal outcomes.

The trial’s primary outcome was the combined rate of cardiovascular death or hospitalization for heart failure (HHF), and the results showed that treatment with empagliflozin (Jardiance) for a median of 26 months on top of standard treatment for patients with HFpEF led to a significant 21% relative risk reduction, compared with placebo-treated patients.

The trial had two prespecified secondary outcomes. One was the total number of HHF, which dropped by a significant 27%, compared with placebo. The second was the mean change in slope of estimated glomerular filtration rate (eGFR) on an annualized basis, and the empagliflozin regimen reduced the cumulative annual deficit, compared with placebo by an average of 1.36 mL/min per 1.73 m^2, a significant difference.

This preservation of renal function was consistent with results from many prior studies of empagliflozin and all of the other U.S.-approved agents from the sodium-glucose cotransporter 2 inhibitor class. Preservation of renal function and a reduction in renal events has become a hallmark property of all agents in the SGLT2 inhibitor class both in patients with type 2 diabetes, as well as in those without diabetes but with heart failure with reduced ejection fraction (HFrEF) or with chronic kidney disease.

EMPEROR-Preserved threw a wrench into what had been an unbroken history of renal protection by SGLT2 inhibitors. That happened when a prespecified endpoint of the study – a composite renal outcome defined as time to first occurrence of chronic dialysis, renal transplantation, a sustained reduction of at least 40% in eGFR, or a sustained drop in eGFR of more than 10 or 15 mL/min per 1.73 m2 from baseline – yielded an unexpected neutral finding.

For this composite renal outcome, EMPEROR-Preserved showed a nonsignificant 5% reduction, compared with placebo, a result that both differed from what had been seen in essentially all the other SGLT2 inhibitor trials that had looked at this, but which also seemed at odds with the observed significant preservation of renal function that seemed substantial enough to produce a clinically meaningful benefit.
 

Renal effects blunted in HFpEF

The immediate upshot was a letter published by several EMPEROR-Preserved investigators that spelled out this discrepancy and came to the jolting conclusion that “eGFR slope analysis has limitations as a surrogate for predicting the effect of drugs on renal outcomes in patients with heart failure.”

The same authors, along with some additional associates, also published a second letter that noted a further unexpected twist with the renal outcome: “In prior large-scale clinical trials, the effect of SGLT2 inhibitors on heart failure and renal outcomes had consistently tracked together,” they noted, but in this case it didn’t, a discordance they said was “extraordinarily puzzling”.

MDedge News

This led the study’s leaders to reanalyze the renal outcomes using a different definition, one that Milton Packer, MD, who helped design the trial and oversaw several of its analyses, called “a more conventional definition of renal events,” during his presentation of these findings at the congress. The researchers swapped out a 40% drop from baseline eGFR as an event and replaced it with a 50% decline, a change designed to screen out less severe, and often transient, reductions in kidney function that have less lasting impact on health. They also added an additional component to the composite endpoint, renal death. A revised analysis using this new renal composite outcome appeared in the European Journal of Heart Failure letter.

This change cut the total number of renal events tallied in the trial nearly in half, down to 112, and showed a more robust decline in renal events with empagliflozin treatment compared with the initial analysis, although the drop remained nonsignificant. The revised analysis also showed that the overall, nonsignificant 22% relative reduction in renal events in patients on empagliflozin, compared with placebo, dwindled down to completely nonexistent in the tertile of patients with a left ventricular ejection fraction of 60% or greater. In this tertile the hazard ratio actually showed a nonsignificant point estimate of a 24% increased rate of renal events on empagliflozin, with the caveat that this subgroup now included a total of just 40 total events between the two treatment arms. (Each of the two other tertiles also had roughly the same number of total events.)

The biggest effect on renal-event reduction was in the tertile of patients with an ejection fraction of 41%-49%, in which empagliflozin treatment was linked with a significant 59% cut in renal events, compared with placebo. The analysis also showed significant heterogeneity in thus outcome between this subgroup and the other two tertiles that had higher ejection fractions and showed reduced rates of protection by empagliflozin against renal events.

This apparent blunting of a renal effect despite preservation of renal function seemed to mimic the blunting of the primary cardiovascular outcome effect that also appeared in patients with ejection fractions in the 60%-65% range or above.

“If we knew what blunted the effect of empagliflozin on heart failure outcomes at higher ejection fraction levels, we think the same explanation may also apply to the blunting of effect on renal outcomes, but right now we do not know the answer to either question,” Dr. Packer said in an interview. He’s suggested that one possibility is that many of the enrolled patients identified as having HFpEF, but with these high ejection fractions may have not actually had HFpEF, and their signs and symptoms may have instead resulted from atrial fibrillation.

“Many patients with an ejection fraction of 60%-65% and above had atrial fibrillation,” he noted, with a prevalence at enrollment in this subgroup of about 50%. Atrial fibrillation can cause dyspnea, a hallmark symptom leading to diagnosis of heart failure, and it also increases levels of N-terminal of the prohormone brain natriuretic peptide, a metric that served as a gatekeeper for entry into the trial. “Essentially, we are saying that many of the criteria that we specified to ensure that patients had heart failure probably did not work very well in patients with an ejection fraction of 65% or greater,” said Dr. Packer, a cardiologist at Baylor University Medical Center in Dallas. “We need to figure out who these patients are.”

Some experts not involved with the study voiced skepticism that the renal findings reflected a real issue.

“I’m quite optimistic that in the long-term the effect on eGFR will translate into renal protection,” said Rudolf A. de Boer, MD, PhD, a professor of translational cardiology at University Medical Center Groningen (the Netherlands), and designated discussant at the congress for the presentation by Dr. Packer.

Catherine Hackett/MDedge News

John J.V. McMurray, MD, a professor of cardiology and a heart failure specialist at Glasgow University, speculated that the unexpected renal outcomes data may relate to the initial decline in renal function produced by treatment with SGLT2 inhibitors despite their longer-term enhancement of renal protection.

“If you use a treatment that protects the kidneys in the long-term but causes an initial dip in eGFR, more patients receiving that treatment will have an early ‘event,’ ” he noted in an interview. He also cautioned about the dangers of subgroup analyses that dice the study population into small cohorts.

“Trials are powered to look at the effect of treatment in the overall population. Everything else is exploratory, underpowered, and subject to the play of chance,” Dr. McMurray stressed.
 

Counting additional cardiovascular disease events allows more analyses

A third auxiliary report from the EMPEROR-Preserved investigators performed several prespecified analyses that depended on adding additional cardiovascular disease endpoints to the core tallies of cardiovascular death or HHF – such as emergent, urgent, and outpatient events that reflected worsening heart failure – and also included information on diuretic and vasopressor use because of worsening heart failure. The increased event numbers allowed the researchers to perform 30 additional analyses included in this report, according to the count kept by Dr. Packer who was the lead author.

He highlighted several of the additional results in this paper that documented benefits from empagliflozin treatment, compared with placebo:

• A significant 29% reduction in the need for admission to a cardiac care unit or intensive care unit during an HHF.
• A nonsignificant 33% reduction in the need for intravenous vasopressors or positive inotropic drugs during HHF.
• A significantly increased rate of patients achieving a higher New York Heart Association functional class. For example, after the first year of treatment patients who received empagliflozin had a 37% higher rate of functional class improvement, compared with patients who received placebo.

Dr. McMurray had his own list of key takeaways from this paper, including:

• Among patients who needed hospitalization, “those treated with empagliflozin were less sick than those in the placebo group.”
• In addition to reducing HHF empagliflozin treatment also reduced episodes of outpatient worsening as reflected by their receipt of intensified diuretic treatment, which occurred a significant 27% less often, compared with patients on placebo.
• Treatment with empagliflozin also linked with a significant 39% relative reduction in emergency or urgent-care visits that required intravenous therapy.

Empagliflozin’s performance relative to sacubitril/valsartan

The fourth additional report focused on a post hoc, cross-trial comparison of the results from EMPEROR-Preserved and from another recent trial that, like EMPEROR-Preserved, assessed in patients with HFpEF a drug previously proven to work quite well in patients with HFrEF. The comparator drug was sacubitril/valsartan (Entresto), which underwent testing in patients with HFpEF in the PARAGON-HF trial.

The primary outcome of PARAGON-HF, which randomized 4,822 patients, was reduction in cardiovascular death and in total HHF. This dropped by a relative 13%, compared with placebo, during a median of 35 months, a between-group difference that came close to but did not achieve significance (P = .06). Despite this limitation, the Food and Drug Administration in February 2021 loosened the indication for using sacubitril/valsartan in patients with heart failure and a “below normal” ejection fraction, a category that can include many patients considered to have HFpEF.

Although the researchers who ran this analysis, including Dr. Packer, who was the first author, admitted that “comparison of effect sizes across trials is fraught with difficulties,” they nonetheless concluded from their analysis that “for all outcomes that included HHF the effect size was larger for empagliflozin than for sacubitril/valsartan.”

Dr. McMurray, a lead instigator for PARAGON-HF, said there was little to take away from this analysis.

“The patient populations were different, and sacubitril/valsartan was compared against an active therapy, valsartan,” while in EMPEROR-Preserved empagliflozin compared against placebo. “Most of us believe that sacubitril/valsartan and SGLT2 inhibitors work in different but complementary ways, and their benefits are additive. You would want patients with HFpEF or HFrEF to take both,” he said in an interview.

Dr. Packer agreed with that approach and added that he would probably also prescribe a third agent, spironolactone, to many patients with HFpEF.

EMPEROR-Preserved was sponsored by Boehringer Ingelheim and Eli Lilly, which jointly market empagliflozin (Jardiance). PARAGON-HF was sponsored by Novartis, which markets sacubitril/valsartan (Entresto). Dr. Packer has received consulting fees from Boehringer Ingelheim and from numerous other companies. Dr. de Boer has research contracts with Boehringer Ingelheim as well as from Abbott, AstraZeneca, Cardior, Ionis, Novo Nordisk, and Roche, and he has been a consultant to Novartis as well as to Abbott, AstraZeneca, Gayer, and Roche. Dr. McMurray led trials of sacubitril/valsartan sponsored by Novartis, and his institution has received compensation for his participation in studies sponsored by Abbvie, AstraZeneca, Cardurion, DalCor, GlaxoSmithKline, Pfizer, and Theracos.

[email protected]

Healthy elderly people who ate a walnut-supplemented diet for 2 years showed significant reductions in LDL cholesterol, according to a randomized study that used imaging to evaluate lipid changes.

©rootstocks/Thinkstock

“Regularly eating walnuts will lower your LDL cholesterol and improve the quality of LDL particles, rendering them less prone to enter the arterial wall and build up atherosclerosis, and this will occur without unwanted weight gain in spite of the high-fat – healthy vegetable fat, though – content of walnuts,” Emilio Ros, MD, PhD, senior author of the Walnuts and Healthy Aging (WAHA) study, said in an interview.

WAHA is a parallel-group, randomized, controlled trial that followed 636 patients over 2 years at centers in Loma Linda, Calif., and Barcelona. They were randomly assigned to either a walnut-free or walnut-supplemented diet, and every 2 months they were underwent nuclear magnetic resonance spectroscopy and recorded their compliance, toleration, medication changes, and body weight.

The researchers reported “significantly decreased” total cholesterol, LDL cholesterol and intermediate-density lipoprotein cholesterol, along with reductions in total LDL cholesterol particles and small LDL cholesterol particle number in patients on a walnut-supplemented diet, compared with controls. However, triglycerides and HDL cholesterol were unaffected.

Study results

The study reported mean reductions in the following lipid categories among what the researchers called the “walnut group”:

• Total cholesterol, –8.5 mg/dL (95% confidence interval, –11.2 to –5.4), a 4.4% mean reduction.
• LDL-C, –4.3 mg/dL (95% CI, –6.6 to –1.6), a 3.6% reduction.
• Intermediate-density lipoprotein cholesterol, –1.3 mg/dL (95% CI, –1.5 to –1.0] for a 16.8% reduction.
• Total LDL cholesterol particles, a reduction of 4.3%.
• Small LDL cholesterol particle number, a 6.1% decrease.

“WAHA is the largest and longest randomized nut trial to date, which overcomes power limitations of former trials, smaller and of shorter duration,” said Dr. Ros, of the lipid clinic, endocrinology, nutrition service at the Hospital Clinic Villarroel at the University of Barcelona. He noted that studies he has participated in have already shown that the walnut-supplemented diet had beneficial effects on blood pressure, systemic inflammation and endothelial function.

Other strengths of the study, he said, were that it recruited patients from two distinct locations and that it retained 90% of participants over 2 years (the study started out with 708 participants).

Christie Ballantyne, MD, concurred that the size and duration of the study are worth noting. “People always have questions about what they should eat,” said Dr. Ballantyne, chief of cardiology at Baylor College of Medicine and director of cardiovascular disease prevention at Methodist DeBakey Heart Center, both in Houston, said in an interview. “It’s very difficult to do nutritional studies. Most studies are small and short term, so it’s unusual to have study that’s large with 2 years of follow-up. This is a larger-than-usual study.”

Potential study limitations

Dr. Ros did acknowledge some limitations of the study. Participants weren’t blinded, the feeding setting wasn’t controlled, and participants were generally healthy and had average normal lipid profiles because they were taking statins, which may explain the modest lipid improvements in the study. “LDL cholesterol lowering by nuts is related to baseline levels, hence the reduction observed in our study was modest,” he said.

Additionally, because the study group was elderly, the results don’t apply to younger people. “Yet,” Dr. Ros added, “we know from many prior studies that nuts in general and walnuts in particular will lower blood cholesterol regardless of age.”

Dr. Ballantyne noted that the use of nuclear magnetic resonance spectroscopy to evaluate lipid levels involves a methodology that isn’t as systematic or as standardized as the typical lipid profile, and that different systems use proprietary software to interpret results. “That’s a little bit of an issue,” he said. “What exactly do the numbers mean?”

Overall, though, Dr. Ballantyne said the study is a significant addition to the literature. “The study is large, well done, and it confirms the benefits of something we’ve been telling patients is a good choice. It’s useful because there’s so much noise. It is important because there’s tremendous confusion and misinformation about what’s really healthy to eat.”

The study was supported by a grant from the California Walnut Commission (CWC), from which Dr. Ros and two coauthors received research funding through their institutions. Dr. Ros also reported receiving compensation from CWC and serves on a CWC advisory council. The other authors have no relationships to disclose. The WAHA study was supported by a grant from the CWC, from which Dr. Ros and some coinvestigators have received research funding through their institutions. Dr. Ballantyne has no relevant relationships to disclose.

Healthy elderly people who ate a walnut-supplemented diet for 2 years showed significant reductions in LDL cholesterol, according to a randomized study that used imaging to evaluate lipid changes.

©rootstocks/Thinkstock

“Regularly eating walnuts will lower your LDL cholesterol and improve the quality of LDL particles, rendering them less prone to enter the arterial wall and build up atherosclerosis, and this will occur without unwanted weight gain in spite of the high-fat – healthy vegetable fat, though – content of walnuts,” Emilio Ros, MD, PhD, senior author of the Walnuts and Healthy Aging (WAHA) study, said in an interview.

WAHA is a parallel-group, randomized, controlled trial that followed 636 patients over 2 years at centers in Loma Linda, Calif., and Barcelona. They were randomly assigned to either a walnut-free or walnut-supplemented diet, and every 2 months they were underwent nuclear magnetic resonance spectroscopy and recorded their compliance, toleration, medication changes, and body weight.

The researchers reported “significantly decreased” total cholesterol, LDL cholesterol and intermediate-density lipoprotein cholesterol, along with reductions in total LDL cholesterol particles and small LDL cholesterol particle number in patients on a walnut-supplemented diet, compared with controls. However, triglycerides and HDL cholesterol were unaffected.

Study results

The study reported mean reductions in the following lipid categories among what the researchers called the “walnut group”:

• Total cholesterol, –8.5 mg/dL (95% confidence interval, –11.2 to –5.4), a 4.4% mean reduction.
• LDL-C, –4.3 mg/dL (95% CI, –6.6 to –1.6), a 3.6% reduction.
• Intermediate-density lipoprotein cholesterol, –1.3 mg/dL (95% CI, –1.5 to –1.0] for a 16.8% reduction.
• Total LDL cholesterol particles, a reduction of 4.3%.
• Small LDL cholesterol particle number, a 6.1% decrease.

“WAHA is the largest and longest randomized nut trial to date, which overcomes power limitations of former trials, smaller and of shorter duration,” said Dr. Ros, of the lipid clinic, endocrinology, nutrition service at the Hospital Clinic Villarroel at the University of Barcelona. He noted that studies he has participated in have already shown that the walnut-supplemented diet had beneficial effects on blood pressure, systemic inflammation and endothelial function.

Other strengths of the study, he said, were that it recruited patients from two distinct locations and that it retained 90% of participants over 2 years (the study started out with 708 participants).

Christie Ballantyne, MD, concurred that the size and duration of the study are worth noting. “People always have questions about what they should eat,” said Dr. Ballantyne, chief of cardiology at Baylor College of Medicine and director of cardiovascular disease prevention at Methodist DeBakey Heart Center, both in Houston, said in an interview. “It’s very difficult to do nutritional studies. Most studies are small and short term, so it’s unusual to have study that’s large with 2 years of follow-up. This is a larger-than-usual study.”

Potential study limitations

Dr. Ros did acknowledge some limitations of the study. Participants weren’t blinded, the feeding setting wasn’t controlled, and participants were generally healthy and had average normal lipid profiles because they were taking statins, which may explain the modest lipid improvements in the study. “LDL cholesterol lowering by nuts is related to baseline levels, hence the reduction observed in our study was modest,” he said.

Additionally, because the study group was elderly, the results don’t apply to younger people. “Yet,” Dr. Ros added, “we know from many prior studies that nuts in general and walnuts in particular will lower blood cholesterol regardless of age.”

Dr. Ballantyne noted that the use of nuclear magnetic resonance spectroscopy to evaluate lipid levels involves a methodology that isn’t as systematic or as standardized as the typical lipid profile, and that different systems use proprietary software to interpret results. “That’s a little bit of an issue,” he said. “What exactly do the numbers mean?”

Overall, though, Dr. Ballantyne said the study is a significant addition to the literature. “The study is large, well done, and it confirms the benefits of something we’ve been telling patients is a good choice. It’s useful because there’s so much noise. It is important because there’s tremendous confusion and misinformation about what’s really healthy to eat.”

The study was supported by a grant from the California Walnut Commission (CWC), from which Dr. Ros and two coauthors received research funding through their institutions. Dr. Ros also reported receiving compensation from CWC and serves on a CWC advisory council. The other authors have no relationships to disclose. The WAHA study was supported by a grant from the CWC, from which Dr. Ros and some coinvestigators have received research funding through their institutions. Dr. Ballantyne has no relevant relationships to disclose.

Healthy elderly people who ate a walnut-supplemented diet for 2 years showed significant reductions in LDL cholesterol, according to a randomized study that used imaging to evaluate lipid changes.

©rootstocks/Thinkstock

“Regularly eating walnuts will lower your LDL cholesterol and improve the quality of LDL particles, rendering them less prone to enter the arterial wall and build up atherosclerosis, and this will occur without unwanted weight gain in spite of the high-fat – healthy vegetable fat, though – content of walnuts,” Emilio Ros, MD, PhD, senior author of the Walnuts and Healthy Aging (WAHA) study, said in an interview.

WAHA is a parallel-group, randomized, controlled trial that followed 636 patients over 2 years at centers in Loma Linda, Calif., and Barcelona. They were randomly assigned to either a walnut-free or walnut-supplemented diet, and every 2 months they were underwent nuclear magnetic resonance spectroscopy and recorded their compliance, toleration, medication changes, and body weight.

The researchers reported “significantly decreased” total cholesterol, LDL cholesterol and intermediate-density lipoprotein cholesterol, along with reductions in total LDL cholesterol particles and small LDL cholesterol particle number in patients on a walnut-supplemented diet, compared with controls. However, triglycerides and HDL cholesterol were unaffected.

Study results

The study reported mean reductions in the following lipid categories among what the researchers called the “walnut group”:

• Total cholesterol, –8.5 mg/dL (95% confidence interval, –11.2 to –5.4), a 4.4% mean reduction.
• LDL-C, –4.3 mg/dL (95% CI, –6.6 to –1.6), a 3.6% reduction.
• Intermediate-density lipoprotein cholesterol, –1.3 mg/dL (95% CI, –1.5 to –1.0] for a 16.8% reduction.
• Total LDL cholesterol particles, a reduction of 4.3%.
• Small LDL cholesterol particle number, a 6.1% decrease.

“WAHA is the largest and longest randomized nut trial to date, which overcomes power limitations of former trials, smaller and of shorter duration,” said Dr. Ros, of the lipid clinic, endocrinology, nutrition service at the Hospital Clinic Villarroel at the University of Barcelona. He noted that studies he has participated in have already shown that the walnut-supplemented diet had beneficial effects on blood pressure, systemic inflammation and endothelial function.

Other strengths of the study, he said, were that it recruited patients from two distinct locations and that it retained 90% of participants over 2 years (the study started out with 708 participants).

Christie Ballantyne, MD, concurred that the size and duration of the study are worth noting. “People always have questions about what they should eat,” said Dr. Ballantyne, chief of cardiology at Baylor College of Medicine and director of cardiovascular disease prevention at Methodist DeBakey Heart Center, both in Houston, said in an interview. “It’s very difficult to do nutritional studies. Most studies are small and short term, so it’s unusual to have study that’s large with 2 years of follow-up. This is a larger-than-usual study.”

Potential study limitations

Dr. Ros did acknowledge some limitations of the study. Participants weren’t blinded, the feeding setting wasn’t controlled, and participants were generally healthy and had average normal lipid profiles because they were taking statins, which may explain the modest lipid improvements in the study. “LDL cholesterol lowering by nuts is related to baseline levels, hence the reduction observed in our study was modest,” he said.

Additionally, because the study group was elderly, the results don’t apply to younger people. “Yet,” Dr. Ros added, “we know from many prior studies that nuts in general and walnuts in particular will lower blood cholesterol regardless of age.”

Dr. Ballantyne noted that the use of nuclear magnetic resonance spectroscopy to evaluate lipid levels involves a methodology that isn’t as systematic or as standardized as the typical lipid profile, and that different systems use proprietary software to interpret results. “That’s a little bit of an issue,” he said. “What exactly do the numbers mean?”

Overall, though, Dr. Ballantyne said the study is a significant addition to the literature. “The study is large, well done, and it confirms the benefits of something we’ve been telling patients is a good choice. It’s useful because there’s so much noise. It is important because there’s tremendous confusion and misinformation about what’s really healthy to eat.”

The study was supported by a grant from the California Walnut Commission (CWC), from which Dr. Ros and two coauthors received research funding through their institutions. Dr. Ros also reported receiving compensation from CWC and serves on a CWC advisory council. The other authors have no relationships to disclose. The WAHA study was supported by a grant from the CWC, from which Dr. Ros and some coinvestigators have received research funding through their institutions. Dr. Ballantyne has no relevant relationships to disclose.

There will be so much more to the annual congress of the European Society of Cardiology, which begins Aug. 27 with an all-virtual format, than detailed primary results of EMPEROR-Preserved, a trial that could mark a turning point for heart failure (HF) medical therapy.

Also among the featured Hot Line and Late-Breaking Science sessions are – along with many other studies – explorations of arrhythmia management (ablation or guided by loop recorder); secondary prevention, including by vaccination; oral anticoagulation, notably after transcatheter valve procedures; and colchicine or thrombosis prophylaxis in hospitalized patients with COVID-19.

There will even be a head-to-head comparison of two long-familiar left atrial appendage (LAA) occluders, and a population-based, randomized trial of sodium restriction through wide-scale use of a potassium-based salt substitute.

The congress will also introduce four guideline documents at sessions throughout the Congress, one on each day. They cover new and modified recommendations for heart failure; pacing, including cardiac resynchronization therapy (CRT); cardiovascular (CV) disease prevention; and, with cosponsorship from the European Association for Cardio-Thoracic Surgery, valvular heart disease.
 

The virtues of virtual

That next year’s Congress is slated for Aug. 27-30 in Barcelona should be welcome news for anyone whose “what if” curiosity about all-virtual conferences has already been satisfied. But with experience comes wisdom, as the medical societies have learned that online scientific meetings have some winning qualities that may be worth keeping, as least for a while.

“I think there is no doubt that the digital format will continue, for several reasons. One is that this pandemic is not over,” ESC Congress program committee chair Stephan Windecker, MD, Bern (Switzerland) University Hospital, , told this news organization. “As long as it is not over, the digital format is here to stay.”

But it also appears that people who haven’t been able to attend the congress in person are keen to log in and engage online, Dr. Windecker said. The 2020 all-virtual conference drew a much younger pool of registrants, on average, than did the live conferences before the pandemic.

“I think that’s an indication of people that may be in training, in early stages of their career, or they don’t have the support from departments or from their practice, or other financial means.” But they are able to participate via computer, tablet, or smartphone, he said.

“Another advantage is that the recorded content can be replayed at the convenience of whoever wants to consume it at a later point in time,” he added. “Those are just some examples why the digital format is likely to stay,” on its own or in a new age of hybrid meetings.  
 

New and updated guidelines

Leading off the guideline series is the document on diagnosis and treatment of acute and chronic HF, which leveraged the past few busy years of HF clinical trials to arrive at a number of new recommendations and strengthened level-of-evidence ratings. It covers both drug and device therapy of HF with reduced ejection fraction (HFrEF) and acute decompensated HF, and tweaks and further enshrines the concept of HF with mildly reduced ejection fraction (HFmrEF).

Several updated recommendations for both long-used and novel medications, notably the sodium-glucose cotransporter 2 inhibitors, will be included because of the recently appreciated evidence-based impact in HFrEF, Dr. Windecker noted.

“I think it will be particularly interesting to look for the SGLT2 inhibitors as not a completely new class of drugs, but certainly one where there has been a lot of new evidence, to look at how those drugs will be integrated in the overall care pathway.”

A top-line preview of the new HF guideline limited to drug therapy, presented at July’s Heart Failure Association of the European Society of Cardiology (ESC-HFA), provided a simple answer to a common question in the new, bountiful age of HFrEF medications: Which meds, initiated in what order?

As it happens, the new recommendation for first-line HFrEF drug therapy is not a silver bullet, but a shotgun – prompt initiation of at least four meds, one from each of four drug classes: renin-angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRA), and SGLT2 inhibitors. Each class, as described in the document, is to be started as soon as safely feasible, in a sequence deemed appropriate for each individual patient.
 

Spotlight on EMPEROR-Preserved

The world already knows that the trial, which tested the SGLT2 inhibitor empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) on top of standard therapy, “met” its primary endpoint in almost 6,000 patients with HF with preserved ejection fraction (HFpEF), who included some with HFmrEF by more contemporary definitions.

That means patients in EMPEROR-Preserved assigned to take empagliflozin showed significantly fewer events that made up the study’s primary endpoint, a composite of CV death or HF hospitalization. It appears to be the first clearly significant overall medical therapy benefit for a clinical primary endpoint in a major randomized HFpEF drug trial.

And that, pending fuller presentation of trial results at the Congress on Aug. 27, could be a huge deal for the half of HF patients with left ventricular ejection fractions (LVEF) higher than the HFrEF range.

Those early top-line results weren’t a decisive bombshell for a field now filled with hope for a practice-changing empagliflozin outcome in EMPEROR-Preserved, which isn’t a certainty. They were more like the “boom” of a mortar launching a rocket of fireworks that may explode into a chrysanthemum or green comet or, sometimes, turn out to be no more than a dud. The promise of the early cursory results critically depends on further details.

“Provided there is a compelling benefit, this is what everyone has been waiting for in this condition for decades,” Mikhail N. Kosiborod, MD, director of cardiometabolic research at Saint Luke’s Mid-America Heart Institute, Kansas City, Mo., said.

“Already knowing that the trial met the primary endpoint is obviously very intriguing and encouraging,” he added. “But there are things we don’t know, such as: What is the magnitude of benefit? And whether that benefit, whatever the magnitude, is driven by reductions in both heart failure hospitalizations and cardiovascular death, or only one of the two.”

For example: “If we see an impressive benefit for reduction of hospitalizations, but not a significant reduction in death, that would still be a huge advance. That’s because, to date, we don’t have any drug for HFpEF that has convincingly demonstrated a compelling reduction in heart failure hospitalization or improvement in symptoms, function, or quality of life,” observed Dr. Kosiborod, who wasn’t part of EMPEROR-Preserved.

There have been “suggestions” from HFrEF trials that empagliflozin and dapagliflozin (Farxiga, AstraZeneca) “have very comparable effects on at least the endpoint of cardiovascular death or hospitalization for heart failure,” he said. “So, my expectation would be that whatever is observed in EMPEROR-Preserved is likely a class effect, as well.”

Following EMPEROR-Preserved on the agenda is EMPEROR-Pooled, a patient-level combined analysis of the EMPEROR series of trials that spans the range of HF, regardless of ejection fraction or diabetes status, primarily exploring the effects of empagliflozin on renal function.
 

Other offerings, Friday, Aug. 27

Scheduled immediately after EMPEROR-Preserved is a presentation on the SMART-MI trial, which should clarify whether management guided by continuous ambulatory monitoring is effective in patients considered at especially high arrhythmic risk. Entry called for recent myocardial infarction and an LVEF of 36%-50% with evidence of cardiac autonomic dysfunction.

The trial randomly assigned 400 such patients to be or not be implanted with a Reveal LINQ (Medtronic) loop recorder and followed them for up to 18 months, primarily for detection of potentially serious arrhythmic events. Endpoints that involved mortality, hospitalization or other clinical events were secondary.

In a time slot preceding both SMART-MI and EMPEROR-Preserved, the GUIDE-HF trial is following a projected 3,600 patients with HF implanted with a CardioMEMS HF System (Abbott) pulmonary artery (PA) pressure sensor to explore the its value for guiding management.

The trial’s three cohorts, followed for at least 12 months, include randomized sensor-monitored and control groups of patients with New York Heart Association class 2-4 symptoms, as well as a third observational set of patients in NYHA class 3. That’s the indication for which the CardioMEMS monitor gained approval in the United States in 2014 based on the 2011 CHAMPION trial, and which fared just as well in the 2017 CHAMPION Post-Approval Study.

The Friday Hot Lines also include Dal-GenE, which has entered about 6,000 patients with recent MI to test the once-abandoned cholesterol ester transfer protein (CETP) inhibitor dalcetrapib (DalCor) for any secondary-prevention benefits when used selectively. The trial’s hook: All its patients are confirmed to have the AA genotype of the rs1967309 variant in the ADCY9 gene, which has been associated with a pronounced clinical response to CETP inhibition.

Saturday, Aug. 28

The direct oral anticoagulants (DOACs) have largely replaced vitamin K antagonists in patients with nonvalvular atrial fibrillation (AFib). But whether DOACs are similarly preferable in the growing world population of people who have undergone transcatheter aortic valve replacement (TAVR or TAVI), an issue explored with variable results in the ATLANTIS and GALILEO trials, is far from settled.

The ENVISAGE-TAVI AF trial explored the question for the factor X inhibitor edoxaban (Savaysa, Lixiana, Daiichi-Sankyo) in 1,400 patients with AFib and a transfemoral TAVR in the previous 5 days, who were randomly assigned to the DOAC or standard management along with discretionary antiplatelet therapy. They’ve been followed for up to 3 years for a composite endpoint of clinical events – including death, MI, and stroke – and for major bleeding.

The day will also feature MASTER DAPT, a comparison of two dual-antiplatelet therapy (DAPT) regimens in an estimated 4,300 patients considered to be high-risk for bleeding who had received the sirolimus-eluting Ultimaster (Terumo) coronary stent, which has a bioresorbable polymer coating.

Investigators have randomly assigned patients to receive either very-short-duration DAPT, for about a month after stenting, followed by a P2Y12 inhibitor alone for up to a year after the procedure; or a more conventional regimen of a P2Y12 inhibitor for 6-12 months with aspirin maintained for a total of 12 months.

Later that day, investigators from the FIGARO-DKD trial will present their results based on 7,437 patients with type 2 diabetes and chronic kidney disease (CKD), a much fuller version than the top-line findings announced by sponsor Bayer 3 months ago.

Those top-line results suggested that patients assigned to receive the nonsteroidal nonselective mineralocorticoid receptor antagonist (MRA) finerenone (Kerendia) on top of standard care benefited with a drop in risk for the primary endpoint of CV death or nonfatal CV events.

Finerenone was recently approved in the United States for treating patients with both type 2 diabetes and CKD based on the published FIDELIO-DKD trial, which had seen less CKD progression and fewer CV events in such patients who took the novel MRA.

Although similar in design to FIGARO-DKD, FIDELIO-DKD had entered fewer patients with early-stage diabetic kidney disease (DKD). That led researchers to pool the two trials’ populations to create a cohort that spans the spectrum of DKD severity. An analysis of the pooled cohort, dubbed FIDELITY, is on the schedule after FIGARO-DKD.

After FIDELITY is the prospective APAF-CRT trial that is following a projected 1,830 patients with permanent, symptomatic AFib and a recent hospitalization for AFib or HF and who were not good candidates for standard ablation. They were assigned to receive either atrioventricular junctional ablation followed by CRT, with or without a defibrillation, on top of optimal meds – a so-called “ablate-and-pace” strategy – or an implantable cardioverter defibrillator with rate-control drug therapy.

The new analysis represents the trial’s second phase in which mortality was followed for 4 years as the primary endpoint, in contrast to the previously reported initial phase that followed the first 102 patients for 2 years for the composite primary endpoint of death, worsening HF, and HF hospitalization. The first phase had halted enrollment before reaching its planned target of 280 patients after an interim analysis showed a significant benefit for ablate and pace. 

Next up: DECAAF 2, a randomized assessment of whether catheter ablation for AFib guided by delayed gadolinium enhancement on MRI, a proxy for scar tissue, can be more effective than standard AFib ablation by pulmonary vein isolation alone. An estimated 900 patients with persistent AFib who had never before undergone ablation for the arrhythmia were randomly assigned to one strategy or the other and followed for AFib recurrence over 18 months.
 

Sunday, Aug. 29

The TOMAHAWK trial aimed to clarify the optimal timing of invasive coronary angiography for resuscitated patients with non–ST-segment elevation out-of-hospital cardiac arrest, a broad population in a setting for which there is little randomized-trial guidance. Investigators randomly assigned 558 such patients to undergo immediate invasive angiography or to direct intensive care unit admission for initial standard care with discretionary delayed angiography. Patients were followed for all-cause mortality, with other clinical events and neurologic outcomes as secondary endpoints.

Next on the schedule, the RIPCORD-2 trial randomly assigned 1,100 patients with stable known or suspected coronary artery disease (CAD) to undergo conventional angiography alone or with added direct pressure-wire measurement of fractional flow reserve to guide management decisions. Primary outcomes include health care costs and patient-reported quality of life at 1 year.

Slated for later that day, the Asymptomatic Carotid Surgery Trial-2 (ACST-2) has entered an estimated 3600 patients with a substantial carotid artery narrowing not associated with symptoms but for which either carotid endarterectomy (CEA) or carotid artery stenting (CAS) was considered anatomically feasible. There also must have been “substantial uncertainty” regarding the optimal procedure choice.

The trial, conducted in 40 countries primarily in Europe and North America and launched in 2008, randomly assigned the patients to undergo either CEA or CAS, in both cases with appropriate medical therapy, and followed them for periprocedural events and up to 10 years for strokes and stroke-related events.

The LOOP study, which is to directly follow ACST-2, has explored whether screening for AFib using the Medtronic Reveal LINQ monitor in older patients with non-AFib stroke risk factors – with oral anticoagulation prescribed for those who test positive – can lower their risk for stroke or systemic embolism. It randomly assigned 6,000 such patients to care guided by the loop recorder or to standard care.

On a somewhat larger scale, the Salt Substitute and Stroke Study (SSaSS) randomly assigned a total of 20,996 people in about 600 villages across northern China and Tibet to sodium-restriction intervention and control groups by village. All participants had a history of stroke or were aged at least 60 years with uncontrolled hypertension.

As described by the trial’s online portal, participants in villages assigned to the intervention group were given a supply of a low-sodium, potassium-supplementing salt substitute to replace their own salt supplies, along with education on the health benefits of sodium restriction. Participants in control villages continued their normal diets and, at the trial’s beginning, received “advice to reduce their salt intake.” All were required to own a telephone.

Clinical events, including strokes and hospitalizations throughout a 5-year follow-up, were tracked by phone calls made to all participants every 6 months and were documented at follow-up home visits.

Sunday is also to feature a Late-Breaking Trials session with a focus on COVID-19, which leads off with COLCOVID, a test of colchicine in patients hospitalized for suspected SARS-CoV-2 infection and in acute respiratory distress.

The 1,279 participants in Argentina were randomly assigned to receive or not receive the potent anti-inflammatory agent on top of antivirals and other standard management and followed for death or new need for mechanical ventilation. A successful outcome would contrast with the RECOVERY trial, which terminated a colchicine group of patients hospitalized with COVID-19 because of a lack of efficacy earlier this year.

COLCOVID is to be followed by the MICHELLE trial of rivaroxaban (Xarelto, Bayer/Janssen) prophylaxis, compared with no preventive oral anticoagulant, in 320 patients who, when hospitalized with COVID-19, had been on parenteral anticoagulants because of an elevated risk for venous thromboembolism. The trial, conducted in Brazil, called for postdischarge rivaroxaban at a once-daily dosage of 10 mg for about 1 month.

The session also includes a presentation called “Insights into the Effects of the COVID-19 Pandemic: Comprehensive Analysis from the GUIDE-HF Trial,” the primary outcomes of which will be reported on the first day of the Congress.

Following is a presentation on the PREPARE-IT study of icosapent ethyl (Vascepa, Amarin), given at high dosages intended to be anti-inflammatory, compared with placebo, in an estimated 4,000 adults. The trial has two groups: A prevention group of adults living and circulating in the community; and a treatment group of patients aged at least 40 years with confirmed symptomatic SARS-CoV-2 infection for whom the need for hospitalization isn’t clear.
 

Monday, Aug. 30

The final day of the Congress features a trial called Influenza Vaccination after Myocardial Infarction (IAMI), which has tested the secondary preventive effect of influenza vaccination by randomly assigning 2,571 patients to receive a standard vaccine or a saline placebo injection on one occasion.

Entry to the international trial called for a diagnosis of MI with or without ST-segment elevation, or stable CAD and age at least 75 years with other risk factors. The patients were followed for death, MI, stent thrombosis, and a slew of secondary endpoints over 12 months.

Monday offerings continue later in a time block leading off with the STEP trial, which has randomly assigned an estimated 8,000 patients at 40 centers in China who are 60 to 80 years of age with a systolic blood pressure of 140 to <190 mm Hg to be on standard guideline-based therapy or an intensive drug-management strategy.

The systolic BP goals are 130 to <150 mm Hg for standard care and 110 to <130 mm Hg for the intensive regimen. The composite primary endpoint includes death and clinical events related to acute coronary syndromes, HF, revascularization, and stroke.

Following on heels of STEP, the Amulet IDE trial – the first major randomized comparison of two transcatheter LAA closure devices – entered 1,878 patients with nonvalvular AFib who were considered high-risk for bleeding and stroke or systemic embolism.

They were randomly assigned in the noninferiority trial to receive either the AMPLATZER Amulet (Abbott Medical Devices) or the WATCHMAN (Boston Scientific) closure devices and were followed for safety and efficacy for up to 5 years.

Both LAA closure devices, intended to make patients with AFib less reliant on oral anticoagulation, are now available on both sides of the Atlantic – as well as many other countries – after the Amulet’s United States market approval on Aug. 16, based largely on the Amulet IDE trial.

Rounding out the final Hot Line set is one of the latest efforts to show the efficacy and safety of a very short DAPT period after coronary stenting in patients with acute coronary syndromes, the STOPDAPT-2 ACS trial.

The study assigned 3,008 patients in Japan to receive aspirin and clopidogrel for either 1 month or 1 year after implantation with an everolimus-eluting cobalt-chromium stent and followed them for up to 5 years for a composite of MI, CV death, stent thrombosis, stroke, and bleeding.

The trial follows the published STOPDAPT-2 trial that showed superiority for the 1-month DAPT regimen in a predominantly stable-CAD population treated with the same kind of stent.
 

Program structure and format

A total of 15 online channels are to be available in the morning, European time, their schedules running in parallel. Presentations often are prerecorded, but also include live sessions at 8:00 a.m. Central time and 12 p.m. CET (2:00 a.m. and 6:00 a.m. Eastern time) to liven up the channel offerings, Dr. Windecker observed, and to make them more immediate and potentially interactive.

Many of the parallel channels are devoted throughout the Congress to particular silos of cardiology; for example, arrhythmias and device therapy is on channel 3; CAD and acute care is on 5; HF is on 6; and preventive cardiology is on 9.

Other channels swing across different topics from day to day, such as channel 1, which covers COVID-19 topics on the first and third day of the meeting, “advances in science” on day 2, and “digital health, public health, health economics” on day 4.

The focus each day, starting at 2:00 p.m. CET (8:00 a.m. ET) and continuing into the evening in Europe, shifts over to the Prime Time live program, which features the Hot Line and guideline presentations and many of the live abstract presentations.

Dr. Kosiborod, not a researcher with the EMPEROR trials, is chair of the Dapagliflozin in Preserved Ejection Fraction Heart Failure ( PRESERVED-HF ) trial, which is scheduled for presentation at the September 2021 Heart Failure Society of American meeting.

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

There will be so much more to the annual congress of the European Society of Cardiology, which begins Aug. 27 with an all-virtual format, than detailed primary results of EMPEROR-Preserved, a trial that could mark a turning point for heart failure (HF) medical therapy.

Also among the featured Hot Line and Late-Breaking Science sessions are – along with many other studies – explorations of arrhythmia management (ablation or guided by loop recorder); secondary prevention, including by vaccination; oral anticoagulation, notably after transcatheter valve procedures; and colchicine or thrombosis prophylaxis in hospitalized patients with COVID-19.

There will even be a head-to-head comparison of two long-familiar left atrial appendage (LAA) occluders, and a population-based, randomized trial of sodium restriction through wide-scale use of a potassium-based salt substitute.

The congress will also introduce four guideline documents at sessions throughout the Congress, one on each day. They cover new and modified recommendations for heart failure; pacing, including cardiac resynchronization therapy (CRT); cardiovascular (CV) disease prevention; and, with cosponsorship from the European Association for Cardio-Thoracic Surgery, valvular heart disease.
 

The virtues of virtual

That next year’s Congress is slated for Aug. 27-30 in Barcelona should be welcome news for anyone whose “what if” curiosity about all-virtual conferences has already been satisfied. But with experience comes wisdom, as the medical societies have learned that online scientific meetings have some winning qualities that may be worth keeping, as least for a while.

“I think there is no doubt that the digital format will continue, for several reasons. One is that this pandemic is not over,” ESC Congress program committee chair Stephan Windecker, MD, Bern (Switzerland) University Hospital, , told this news organization. “As long as it is not over, the digital format is here to stay.”

But it also appears that people who haven’t been able to attend the congress in person are keen to log in and engage online, Dr. Windecker said. The 2020 all-virtual conference drew a much younger pool of registrants, on average, than did the live conferences before the pandemic.

“I think that’s an indication of people that may be in training, in early stages of their career, or they don’t have the support from departments or from their practice, or other financial means.” But they are able to participate via computer, tablet, or smartphone, he said.

“Another advantage is that the recorded content can be replayed at the convenience of whoever wants to consume it at a later point in time,” he added. “Those are just some examples why the digital format is likely to stay,” on its own or in a new age of hybrid meetings.  
 

New and updated guidelines

Leading off the guideline series is the document on diagnosis and treatment of acute and chronic HF, which leveraged the past few busy years of HF clinical trials to arrive at a number of new recommendations and strengthened level-of-evidence ratings. It covers both drug and device therapy of HF with reduced ejection fraction (HFrEF) and acute decompensated HF, and tweaks and further enshrines the concept of HF with mildly reduced ejection fraction (HFmrEF).

Several updated recommendations for both long-used and novel medications, notably the sodium-glucose cotransporter 2 inhibitors, will be included because of the recently appreciated evidence-based impact in HFrEF, Dr. Windecker noted.

“I think it will be particularly interesting to look for the SGLT2 inhibitors as not a completely new class of drugs, but certainly one where there has been a lot of new evidence, to look at how those drugs will be integrated in the overall care pathway.”

A top-line preview of the new HF guideline limited to drug therapy, presented at July’s Heart Failure Association of the European Society of Cardiology (ESC-HFA), provided a simple answer to a common question in the new, bountiful age of HFrEF medications: Which meds, initiated in what order?

As it happens, the new recommendation for first-line HFrEF drug therapy is not a silver bullet, but a shotgun – prompt initiation of at least four meds, one from each of four drug classes: renin-angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRA), and SGLT2 inhibitors. Each class, as described in the document, is to be started as soon as safely feasible, in a sequence deemed appropriate for each individual patient.
 

Spotlight on EMPEROR-Preserved

The world already knows that the trial, which tested the SGLT2 inhibitor empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) on top of standard therapy, “met” its primary endpoint in almost 6,000 patients with HF with preserved ejection fraction (HFpEF), who included some with HFmrEF by more contemporary definitions.

That means patients in EMPEROR-Preserved assigned to take empagliflozin showed significantly fewer events that made up the study’s primary endpoint, a composite of CV death or HF hospitalization. It appears to be the first clearly significant overall medical therapy benefit for a clinical primary endpoint in a major randomized HFpEF drug trial.

And that, pending fuller presentation of trial results at the Congress on Aug. 27, could be a huge deal for the half of HF patients with left ventricular ejection fractions (LVEF) higher than the HFrEF range.

Those early top-line results weren’t a decisive bombshell for a field now filled with hope for a practice-changing empagliflozin outcome in EMPEROR-Preserved, which isn’t a certainty. They were more like the “boom” of a mortar launching a rocket of fireworks that may explode into a chrysanthemum or green comet or, sometimes, turn out to be no more than a dud. The promise of the early cursory results critically depends on further details.

“Provided there is a compelling benefit, this is what everyone has been waiting for in this condition for decades,” Mikhail N. Kosiborod, MD, director of cardiometabolic research at Saint Luke’s Mid-America Heart Institute, Kansas City, Mo., said.

“Already knowing that the trial met the primary endpoint is obviously very intriguing and encouraging,” he added. “But there are things we don’t know, such as: What is the magnitude of benefit? And whether that benefit, whatever the magnitude, is driven by reductions in both heart failure hospitalizations and cardiovascular death, or only one of the two.”

For example: “If we see an impressive benefit for reduction of hospitalizations, but not a significant reduction in death, that would still be a huge advance. That’s because, to date, we don’t have any drug for HFpEF that has convincingly demonstrated a compelling reduction in heart failure hospitalization or improvement in symptoms, function, or quality of life,” observed Dr. Kosiborod, who wasn’t part of EMPEROR-Preserved.

There have been “suggestions” from HFrEF trials that empagliflozin and dapagliflozin (Farxiga, AstraZeneca) “have very comparable effects on at least the endpoint of cardiovascular death or hospitalization for heart failure,” he said. “So, my expectation would be that whatever is observed in EMPEROR-Preserved is likely a class effect, as well.”

Following EMPEROR-Preserved on the agenda is EMPEROR-Pooled, a patient-level combined analysis of the EMPEROR series of trials that spans the range of HF, regardless of ejection fraction or diabetes status, primarily exploring the effects of empagliflozin on renal function.
 

Other offerings, Friday, Aug. 27

Scheduled immediately after EMPEROR-Preserved is a presentation on the SMART-MI trial, which should clarify whether management guided by continuous ambulatory monitoring is effective in patients considered at especially high arrhythmic risk. Entry called for recent myocardial infarction and an LVEF of 36%-50% with evidence of cardiac autonomic dysfunction.

The trial randomly assigned 400 such patients to be or not be implanted with a Reveal LINQ (Medtronic) loop recorder and followed them for up to 18 months, primarily for detection of potentially serious arrhythmic events. Endpoints that involved mortality, hospitalization or other clinical events were secondary.

In a time slot preceding both SMART-MI and EMPEROR-Preserved, the GUIDE-HF trial is following a projected 3,600 patients with HF implanted with a CardioMEMS HF System (Abbott) pulmonary artery (PA) pressure sensor to explore the its value for guiding management.

The trial’s three cohorts, followed for at least 12 months, include randomized sensor-monitored and control groups of patients with New York Heart Association class 2-4 symptoms, as well as a third observational set of patients in NYHA class 3. That’s the indication for which the CardioMEMS monitor gained approval in the United States in 2014 based on the 2011 CHAMPION trial, and which fared just as well in the 2017 CHAMPION Post-Approval Study.

The Friday Hot Lines also include Dal-GenE, which has entered about 6,000 patients with recent MI to test the once-abandoned cholesterol ester transfer protein (CETP) inhibitor dalcetrapib (DalCor) for any secondary-prevention benefits when used selectively. The trial’s hook: All its patients are confirmed to have the AA genotype of the rs1967309 variant in the ADCY9 gene, which has been associated with a pronounced clinical response to CETP inhibition.

Saturday, Aug. 28

The direct oral anticoagulants (DOACs) have largely replaced vitamin K antagonists in patients with nonvalvular atrial fibrillation (AFib). But whether DOACs are similarly preferable in the growing world population of people who have undergone transcatheter aortic valve replacement (TAVR or TAVI), an issue explored with variable results in the ATLANTIS and GALILEO trials, is far from settled.

The ENVISAGE-TAVI AF trial explored the question for the factor X inhibitor edoxaban (Savaysa, Lixiana, Daiichi-Sankyo) in 1,400 patients with AFib and a transfemoral TAVR in the previous 5 days, who were randomly assigned to the DOAC or standard management along with discretionary antiplatelet therapy. They’ve been followed for up to 3 years for a composite endpoint of clinical events – including death, MI, and stroke – and for major bleeding.

The day will also feature MASTER DAPT, a comparison of two dual-antiplatelet therapy (DAPT) regimens in an estimated 4,300 patients considered to be high-risk for bleeding who had received the sirolimus-eluting Ultimaster (Terumo) coronary stent, which has a bioresorbable polymer coating.

Investigators have randomly assigned patients to receive either very-short-duration DAPT, for about a month after stenting, followed by a P2Y12 inhibitor alone for up to a year after the procedure; or a more conventional regimen of a P2Y12 inhibitor for 6-12 months with aspirin maintained for a total of 12 months.

Later that day, investigators from the FIGARO-DKD trial will present their results based on 7,437 patients with type 2 diabetes and chronic kidney disease (CKD), a much fuller version than the top-line findings announced by sponsor Bayer 3 months ago.

Those top-line results suggested that patients assigned to receive the nonsteroidal nonselective mineralocorticoid receptor antagonist (MRA) finerenone (Kerendia) on top of standard care benefited with a drop in risk for the primary endpoint of CV death or nonfatal CV events.

Finerenone was recently approved in the United States for treating patients with both type 2 diabetes and CKD based on the published FIDELIO-DKD trial, which had seen less CKD progression and fewer CV events in such patients who took the novel MRA.

Although similar in design to FIGARO-DKD, FIDELIO-DKD had entered fewer patients with early-stage diabetic kidney disease (DKD). That led researchers to pool the two trials’ populations to create a cohort that spans the spectrum of DKD severity. An analysis of the pooled cohort, dubbed FIDELITY, is on the schedule after FIGARO-DKD.

After FIDELITY is the prospective APAF-CRT trial that is following a projected 1,830 patients with permanent, symptomatic AFib and a recent hospitalization for AFib or HF and who were not good candidates for standard ablation. They were assigned to receive either atrioventricular junctional ablation followed by CRT, with or without a defibrillation, on top of optimal meds – a so-called “ablate-and-pace” strategy – or an implantable cardioverter defibrillator with rate-control drug therapy.

The new analysis represents the trial’s second phase in which mortality was followed for 4 years as the primary endpoint, in contrast to the previously reported initial phase that followed the first 102 patients for 2 years for the composite primary endpoint of death, worsening HF, and HF hospitalization. The first phase had halted enrollment before reaching its planned target of 280 patients after an interim analysis showed a significant benefit for ablate and pace. 

Next up: DECAAF 2, a randomized assessment of whether catheter ablation for AFib guided by delayed gadolinium enhancement on MRI, a proxy for scar tissue, can be more effective than standard AFib ablation by pulmonary vein isolation alone. An estimated 900 patients with persistent AFib who had never before undergone ablation for the arrhythmia were randomly assigned to one strategy or the other and followed for AFib recurrence over 18 months.
 

Sunday, Aug. 29

The TOMAHAWK trial aimed to clarify the optimal timing of invasive coronary angiography for resuscitated patients with non–ST-segment elevation out-of-hospital cardiac arrest, a broad population in a setting for which there is little randomized-trial guidance. Investigators randomly assigned 558 such patients to undergo immediate invasive angiography or to direct intensive care unit admission for initial standard care with discretionary delayed angiography. Patients were followed for all-cause mortality, with other clinical events and neurologic outcomes as secondary endpoints.

Next on the schedule, the RIPCORD-2 trial randomly assigned 1,100 patients with stable known or suspected coronary artery disease (CAD) to undergo conventional angiography alone or with added direct pressure-wire measurement of fractional flow reserve to guide management decisions. Primary outcomes include health care costs and patient-reported quality of life at 1 year.

Slated for later that day, the Asymptomatic Carotid Surgery Trial-2 (ACST-2) has entered an estimated 3600 patients with a substantial carotid artery narrowing not associated with symptoms but for which either carotid endarterectomy (CEA) or carotid artery stenting (CAS) was considered anatomically feasible. There also must have been “substantial uncertainty” regarding the optimal procedure choice.

The trial, conducted in 40 countries primarily in Europe and North America and launched in 2008, randomly assigned the patients to undergo either CEA or CAS, in both cases with appropriate medical therapy, and followed them for periprocedural events and up to 10 years for strokes and stroke-related events.

The LOOP study, which is to directly follow ACST-2, has explored whether screening for AFib using the Medtronic Reveal LINQ monitor in older patients with non-AFib stroke risk factors – with oral anticoagulation prescribed for those who test positive – can lower their risk for stroke or systemic embolism. It randomly assigned 6,000 such patients to care guided by the loop recorder or to standard care.

On a somewhat larger scale, the Salt Substitute and Stroke Study (SSaSS) randomly assigned a total of 20,996 people in about 600 villages across northern China and Tibet to sodium-restriction intervention and control groups by village. All participants had a history of stroke or were aged at least 60 years with uncontrolled hypertension.

As described by the trial’s online portal, participants in villages assigned to the intervention group were given a supply of a low-sodium, potassium-supplementing salt substitute to replace their own salt supplies, along with education on the health benefits of sodium restriction. Participants in control villages continued their normal diets and, at the trial’s beginning, received “advice to reduce their salt intake.” All were required to own a telephone.

Clinical events, including strokes and hospitalizations throughout a 5-year follow-up, were tracked by phone calls made to all participants every 6 months and were documented at follow-up home visits.

Sunday is also to feature a Late-Breaking Trials session with a focus on COVID-19, which leads off with COLCOVID, a test of colchicine in patients hospitalized for suspected SARS-CoV-2 infection and in acute respiratory distress.

The 1,279 participants in Argentina were randomly assigned to receive or not receive the potent anti-inflammatory agent on top of antivirals and other standard management and followed for death or new need for mechanical ventilation. A successful outcome would contrast with the RECOVERY trial, which terminated a colchicine group of patients hospitalized with COVID-19 because of a lack of efficacy earlier this year.

COLCOVID is to be followed by the MICHELLE trial of rivaroxaban (Xarelto, Bayer/Janssen) prophylaxis, compared with no preventive oral anticoagulant, in 320 patients who, when hospitalized with COVID-19, had been on parenteral anticoagulants because of an elevated risk for venous thromboembolism. The trial, conducted in Brazil, called for postdischarge rivaroxaban at a once-daily dosage of 10 mg for about 1 month.

The session also includes a presentation called “Insights into the Effects of the COVID-19 Pandemic: Comprehensive Analysis from the GUIDE-HF Trial,” the primary outcomes of which will be reported on the first day of the Congress.

Following is a presentation on the PREPARE-IT study of icosapent ethyl (Vascepa, Amarin), given at high dosages intended to be anti-inflammatory, compared with placebo, in an estimated 4,000 adults. The trial has two groups: A prevention group of adults living and circulating in the community; and a treatment group of patients aged at least 40 years with confirmed symptomatic SARS-CoV-2 infection for whom the need for hospitalization isn’t clear.
 

Monday, Aug. 30

The final day of the Congress features a trial called Influenza Vaccination after Myocardial Infarction (IAMI), which has tested the secondary preventive effect of influenza vaccination by randomly assigning 2,571 patients to receive a standard vaccine or a saline placebo injection on one occasion.

Entry to the international trial called for a diagnosis of MI with or without ST-segment elevation, or stable CAD and age at least 75 years with other risk factors. The patients were followed for death, MI, stent thrombosis, and a slew of secondary endpoints over 12 months.

Monday offerings continue later in a time block leading off with the STEP trial, which has randomly assigned an estimated 8,000 patients at 40 centers in China who are 60 to 80 years of age with a systolic blood pressure of 140 to <190 mm Hg to be on standard guideline-based therapy or an intensive drug-management strategy.

The systolic BP goals are 130 to <150 mm Hg for standard care and 110 to <130 mm Hg for the intensive regimen. The composite primary endpoint includes death and clinical events related to acute coronary syndromes, HF, revascularization, and stroke.

Following on heels of STEP, the Amulet IDE trial – the first major randomized comparison of two transcatheter LAA closure devices – entered 1,878 patients with nonvalvular AFib who were considered high-risk for bleeding and stroke or systemic embolism.

They were randomly assigned in the noninferiority trial to receive either the AMPLATZER Amulet (Abbott Medical Devices) or the WATCHMAN (Boston Scientific) closure devices and were followed for safety and efficacy for up to 5 years.

Both LAA closure devices, intended to make patients with AFib less reliant on oral anticoagulation, are now available on both sides of the Atlantic – as well as many other countries – after the Amulet’s United States market approval on Aug. 16, based largely on the Amulet IDE trial.

Rounding out the final Hot Line set is one of the latest efforts to show the efficacy and safety of a very short DAPT period after coronary stenting in patients with acute coronary syndromes, the STOPDAPT-2 ACS trial.

The study assigned 3,008 patients in Japan to receive aspirin and clopidogrel for either 1 month or 1 year after implantation with an everolimus-eluting cobalt-chromium stent and followed them for up to 5 years for a composite of MI, CV death, stent thrombosis, stroke, and bleeding.

The trial follows the published STOPDAPT-2 trial that showed superiority for the 1-month DAPT regimen in a predominantly stable-CAD population treated with the same kind of stent.
 

Program structure and format

A total of 15 online channels are to be available in the morning, European time, their schedules running in parallel. Presentations often are prerecorded, but also include live sessions at 8:00 a.m. Central time and 12 p.m. CET (2:00 a.m. and 6:00 a.m. Eastern time) to liven up the channel offerings, Dr. Windecker observed, and to make them more immediate and potentially interactive.

Many of the parallel channels are devoted throughout the Congress to particular silos of cardiology; for example, arrhythmias and device therapy is on channel 3; CAD and acute care is on 5; HF is on 6; and preventive cardiology is on 9.

Other channels swing across different topics from day to day, such as channel 1, which covers COVID-19 topics on the first and third day of the meeting, “advances in science” on day 2, and “digital health, public health, health economics” on day 4.

The focus each day, starting at 2:00 p.m. CET (8:00 a.m. ET) and continuing into the evening in Europe, shifts over to the Prime Time live program, which features the Hot Line and guideline presentations and many of the live abstract presentations.

Dr. Kosiborod, not a researcher with the EMPEROR trials, is chair of the Dapagliflozin in Preserved Ejection Fraction Heart Failure ( PRESERVED-HF ) trial, which is scheduled for presentation at the September 2021 Heart Failure Society of American meeting.

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

There will be so much more to the annual congress of the European Society of Cardiology, which begins Aug. 27 with an all-virtual format, than detailed primary results of EMPEROR-Preserved, a trial that could mark a turning point for heart failure (HF) medical therapy.

Also among the featured Hot Line and Late-Breaking Science sessions are – along with many other studies – explorations of arrhythmia management (ablation or guided by loop recorder); secondary prevention, including by vaccination; oral anticoagulation, notably after transcatheter valve procedures; and colchicine or thrombosis prophylaxis in hospitalized patients with COVID-19.

There will even be a head-to-head comparison of two long-familiar left atrial appendage (LAA) occluders, and a population-based, randomized trial of sodium restriction through wide-scale use of a potassium-based salt substitute.

The congress will also introduce four guideline documents at sessions throughout the Congress, one on each day. They cover new and modified recommendations for heart failure; pacing, including cardiac resynchronization therapy (CRT); cardiovascular (CV) disease prevention; and, with cosponsorship from the European Association for Cardio-Thoracic Surgery, valvular heart disease.
 

The virtues of virtual

That next year’s Congress is slated for Aug. 27-30 in Barcelona should be welcome news for anyone whose “what if” curiosity about all-virtual conferences has already been satisfied. But with experience comes wisdom, as the medical societies have learned that online scientific meetings have some winning qualities that may be worth keeping, as least for a while.

“I think there is no doubt that the digital format will continue, for several reasons. One is that this pandemic is not over,” ESC Congress program committee chair Stephan Windecker, MD, Bern (Switzerland) University Hospital, , told this news organization. “As long as it is not over, the digital format is here to stay.”

But it also appears that people who haven’t been able to attend the congress in person are keen to log in and engage online, Dr. Windecker said. The 2020 all-virtual conference drew a much younger pool of registrants, on average, than did the live conferences before the pandemic.

“I think that’s an indication of people that may be in training, in early stages of their career, or they don’t have the support from departments or from their practice, or other financial means.” But they are able to participate via computer, tablet, or smartphone, he said.

“Another advantage is that the recorded content can be replayed at the convenience of whoever wants to consume it at a later point in time,” he added. “Those are just some examples why the digital format is likely to stay,” on its own or in a new age of hybrid meetings.  
 

New and updated guidelines

Leading off the guideline series is the document on diagnosis and treatment of acute and chronic HF, which leveraged the past few busy years of HF clinical trials to arrive at a number of new recommendations and strengthened level-of-evidence ratings. It covers both drug and device therapy of HF with reduced ejection fraction (HFrEF) and acute decompensated HF, and tweaks and further enshrines the concept of HF with mildly reduced ejection fraction (HFmrEF).

Several updated recommendations for both long-used and novel medications, notably the sodium-glucose cotransporter 2 inhibitors, will be included because of the recently appreciated evidence-based impact in HFrEF, Dr. Windecker noted.

“I think it will be particularly interesting to look for the SGLT2 inhibitors as not a completely new class of drugs, but certainly one where there has been a lot of new evidence, to look at how those drugs will be integrated in the overall care pathway.”

A top-line preview of the new HF guideline limited to drug therapy, presented at July’s Heart Failure Association of the European Society of Cardiology (ESC-HFA), provided a simple answer to a common question in the new, bountiful age of HFrEF medications: Which meds, initiated in what order?

As it happens, the new recommendation for first-line HFrEF drug therapy is not a silver bullet, but a shotgun – prompt initiation of at least four meds, one from each of four drug classes: renin-angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRA), and SGLT2 inhibitors. Each class, as described in the document, is to be started as soon as safely feasible, in a sequence deemed appropriate for each individual patient.
 

Spotlight on EMPEROR-Preserved

The world already knows that the trial, which tested the SGLT2 inhibitor empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) on top of standard therapy, “met” its primary endpoint in almost 6,000 patients with HF with preserved ejection fraction (HFpEF), who included some with HFmrEF by more contemporary definitions.

That means patients in EMPEROR-Preserved assigned to take empagliflozin showed significantly fewer events that made up the study’s primary endpoint, a composite of CV death or HF hospitalization. It appears to be the first clearly significant overall medical therapy benefit for a clinical primary endpoint in a major randomized HFpEF drug trial.

And that, pending fuller presentation of trial results at the Congress on Aug. 27, could be a huge deal for the half of HF patients with left ventricular ejection fractions (LVEF) higher than the HFrEF range.

Those early top-line results weren’t a decisive bombshell for a field now filled with hope for a practice-changing empagliflozin outcome in EMPEROR-Preserved, which isn’t a certainty. They were more like the “boom” of a mortar launching a rocket of fireworks that may explode into a chrysanthemum or green comet or, sometimes, turn out to be no more than a dud. The promise of the early cursory results critically depends on further details.

“Provided there is a compelling benefit, this is what everyone has been waiting for in this condition for decades,” Mikhail N. Kosiborod, MD, director of cardiometabolic research at Saint Luke’s Mid-America Heart Institute, Kansas City, Mo., said.

“Already knowing that the trial met the primary endpoint is obviously very intriguing and encouraging,” he added. “But there are things we don’t know, such as: What is the magnitude of benefit? And whether that benefit, whatever the magnitude, is driven by reductions in both heart failure hospitalizations and cardiovascular death, or only one of the two.”

For example: “If we see an impressive benefit for reduction of hospitalizations, but not a significant reduction in death, that would still be a huge advance. That’s because, to date, we don’t have any drug for HFpEF that has convincingly demonstrated a compelling reduction in heart failure hospitalization or improvement in symptoms, function, or quality of life,” observed Dr. Kosiborod, who wasn’t part of EMPEROR-Preserved.

There have been “suggestions” from HFrEF trials that empagliflozin and dapagliflozin (Farxiga, AstraZeneca) “have very comparable effects on at least the endpoint of cardiovascular death or hospitalization for heart failure,” he said. “So, my expectation would be that whatever is observed in EMPEROR-Preserved is likely a class effect, as well.”

Following EMPEROR-Preserved on the agenda is EMPEROR-Pooled, a patient-level combined analysis of the EMPEROR series of trials that spans the range of HF, regardless of ejection fraction or diabetes status, primarily exploring the effects of empagliflozin on renal function.
 

Other offerings, Friday, Aug. 27

Scheduled immediately after EMPEROR-Preserved is a presentation on the SMART-MI trial, which should clarify whether management guided by continuous ambulatory monitoring is effective in patients considered at especially high arrhythmic risk. Entry called for recent myocardial infarction and an LVEF of 36%-50% with evidence of cardiac autonomic dysfunction.

The trial randomly assigned 400 such patients to be or not be implanted with a Reveal LINQ (Medtronic) loop recorder and followed them for up to 18 months, primarily for detection of potentially serious arrhythmic events. Endpoints that involved mortality, hospitalization or other clinical events were secondary.

In a time slot preceding both SMART-MI and EMPEROR-Preserved, the GUIDE-HF trial is following a projected 3,600 patients with HF implanted with a CardioMEMS HF System (Abbott) pulmonary artery (PA) pressure sensor to explore the its value for guiding management.

The trial’s three cohorts, followed for at least 12 months, include randomized sensor-monitored and control groups of patients with New York Heart Association class 2-4 symptoms, as well as a third observational set of patients in NYHA class 3. That’s the indication for which the CardioMEMS monitor gained approval in the United States in 2014 based on the 2011 CHAMPION trial, and which fared just as well in the 2017 CHAMPION Post-Approval Study.

The Friday Hot Lines also include Dal-GenE, which has entered about 6,000 patients with recent MI to test the once-abandoned cholesterol ester transfer protein (CETP) inhibitor dalcetrapib (DalCor) for any secondary-prevention benefits when used selectively. The trial’s hook: All its patients are confirmed to have the AA genotype of the rs1967309 variant in the ADCY9 gene, which has been associated with a pronounced clinical response to CETP inhibition.

Saturday, Aug. 28

The direct oral anticoagulants (DOACs) have largely replaced vitamin K antagonists in patients with nonvalvular atrial fibrillation (AFib). But whether DOACs are similarly preferable in the growing world population of people who have undergone transcatheter aortic valve replacement (TAVR or TAVI), an issue explored with variable results in the ATLANTIS and GALILEO trials, is far from settled.

The ENVISAGE-TAVI AF trial explored the question for the factor X inhibitor edoxaban (Savaysa, Lixiana, Daiichi-Sankyo) in 1,400 patients with AFib and a transfemoral TAVR in the previous 5 days, who were randomly assigned to the DOAC or standard management along with discretionary antiplatelet therapy. They’ve been followed for up to 3 years for a composite endpoint of clinical events – including death, MI, and stroke – and for major bleeding.

The day will also feature MASTER DAPT, a comparison of two dual-antiplatelet therapy (DAPT) regimens in an estimated 4,300 patients considered to be high-risk for bleeding who had received the sirolimus-eluting Ultimaster (Terumo) coronary stent, which has a bioresorbable polymer coating.

Investigators have randomly assigned patients to receive either very-short-duration DAPT, for about a month after stenting, followed by a P2Y12 inhibitor alone for up to a year after the procedure; or a more conventional regimen of a P2Y12 inhibitor for 6-12 months with aspirin maintained for a total of 12 months.

Later that day, investigators from the FIGARO-DKD trial will present their results based on 7,437 patients with type 2 diabetes and chronic kidney disease (CKD), a much fuller version than the top-line findings announced by sponsor Bayer 3 months ago.

Those top-line results suggested that patients assigned to receive the nonsteroidal nonselective mineralocorticoid receptor antagonist (MRA) finerenone (Kerendia) on top of standard care benefited with a drop in risk for the primary endpoint of CV death or nonfatal CV events.

Finerenone was recently approved in the United States for treating patients with both type 2 diabetes and CKD based on the published FIDELIO-DKD trial, which had seen less CKD progression and fewer CV events in such patients who took the novel MRA.

Although similar in design to FIGARO-DKD, FIDELIO-DKD had entered fewer patients with early-stage diabetic kidney disease (DKD). That led researchers to pool the two trials’ populations to create a cohort that spans the spectrum of DKD severity. An analysis of the pooled cohort, dubbed FIDELITY, is on the schedule after FIGARO-DKD.

After FIDELITY is the prospective APAF-CRT trial that is following a projected 1,830 patients with permanent, symptomatic AFib and a recent hospitalization for AFib or HF and who were not good candidates for standard ablation. They were assigned to receive either atrioventricular junctional ablation followed by CRT, with or without a defibrillation, on top of optimal meds – a so-called “ablate-and-pace” strategy – or an implantable cardioverter defibrillator with rate-control drug therapy.

The new analysis represents the trial’s second phase in which mortality was followed for 4 years as the primary endpoint, in contrast to the previously reported initial phase that followed the first 102 patients for 2 years for the composite primary endpoint of death, worsening HF, and HF hospitalization. The first phase had halted enrollment before reaching its planned target of 280 patients after an interim analysis showed a significant benefit for ablate and pace. 

Next up: DECAAF 2, a randomized assessment of whether catheter ablation for AFib guided by delayed gadolinium enhancement on MRI, a proxy for scar tissue, can be more effective than standard AFib ablation by pulmonary vein isolation alone. An estimated 900 patients with persistent AFib who had never before undergone ablation for the arrhythmia were randomly assigned to one strategy or the other and followed for AFib recurrence over 18 months.
 

Sunday, Aug. 29

The TOMAHAWK trial aimed to clarify the optimal timing of invasive coronary angiography for resuscitated patients with non–ST-segment elevation out-of-hospital cardiac arrest, a broad population in a setting for which there is little randomized-trial guidance. Investigators randomly assigned 558 such patients to undergo immediate invasive angiography or to direct intensive care unit admission for initial standard care with discretionary delayed angiography. Patients were followed for all-cause mortality, with other clinical events and neurologic outcomes as secondary endpoints.

Next on the schedule, the RIPCORD-2 trial randomly assigned 1,100 patients with stable known or suspected coronary artery disease (CAD) to undergo conventional angiography alone or with added direct pressure-wire measurement of fractional flow reserve to guide management decisions. Primary outcomes include health care costs and patient-reported quality of life at 1 year.

Slated for later that day, the Asymptomatic Carotid Surgery Trial-2 (ACST-2) has entered an estimated 3600 patients with a substantial carotid artery narrowing not associated with symptoms but for which either carotid endarterectomy (CEA) or carotid artery stenting (CAS) was considered anatomically feasible. There also must have been “substantial uncertainty” regarding the optimal procedure choice.

The trial, conducted in 40 countries primarily in Europe and North America and launched in 2008, randomly assigned the patients to undergo either CEA or CAS, in both cases with appropriate medical therapy, and followed them for periprocedural events and up to 10 years for strokes and stroke-related events.

The LOOP study, which is to directly follow ACST-2, has explored whether screening for AFib using the Medtronic Reveal LINQ monitor in older patients with non-AFib stroke risk factors – with oral anticoagulation prescribed for those who test positive – can lower their risk for stroke or systemic embolism. It randomly assigned 6,000 such patients to care guided by the loop recorder or to standard care.

On a somewhat larger scale, the Salt Substitute and Stroke Study (SSaSS) randomly assigned a total of 20,996 people in about 600 villages across northern China and Tibet to sodium-restriction intervention and control groups by village. All participants had a history of stroke or were aged at least 60 years with uncontrolled hypertension.

As described by the trial’s online portal, participants in villages assigned to the intervention group were given a supply of a low-sodium, potassium-supplementing salt substitute to replace their own salt supplies, along with education on the health benefits of sodium restriction. Participants in control villages continued their normal diets and, at the trial’s beginning, received “advice to reduce their salt intake.” All were required to own a telephone.

Clinical events, including strokes and hospitalizations throughout a 5-year follow-up, were tracked by phone calls made to all participants every 6 months and were documented at follow-up home visits.

Sunday is also to feature a Late-Breaking Trials session with a focus on COVID-19, which leads off with COLCOVID, a test of colchicine in patients hospitalized for suspected SARS-CoV-2 infection and in acute respiratory distress.

The 1,279 participants in Argentina were randomly assigned to receive or not receive the potent anti-inflammatory agent on top of antivirals and other standard management and followed for death or new need for mechanical ventilation. A successful outcome would contrast with the RECOVERY trial, which terminated a colchicine group of patients hospitalized with COVID-19 because of a lack of efficacy earlier this year.

COLCOVID is to be followed by the MICHELLE trial of rivaroxaban (Xarelto, Bayer/Janssen) prophylaxis, compared with no preventive oral anticoagulant, in 320 patients who, when hospitalized with COVID-19, had been on parenteral anticoagulants because of an elevated risk for venous thromboembolism. The trial, conducted in Brazil, called for postdischarge rivaroxaban at a once-daily dosage of 10 mg for about 1 month.

The session also includes a presentation called “Insights into the Effects of the COVID-19 Pandemic: Comprehensive Analysis from the GUIDE-HF Trial,” the primary outcomes of which will be reported on the first day of the Congress.

Following is a presentation on the PREPARE-IT study of icosapent ethyl (Vascepa, Amarin), given at high dosages intended to be anti-inflammatory, compared with placebo, in an estimated 4,000 adults. The trial has two groups: A prevention group of adults living and circulating in the community; and a treatment group of patients aged at least 40 years with confirmed symptomatic SARS-CoV-2 infection for whom the need for hospitalization isn’t clear.
 

Monday, Aug. 30

The final day of the Congress features a trial called Influenza Vaccination after Myocardial Infarction (IAMI), which has tested the secondary preventive effect of influenza vaccination by randomly assigning 2,571 patients to receive a standard vaccine or a saline placebo injection on one occasion.

Entry to the international trial called for a diagnosis of MI with or without ST-segment elevation, or stable CAD and age at least 75 years with other risk factors. The patients were followed for death, MI, stent thrombosis, and a slew of secondary endpoints over 12 months.

Monday offerings continue later in a time block leading off with the STEP trial, which has randomly assigned an estimated 8,000 patients at 40 centers in China who are 60 to 80 years of age with a systolic blood pressure of 140 to <190 mm Hg to be on standard guideline-based therapy or an intensive drug-management strategy.

The systolic BP goals are 130 to <150 mm Hg for standard care and 110 to <130 mm Hg for the intensive regimen. The composite primary endpoint includes death and clinical events related to acute coronary syndromes, HF, revascularization, and stroke.

Following on heels of STEP, the Amulet IDE trial – the first major randomized comparison of two transcatheter LAA closure devices – entered 1,878 patients with nonvalvular AFib who were considered high-risk for bleeding and stroke or systemic embolism.

They were randomly assigned in the noninferiority trial to receive either the AMPLATZER Amulet (Abbott Medical Devices) or the WATCHMAN (Boston Scientific) closure devices and were followed for safety and efficacy for up to 5 years.

Both LAA closure devices, intended to make patients with AFib less reliant on oral anticoagulation, are now available on both sides of the Atlantic – as well as many other countries – after the Amulet’s United States market approval on Aug. 16, based largely on the Amulet IDE trial.

Rounding out the final Hot Line set is one of the latest efforts to show the efficacy and safety of a very short DAPT period after coronary stenting in patients with acute coronary syndromes, the STOPDAPT-2 ACS trial.

The study assigned 3,008 patients in Japan to receive aspirin and clopidogrel for either 1 month or 1 year after implantation with an everolimus-eluting cobalt-chromium stent and followed them for up to 5 years for a composite of MI, CV death, stent thrombosis, stroke, and bleeding.

The trial follows the published STOPDAPT-2 trial that showed superiority for the 1-month DAPT regimen in a predominantly stable-CAD population treated with the same kind of stent.
 

Program structure and format

A total of 15 online channels are to be available in the morning, European time, their schedules running in parallel. Presentations often are prerecorded, but also include live sessions at 8:00 a.m. Central time and 12 p.m. CET (2:00 a.m. and 6:00 a.m. Eastern time) to liven up the channel offerings, Dr. Windecker observed, and to make them more immediate and potentially interactive.

Many of the parallel channels are devoted throughout the Congress to particular silos of cardiology; for example, arrhythmias and device therapy is on channel 3; CAD and acute care is on 5; HF is on 6; and preventive cardiology is on 9.

Other channels swing across different topics from day to day, such as channel 1, which covers COVID-19 topics on the first and third day of the meeting, “advances in science” on day 2, and “digital health, public health, health economics” on day 4.

The focus each day, starting at 2:00 p.m. CET (8:00 a.m. ET) and continuing into the evening in Europe, shifts over to the Prime Time live program, which features the Hot Line and guideline presentations and many of the live abstract presentations.

Dr. Kosiborod, not a researcher with the EMPEROR trials, is chair of the Dapagliflozin in Preserved Ejection Fraction Heart Failure ( PRESERVED-HF ) trial, which is scheduled for presentation at the September 2021 Heart Failure Society of American meeting.

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

The United States Preventive Services Task Force has updated its recommendation on the age of screening for prediabetes and type 2 diabetes in the primary care setting – lowering the age from 40 to 35 years for asymptomatic patients who are overweight or obese and encouraging greater interventions when patients do show a risk.

KatarzynaBialasiewicz/Thinkstock

“The USPSTF concludes with moderate certainty that screening for prediabetes and type 2 diabetes and offering or referring patients with prediabetes to effective preventive interventions has a moderate net benefit,” the task force concludes in its recommendation, published Aug. 24 in JAMA.

“Clinicians should offer or refer patients with prediabetes to effective preventive interventions,” they write.

Experts commenting on the issue strongly emphasize that it’s not just the screening, but the subsequent intervention that is needed to make a difference.

“If young adults newly identified with abnormal glucose metabolism do not receive the needed intensive behavioral change support, screening may provide no benefit,” write Richard W. Grant, MD, MPH, and colleagues in an editorial published with the recommendation.

“Given the role of our obesogenic and physically inactive society in the shift toward earlier onset of diabetes, efforts to increase screening and recognition of abnormal glucose metabolism must be coupled with robust public health measures to address the underlying contributors.”
 

BMI cutoff lower for at-risk ethnic populations

The recommendation, which updates the task force’s 2015 guideline, carries a “B” classification, meaning the USPSTF has high certainty that the net benefit is moderate. It now specifies screening from age 35to 70 for persons classified as overweight (body mass index at least 25) or obese (BMI at least 30) and recommends referral to preventive interventions when patients are found to have prediabetes.

In addition to recommendations of lifestyle changes, such as diet and physical activity, the task force also endorses the diabetes drug metformin as a beneficial intervention in the prevention or delay of diabetes, while noting fewer overall health benefits from metformin than from the lifestyle changes.

A lower BMI cutoff of at least 23 is recommended for diabetes screening of Asian Americans, and, importantly, screening for prediabetes and diabetes should be considered at an even earlier age if the patient is from a population with a disproportionately high prevalence of diabetes, including American Indian/Alaska Native, Black, Hawaiian/Pacific Islander, Hispanic/Latino, the task force recommends.

Screening tests should include fasting plasma glucose, hemoglobin A1c, or an oral glucose tolerance test. Although screening every 3 years “may be a reasonable approach for adults with normal blood glucose levels,” the task force adds that “the optimal screening interval for adults with an initial normal glucose test result is uncertain.”
 

Data review: Few with prediabetes know they have it

The need for the update was prompted by troubling data showing increasing diabetes rates despite early signs that can and should be identified and acted upon in the primary care setting to prevent disease progression.

Data from the Centers for Disease Control and Prevention, for instance, show that while 13% of all U.S. adults 18 years or older have diabetes and 35% meet criteria for prediabetes, as many as 21% of those with diabetes were not aware of or did not report having the disease. Furthermore, only a small fraction – 15% of those with prediabetes – said they had been told by a health professional that they had this condition, the task force notes.

The task force’s final recommendation was based on a systematic review of evidence regarding the screening of asymptomatic, nonpregnant adults and the harms and benefits of interventions, such as physical activity, behavioral counseling, or pharmacotherapy.

Among key evidence supporting the lower age was a 2014 study showing that the number of people necessary to obtain one positive test for diabetes with screening sharply drops from 80 among those aged 30-34 years to just 31 among those aged 36-39.

Opportunistic universal screening of eligible people aged 35 and older would yield a ratio of 1 out of just 15 to spot a positive test, the authors of that study reported.

In addition, a large cohort study in more than 77,000 people with prediabetes strongly links the risk of developing diabetes with increases in A1c level and with increasing BMI.
 

ADA recommendations differ

The new recommendations differ from American Diabetes Association guidelines, which call for diabetes screening at all ages for people who are overweight or obese and who have one or more risk factors, such as physical inactivity or a first-degree relative with diabetes. If results are normal, repeat screening at least every 3 years is recommended.

The ADA further recommends universal screening for all adults 45 years and older, regardless of their risk factors.

For the screening of adults over 45, the ADA recommends using a fasting plasma glucose level, 2-hour plasma glucose level during a 75-g oral glucose tolerance test, or A1c level, regardless of risk factors.

The American Association of Clinical Endocrinology also recommends universal screening for prediabetes and diabetes for all adults 45 years or older, regardless of risk factors, and also advises screening those who have risk factors for diabetes regardless of age.
 

Screening of little benefit without behavior change support

In an interview, Dr. Grant added that broad efforts are essential as those at the practice level have clearly not succeeded.

“The medical model of individual counseling and referral has not really been effective, and so we really need to think in terms of large-scale public health action,” said Dr. Grant, of the division of research, Kaiser Permanente Northern California, Oakland.

His editorial details the sweeping, multifactorial efforts that are needed.

“To turn this recommendation into action – that is, to translate screening activities into improved clinical outcomes – change is needed at the patient-clinician level (recognizing and encouraging eligible individuals to be screened), health care system level (reducing screening barriers and ensuring access to robust lifestyle programs), and societal level (applying effective public health interventions to reduce obesity and increase exercise),” they write.

A top priority has to be a focus on individuals of diverse backgrounds and issues such as access to healthy programs in minority communities, Dr. Grant noted.

“Newly diagnosed adults are more likely to be African-American and Latinx,” he said.

“We really need to invest in healthier communities for low-income, non-White communities to reverse the persistent health care disparities in these communities.”

While the challenges may appear daunting, history shows they are not necessarily insurmountable – as evidenced in the campaign to discourage tobacco smoking.

“National smoking cessation efforts are one example of a mostly successful public health campaign that has made a difference in health behaviors,” Grant noted.

The recommendation is also posted on the USPSTF web site .

Dr. Grant reports receiving grants from the National Institutes of Health and the Patient-Centered Outcomes Research Institute.

The United States Preventive Services Task Force has updated its recommendation on the age of screening for prediabetes and type 2 diabetes in the primary care setting – lowering the age from 40 to 35 years for asymptomatic patients who are overweight or obese and encouraging greater interventions when patients do show a risk.

KatarzynaBialasiewicz/Thinkstock

“The USPSTF concludes with moderate certainty that screening for prediabetes and type 2 diabetes and offering or referring patients with prediabetes to effective preventive interventions has a moderate net benefit,” the task force concludes in its recommendation, published Aug. 24 in JAMA.

“Clinicians should offer or refer patients with prediabetes to effective preventive interventions,” they write.

Experts commenting on the issue strongly emphasize that it’s not just the screening, but the subsequent intervention that is needed to make a difference.

“If young adults newly identified with abnormal glucose metabolism do not receive the needed intensive behavioral change support, screening may provide no benefit,” write Richard W. Grant, MD, MPH, and colleagues in an editorial published with the recommendation.

“Given the role of our obesogenic and physically inactive society in the shift toward earlier onset of diabetes, efforts to increase screening and recognition of abnormal glucose metabolism must be coupled with robust public health measures to address the underlying contributors.”
 

BMI cutoff lower for at-risk ethnic populations

The recommendation, which updates the task force’s 2015 guideline, carries a “B” classification, meaning the USPSTF has high certainty that the net benefit is moderate. It now specifies screening from age 35to 70 for persons classified as overweight (body mass index at least 25) or obese (BMI at least 30) and recommends referral to preventive interventions when patients are found to have prediabetes.

In addition to recommendations of lifestyle changes, such as diet and physical activity, the task force also endorses the diabetes drug metformin as a beneficial intervention in the prevention or delay of diabetes, while noting fewer overall health benefits from metformin than from the lifestyle changes.

A lower BMI cutoff of at least 23 is recommended for diabetes screening of Asian Americans, and, importantly, screening for prediabetes and diabetes should be considered at an even earlier age if the patient is from a population with a disproportionately high prevalence of diabetes, including American Indian/Alaska Native, Black, Hawaiian/Pacific Islander, Hispanic/Latino, the task force recommends.

Screening tests should include fasting plasma glucose, hemoglobin A1c, or an oral glucose tolerance test. Although screening every 3 years “may be a reasonable approach for adults with normal blood glucose levels,” the task force adds that “the optimal screening interval for adults with an initial normal glucose test result is uncertain.”
 

Data review: Few with prediabetes know they have it

The need for the update was prompted by troubling data showing increasing diabetes rates despite early signs that can and should be identified and acted upon in the primary care setting to prevent disease progression.

Data from the Centers for Disease Control and Prevention, for instance, show that while 13% of all U.S. adults 18 years or older have diabetes and 35% meet criteria for prediabetes, as many as 21% of those with diabetes were not aware of or did not report having the disease. Furthermore, only a small fraction – 15% of those with prediabetes – said they had been told by a health professional that they had this condition, the task force notes.

The task force’s final recommendation was based on a systematic review of evidence regarding the screening of asymptomatic, nonpregnant adults and the harms and benefits of interventions, such as physical activity, behavioral counseling, or pharmacotherapy.

Among key evidence supporting the lower age was a 2014 study showing that the number of people necessary to obtain one positive test for diabetes with screening sharply drops from 80 among those aged 30-34 years to just 31 among those aged 36-39.

Opportunistic universal screening of eligible people aged 35 and older would yield a ratio of 1 out of just 15 to spot a positive test, the authors of that study reported.

In addition, a large cohort study in more than 77,000 people with prediabetes strongly links the risk of developing diabetes with increases in A1c level and with increasing BMI.
 

ADA recommendations differ

The new recommendations differ from American Diabetes Association guidelines, which call for diabetes screening at all ages for people who are overweight or obese and who have one or more risk factors, such as physical inactivity or a first-degree relative with diabetes. If results are normal, repeat screening at least every 3 years is recommended.

The ADA further recommends universal screening for all adults 45 years and older, regardless of their risk factors.

For the screening of adults over 45, the ADA recommends using a fasting plasma glucose level, 2-hour plasma glucose level during a 75-g oral glucose tolerance test, or A1c level, regardless of risk factors.

The American Association of Clinical Endocrinology also recommends universal screening for prediabetes and diabetes for all adults 45 years or older, regardless of risk factors, and also advises screening those who have risk factors for diabetes regardless of age.
 

Screening of little benefit without behavior change support

In an interview, Dr. Grant added that broad efforts are essential as those at the practice level have clearly not succeeded.

“The medical model of individual counseling and referral has not really been effective, and so we really need to think in terms of large-scale public health action,” said Dr. Grant, of the division of research, Kaiser Permanente Northern California, Oakland.

His editorial details the sweeping, multifactorial efforts that are needed.

“To turn this recommendation into action – that is, to translate screening activities into improved clinical outcomes – change is needed at the patient-clinician level (recognizing and encouraging eligible individuals to be screened), health care system level (reducing screening barriers and ensuring access to robust lifestyle programs), and societal level (applying effective public health interventions to reduce obesity and increase exercise),” they write.

A top priority has to be a focus on individuals of diverse backgrounds and issues such as access to healthy programs in minority communities, Dr. Grant noted.

“Newly diagnosed adults are more likely to be African-American and Latinx,” he said.

“We really need to invest in healthier communities for low-income, non-White communities to reverse the persistent health care disparities in these communities.”

While the challenges may appear daunting, history shows they are not necessarily insurmountable – as evidenced in the campaign to discourage tobacco smoking.

“National smoking cessation efforts are one example of a mostly successful public health campaign that has made a difference in health behaviors,” Grant noted.

The recommendation is also posted on the USPSTF web site .

Dr. Grant reports receiving grants from the National Institutes of Health and the Patient-Centered Outcomes Research Institute.

The United States Preventive Services Task Force has updated its recommendation on the age of screening for prediabetes and type 2 diabetes in the primary care setting – lowering the age from 40 to 35 years for asymptomatic patients who are overweight or obese and encouraging greater interventions when patients do show a risk.

KatarzynaBialasiewicz/Thinkstock

“The USPSTF concludes with moderate certainty that screening for prediabetes and type 2 diabetes and offering or referring patients with prediabetes to effective preventive interventions has a moderate net benefit,” the task force concludes in its recommendation, published Aug. 24 in JAMA.

“Clinicians should offer or refer patients with prediabetes to effective preventive interventions,” they write.

Experts commenting on the issue strongly emphasize that it’s not just the screening, but the subsequent intervention that is needed to make a difference.

“If young adults newly identified with abnormal glucose metabolism do not receive the needed intensive behavioral change support, screening may provide no benefit,” write Richard W. Grant, MD, MPH, and colleagues in an editorial published with the recommendation.

“Given the role of our obesogenic and physically inactive society in the shift toward earlier onset of diabetes, efforts to increase screening and recognition of abnormal glucose metabolism must be coupled with robust public health measures to address the underlying contributors.”
 

BMI cutoff lower for at-risk ethnic populations

The recommendation, which updates the task force’s 2015 guideline, carries a “B” classification, meaning the USPSTF has high certainty that the net benefit is moderate. It now specifies screening from age 35to 70 for persons classified as overweight (body mass index at least 25) or obese (BMI at least 30) and recommends referral to preventive interventions when patients are found to have prediabetes.

In addition to recommendations of lifestyle changes, such as diet and physical activity, the task force also endorses the diabetes drug metformin as a beneficial intervention in the prevention or delay of diabetes, while noting fewer overall health benefits from metformin than from the lifestyle changes.

A lower BMI cutoff of at least 23 is recommended for diabetes screening of Asian Americans, and, importantly, screening for prediabetes and diabetes should be considered at an even earlier age if the patient is from a population with a disproportionately high prevalence of diabetes, including American Indian/Alaska Native, Black, Hawaiian/Pacific Islander, Hispanic/Latino, the task force recommends.

Screening tests should include fasting plasma glucose, hemoglobin A1c, or an oral glucose tolerance test. Although screening every 3 years “may be a reasonable approach for adults with normal blood glucose levels,” the task force adds that “the optimal screening interval for adults with an initial normal glucose test result is uncertain.”
 

Data review: Few with prediabetes know they have it

The need for the update was prompted by troubling data showing increasing diabetes rates despite early signs that can and should be identified and acted upon in the primary care setting to prevent disease progression.

Data from the Centers for Disease Control and Prevention, for instance, show that while 13% of all U.S. adults 18 years or older have diabetes and 35% meet criteria for prediabetes, as many as 21% of those with diabetes were not aware of or did not report having the disease. Furthermore, only a small fraction – 15% of those with prediabetes – said they had been told by a health professional that they had this condition, the task force notes.

The task force’s final recommendation was based on a systematic review of evidence regarding the screening of asymptomatic, nonpregnant adults and the harms and benefits of interventions, such as physical activity, behavioral counseling, or pharmacotherapy.

Among key evidence supporting the lower age was a 2014 study showing that the number of people necessary to obtain one positive test for diabetes with screening sharply drops from 80 among those aged 30-34 years to just 31 among those aged 36-39.

Opportunistic universal screening of eligible people aged 35 and older would yield a ratio of 1 out of just 15 to spot a positive test, the authors of that study reported.

In addition, a large cohort study in more than 77,000 people with prediabetes strongly links the risk of developing diabetes with increases in A1c level and with increasing BMI.
 

ADA recommendations differ

The new recommendations differ from American Diabetes Association guidelines, which call for diabetes screening at all ages for people who are overweight or obese and who have one or more risk factors, such as physical inactivity or a first-degree relative with diabetes. If results are normal, repeat screening at least every 3 years is recommended.

The ADA further recommends universal screening for all adults 45 years and older, regardless of their risk factors.

For the screening of adults over 45, the ADA recommends using a fasting plasma glucose level, 2-hour plasma glucose level during a 75-g oral glucose tolerance test, or A1c level, regardless of risk factors.

The American Association of Clinical Endocrinology also recommends universal screening for prediabetes and diabetes for all adults 45 years or older, regardless of risk factors, and also advises screening those who have risk factors for diabetes regardless of age.
 

Screening of little benefit without behavior change support

In an interview, Dr. Grant added that broad efforts are essential as those at the practice level have clearly not succeeded.

“The medical model of individual counseling and referral has not really been effective, and so we really need to think in terms of large-scale public health action,” said Dr. Grant, of the division of research, Kaiser Permanente Northern California, Oakland.

His editorial details the sweeping, multifactorial efforts that are needed.

“To turn this recommendation into action – that is, to translate screening activities into improved clinical outcomes – change is needed at the patient-clinician level (recognizing and encouraging eligible individuals to be screened), health care system level (reducing screening barriers and ensuring access to robust lifestyle programs), and societal level (applying effective public health interventions to reduce obesity and increase exercise),” they write.

A top priority has to be a focus on individuals of diverse backgrounds and issues such as access to healthy programs in minority communities, Dr. Grant noted.

“Newly diagnosed adults are more likely to be African-American and Latinx,” he said.

“We really need to invest in healthier communities for low-income, non-White communities to reverse the persistent health care disparities in these communities.”

While the challenges may appear daunting, history shows they are not necessarily insurmountable – as evidenced in the campaign to discourage tobacco smoking.

“National smoking cessation efforts are one example of a mostly successful public health campaign that has made a difference in health behaviors,” Grant noted.

The recommendation is also posted on the USPSTF web site .

Dr. Grant reports receiving grants from the National Institutes of Health and the Patient-Centered Outcomes Research Institute.

U.S. prescribing data from 160,000 adults with type 2 diabetes and diabetic kidney disease showed a notable uptick in new prescriptions for sodium-glucose cotransporter 2 inhibitors and less dramatic gains for glucagonlike peptide–1 receptor agonists during 2019 and continuing into early 2020, compared with prior years, with usage levels of both classes during the first quarter of 2020 rivaling those of more traditional agents including metformin and insulin.

During the first 3 months of 2020, initiation of a SGLT2 inhibitor constituted 13% of all new starts of an antidiabetes drug among adults with type 2 diabetes and diabetic kidney disease (DKD). This compared with initiation rates during the same early 2020 period of 17% for GLP-1 receptor agonists, 19% for metformin, 16% for sulfonylureas, 15% for insulins, 14% for thiazolidinediones, and 6% for dipeptidyl peptidase–4 inhibitors, the seven drug classes examined in a study published in Diabetes Care.

Early 2020 was the first time that starts of a GLP-1 receptor agonist ranked second (behind only metformin) among these seven drug classes in the studied U.S. population, and early 2020 also marked an unprecedentedly high start rate for SGLT2 inhibitors that nearly tripled the roughly 5% rate in place as recently as 2018.
 

Rises are ‘what we expected’

The recent rise of SGLT2 inhibitors and GLP-1 receptor agonists in these patients “was what we expected,” given the evidence for both classes in slowing progression of DKD, said Julie M. Paik, MD, senior author on the study and a nephrologist and pharmacoepidemiologist at Brigham and Women’s Hospital in Boston.

“We’ve seen other beneficial drugs slow on the uptake, so it’s not surprising to see it here, and I’m optimistic” about further increases going forward, she said in an interview.

Both drug classes “were originally marketed as diabetes drugs,” and it is only since 2019, with the publication of trials showing dramatic renal benefits from canagliflozin (Invokana) in CREDENCE, and from dapagliflozin (Farxiga) in DAPA-CKD in 2020 that the evidence became truly compelling for SGLT2 inhibitors. This evidence also led to new renal-protection indications approved by the Food and Drug Administration for canagliflozin and for dapagliflozin, noted Dr. Paik.

Evidence for renal protection also emerged in 2017 for the GLP-1 receptor agonist liraglutide (Victoza) in the LEADER trial, and for dulaglutide (Trulicity) in the AWARD-7 trial, although neither drug has received a renal indication in its labeling.

By 2020, guidelines for managing patients with type 2 diabetes and chronic kidney disease from the influential Kidney Disease: Improving Global Outcomes organization had identified agents from the SGLT2 inhibitor class as top-tier options, along with metformin, for treating these patients, with agents from the GLP-1 receptor agonist class as the top third class to add in patients who require additional glycemic control.

Additional analyses Dr. Paik and associates ran showed how this played out in terms of which specialists prescribed these drugs during the full period studied beginning in 2013. Throughout this roughly 7-year span, about 70% of the prescriptions written for either SGLT2 inhibitors or for GLP-1 receptor agonists were from internal medicine physicians, followed by about 20% written by endocrinologists. Prescriptions from nephrologists, as well as from cardiologists, have hovered at about 5% each, but seem poised to start rising based on the recently added indications and newer treatment recommendations.

“It’s good to see the recent uptick in use since 2019,” Katherine R. Tuttle, MD, commented in an interview. It’s a positive development for U.S. public health, “but we need to do more to disseminate and implement these life-, kidney-, and heart-saving therapies.”

Future use could approach 80% of DKD patients

Dr. Tuttle estimated that “target” levels of use for SGLT2 inhibitors and for GLP-1 receptor agonists “could reasonably approach 80%” for patients with type 2 diabetes and diabetic kidney disease.

“We will likely move to combination therapy” with simultaneous use of agents from both classes in a targeted way using “precision phenotyping based on clinical characteristics, and eventually perhaps by biomarkers, kidney biopsies, or both.” Combined treatment with both an SGLT2 inhibitor and a GLP-1 receptor agonist may be especially suited to patients with type 2 diabetes, atherosclerotic cardiovascular disease, low estimated glomerular filtration rate, and need for better glycemic control and weight loss, a profile that is “pretty typical” in real-world practice, said Dr. Tuttle, a nephrologist and endocrinologist and executive director for research at Providence Healthcare in Spokane, Wash.
 

Study included patients with commercial or Medicare Advantage coverage

The study used information in an Optum database that included patients enrolled in either commercial or in Medicare Advantage health insurance plans from 2013 to the first quarter of 2020. This included 160,489 adults with type 2 diabetes and DKD who started during that period at least one agent from any of the seven included drug classes.

This focus may have biased the findings because, overall, U.S. coverage of the relatively expensive agents from the SGLT2 inhibitor and GLP-1 receptor agonist classes has often been problematic.

“There are issues of cost, coverage, and access” using these medications, as well as limited data on cost-effectiveness, Dr. Paik acknowledged. Additional issues that have helped generate prescribing lags include concerns about possible adverse effects, low familiarity by providers with these drugs early on, and limited trial experience using them in older patients. The process of clinicians growing more comfortable prescribing these new agents has depended on their “working through the evidence,” she explained.

The FDA’s approval in July 2021 of finerenone (Kerendia) for treating patients with type 2 diabetes and chronic kidney disease threw yet another new variable into the prescribing mix for these patients.

“SGLT2 inhibitors are here to stay as a new standard of care for patients with diabetic kidney disease, but combination with finerenone might be especially useful for patients with diabetic kidney disease and heart failure,” Dr. Tuttle suggested. A new generation of clinical trials will likely soon launch to test these combinations, she predicted.

Dr. Paik had no disclosures. Dr. Tuttle has been a consultant to AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, Goldfinch Bio, Eli Lilly, and Novo Nordisk.

[email protected]

U.S. prescribing data from 160,000 adults with type 2 diabetes and diabetic kidney disease showed a notable uptick in new prescriptions for sodium-glucose cotransporter 2 inhibitors and less dramatic gains for glucagonlike peptide–1 receptor agonists during 2019 and continuing into early 2020, compared with prior years, with usage levels of both classes during the first quarter of 2020 rivaling those of more traditional agents including metformin and insulin.

During the first 3 months of 2020, initiation of a SGLT2 inhibitor constituted 13% of all new starts of an antidiabetes drug among adults with type 2 diabetes and diabetic kidney disease (DKD). This compared with initiation rates during the same early 2020 period of 17% for GLP-1 receptor agonists, 19% for metformin, 16% for sulfonylureas, 15% for insulins, 14% for thiazolidinediones, and 6% for dipeptidyl peptidase–4 inhibitors, the seven drug classes examined in a study published in Diabetes Care.

Early 2020 was the first time that starts of a GLP-1 receptor agonist ranked second (behind only metformin) among these seven drug classes in the studied U.S. population, and early 2020 also marked an unprecedentedly high start rate for SGLT2 inhibitors that nearly tripled the roughly 5% rate in place as recently as 2018.
 

Rises are ‘what we expected’

The recent rise of SGLT2 inhibitors and GLP-1 receptor agonists in these patients “was what we expected,” given the evidence for both classes in slowing progression of DKD, said Julie M. Paik, MD, senior author on the study and a nephrologist and pharmacoepidemiologist at Brigham and Women’s Hospital in Boston.

“We’ve seen other beneficial drugs slow on the uptake, so it’s not surprising to see it here, and I’m optimistic” about further increases going forward, she said in an interview.

Both drug classes “were originally marketed as diabetes drugs,” and it is only since 2019, with the publication of trials showing dramatic renal benefits from canagliflozin (Invokana) in CREDENCE, and from dapagliflozin (Farxiga) in DAPA-CKD in 2020 that the evidence became truly compelling for SGLT2 inhibitors. This evidence also led to new renal-protection indications approved by the Food and Drug Administration for canagliflozin and for dapagliflozin, noted Dr. Paik.

Evidence for renal protection also emerged in 2017 for the GLP-1 receptor agonist liraglutide (Victoza) in the LEADER trial, and for dulaglutide (Trulicity) in the AWARD-7 trial, although neither drug has received a renal indication in its labeling.

By 2020, guidelines for managing patients with type 2 diabetes and chronic kidney disease from the influential Kidney Disease: Improving Global Outcomes organization had identified agents from the SGLT2 inhibitor class as top-tier options, along with metformin, for treating these patients, with agents from the GLP-1 receptor agonist class as the top third class to add in patients who require additional glycemic control.

Additional analyses Dr. Paik and associates ran showed how this played out in terms of which specialists prescribed these drugs during the full period studied beginning in 2013. Throughout this roughly 7-year span, about 70% of the prescriptions written for either SGLT2 inhibitors or for GLP-1 receptor agonists were from internal medicine physicians, followed by about 20% written by endocrinologists. Prescriptions from nephrologists, as well as from cardiologists, have hovered at about 5% each, but seem poised to start rising based on the recently added indications and newer treatment recommendations.

“It’s good to see the recent uptick in use since 2019,” Katherine R. Tuttle, MD, commented in an interview. It’s a positive development for U.S. public health, “but we need to do more to disseminate and implement these life-, kidney-, and heart-saving therapies.”

Future use could approach 80% of DKD patients

Dr. Tuttle estimated that “target” levels of use for SGLT2 inhibitors and for GLP-1 receptor agonists “could reasonably approach 80%” for patients with type 2 diabetes and diabetic kidney disease.

“We will likely move to combination therapy” with simultaneous use of agents from both classes in a targeted way using “precision phenotyping based on clinical characteristics, and eventually perhaps by biomarkers, kidney biopsies, or both.” Combined treatment with both an SGLT2 inhibitor and a GLP-1 receptor agonist may be especially suited to patients with type 2 diabetes, atherosclerotic cardiovascular disease, low estimated glomerular filtration rate, and need for better glycemic control and weight loss, a profile that is “pretty typical” in real-world practice, said Dr. Tuttle, a nephrologist and endocrinologist and executive director for research at Providence Healthcare in Spokane, Wash.
 

Study included patients with commercial or Medicare Advantage coverage

The study used information in an Optum database that included patients enrolled in either commercial or in Medicare Advantage health insurance plans from 2013 to the first quarter of 2020. This included 160,489 adults with type 2 diabetes and DKD who started during that period at least one agent from any of the seven included drug classes.

This focus may have biased the findings because, overall, U.S. coverage of the relatively expensive agents from the SGLT2 inhibitor and GLP-1 receptor agonist classes has often been problematic.

“There are issues of cost, coverage, and access” using these medications, as well as limited data on cost-effectiveness, Dr. Paik acknowledged. Additional issues that have helped generate prescribing lags include concerns about possible adverse effects, low familiarity by providers with these drugs early on, and limited trial experience using them in older patients. The process of clinicians growing more comfortable prescribing these new agents has depended on their “working through the evidence,” she explained.

The FDA’s approval in July 2021 of finerenone (Kerendia) for treating patients with type 2 diabetes and chronic kidney disease threw yet another new variable into the prescribing mix for these patients.

“SGLT2 inhibitors are here to stay as a new standard of care for patients with diabetic kidney disease, but combination with finerenone might be especially useful for patients with diabetic kidney disease and heart failure,” Dr. Tuttle suggested. A new generation of clinical trials will likely soon launch to test these combinations, she predicted.

Dr. Paik had no disclosures. Dr. Tuttle has been a consultant to AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, Goldfinch Bio, Eli Lilly, and Novo Nordisk.

[email protected]

U.S. prescribing data from 160,000 adults with type 2 diabetes and diabetic kidney disease showed a notable uptick in new prescriptions for sodium-glucose cotransporter 2 inhibitors and less dramatic gains for glucagonlike peptide–1 receptor agonists during 2019 and continuing into early 2020, compared with prior years, with usage levels of both classes during the first quarter of 2020 rivaling those of more traditional agents including metformin and insulin.

During the first 3 months of 2020, initiation of a SGLT2 inhibitor constituted 13% of all new starts of an antidiabetes drug among adults with type 2 diabetes and diabetic kidney disease (DKD). This compared with initiation rates during the same early 2020 period of 17% for GLP-1 receptor agonists, 19% for metformin, 16% for sulfonylureas, 15% for insulins, 14% for thiazolidinediones, and 6% for dipeptidyl peptidase–4 inhibitors, the seven drug classes examined in a study published in Diabetes Care.

Early 2020 was the first time that starts of a GLP-1 receptor agonist ranked second (behind only metformin) among these seven drug classes in the studied U.S. population, and early 2020 also marked an unprecedentedly high start rate for SGLT2 inhibitors that nearly tripled the roughly 5% rate in place as recently as 2018.
 

Rises are ‘what we expected’

The recent rise of SGLT2 inhibitors and GLP-1 receptor agonists in these patients “was what we expected,” given the evidence for both classes in slowing progression of DKD, said Julie M. Paik, MD, senior author on the study and a nephrologist and pharmacoepidemiologist at Brigham and Women’s Hospital in Boston.

“We’ve seen other beneficial drugs slow on the uptake, so it’s not surprising to see it here, and I’m optimistic” about further increases going forward, she said in an interview.

Both drug classes “were originally marketed as diabetes drugs,” and it is only since 2019, with the publication of trials showing dramatic renal benefits from canagliflozin (Invokana) in CREDENCE, and from dapagliflozin (Farxiga) in DAPA-CKD in 2020 that the evidence became truly compelling for SGLT2 inhibitors. This evidence also led to new renal-protection indications approved by the Food and Drug Administration for canagliflozin and for dapagliflozin, noted Dr. Paik.

Evidence for renal protection also emerged in 2017 for the GLP-1 receptor agonist liraglutide (Victoza) in the LEADER trial, and for dulaglutide (Trulicity) in the AWARD-7 trial, although neither drug has received a renal indication in its labeling.

By 2020, guidelines for managing patients with type 2 diabetes and chronic kidney disease from the influential Kidney Disease: Improving Global Outcomes organization had identified agents from the SGLT2 inhibitor class as top-tier options, along with metformin, for treating these patients, with agents from the GLP-1 receptor agonist class as the top third class to add in patients who require additional glycemic control.

Additional analyses Dr. Paik and associates ran showed how this played out in terms of which specialists prescribed these drugs during the full period studied beginning in 2013. Throughout this roughly 7-year span, about 70% of the prescriptions written for either SGLT2 inhibitors or for GLP-1 receptor agonists were from internal medicine physicians, followed by about 20% written by endocrinologists. Prescriptions from nephrologists, as well as from cardiologists, have hovered at about 5% each, but seem poised to start rising based on the recently added indications and newer treatment recommendations.

“It’s good to see the recent uptick in use since 2019,” Katherine R. Tuttle, MD, commented in an interview. It’s a positive development for U.S. public health, “but we need to do more to disseminate and implement these life-, kidney-, and heart-saving therapies.”

Future use could approach 80% of DKD patients

Dr. Tuttle estimated that “target” levels of use for SGLT2 inhibitors and for GLP-1 receptor agonists “could reasonably approach 80%” for patients with type 2 diabetes and diabetic kidney disease.

“We will likely move to combination therapy” with simultaneous use of agents from both classes in a targeted way using “precision phenotyping based on clinical characteristics, and eventually perhaps by biomarkers, kidney biopsies, or both.” Combined treatment with both an SGLT2 inhibitor and a GLP-1 receptor agonist may be especially suited to patients with type 2 diabetes, atherosclerotic cardiovascular disease, low estimated glomerular filtration rate, and need for better glycemic control and weight loss, a profile that is “pretty typical” in real-world practice, said Dr. Tuttle, a nephrologist and endocrinologist and executive director for research at Providence Healthcare in Spokane, Wash.
 

Study included patients with commercial or Medicare Advantage coverage

The study used information in an Optum database that included patients enrolled in either commercial or in Medicare Advantage health insurance plans from 2013 to the first quarter of 2020. This included 160,489 adults with type 2 diabetes and DKD who started during that period at least one agent from any of the seven included drug classes.

This focus may have biased the findings because, overall, U.S. coverage of the relatively expensive agents from the SGLT2 inhibitor and GLP-1 receptor agonist classes has often been problematic.

“There are issues of cost, coverage, and access” using these medications, as well as limited data on cost-effectiveness, Dr. Paik acknowledged. Additional issues that have helped generate prescribing lags include concerns about possible adverse effects, low familiarity by providers with these drugs early on, and limited trial experience using them in older patients. The process of clinicians growing more comfortable prescribing these new agents has depended on their “working through the evidence,” she explained.

The FDA’s approval in July 2021 of finerenone (Kerendia) for treating patients with type 2 diabetes and chronic kidney disease threw yet another new variable into the prescribing mix for these patients.

“SGLT2 inhibitors are here to stay as a new standard of care for patients with diabetic kidney disease, but combination with finerenone might be especially useful for patients with diabetic kidney disease and heart failure,” Dr. Tuttle suggested. A new generation of clinical trials will likely soon launch to test these combinations, she predicted.

Dr. Paik had no disclosures. Dr. Tuttle has been a consultant to AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, Goldfinch Bio, Eli Lilly, and Novo Nordisk.

[email protected]

For patients with coronary heart disease (CHD), following a Mediterranean diet is more effective in reducing progression of atherosclerosis than following a low-fat diet, according to new data from the CORDIOPREV randomized, controlled trial.

OksanaKiian/Getty Images

“The current study is, to our knowledge, the first to establish an effective dietary strategy for secondary cardiovascular prevention, reinforcing the fact that the Mediterranean diet rich in extra virgin olive oil (EVOO) could prevent the progression of atherosclerosis,” the study team said.

The data also show that patients with a higher atherosclerotic burden might benefit the most from the Mediterranean diet.

The study was published online Aug. 10, 2021, in Stroke.
 

Mediterranean or low fat?

“It is well established that lifestyle and dietary habits powerfully affect cardiovascular risk,” study investigator Elena M. Yubero-Serrano, PhD, with Reina Sofia University Hospital/University of Cordoba (Spain), told this news organization.

“The effectiveness of the Mediterranean diet in reducing cardiovascular risk has been seen in primary prevention. However, currently there is no consensus about a recommended dietary model for the secondary prevention of cardiovascular disease,” she said.

The Coronary Diet Intervention With Olive Oil and Cardiovascular Prevention (CORDIOPREV) study is an ongoing prospective study comparing the effects of two healthy diets for secondary prevention of cardiovascular disease (CVD) in 1002 patients.

The comparative effect of the diets in reducing CVD risk, assessed by quantification of intima-media thickness of the common carotid arteries (IMT-CC), is a key secondary endpoint of the study.

During the study, half of the patients follow a Mediterranean diet rich in EVOO, fruit and vegetables, whole grains, fish, and nuts. The other half follow a diet low in fat and rich in complex carbohydrates.

A total of 939 participants (459 in the low-fat diet group and 480 in the Mediterranean diet group) completed IMT-CC evaluation at baseline, and 809 (377 and 432, respectively) completed the IMT-CC evaluation at 5 years; 731 (335 and 396, respectively) did so at 7 years.

The Mediterranean diet significantly decreased IMT-CC both after 5 years (–0.027; P < .001) and after 7 years (–0.031 mm; P < .001), relative to baseline. In contrast, the low-fat diet did not exert any change on IMT-CC after 5 or 7 years, the researchers report.

The higher the IMT-CC at baseline, the greater the reduction in this parameter.

The Mediterranean diet also produced a greater decrease in IMT-CC and carotid plaque maximum height, compared with the low-fat diet throughout follow-up.

There were no between-group differences in carotid plaque numbers during follow-up.

“Our findings, in addition to reinforcing the clinical benefits of the Mediterranean diet, provide a beneficial dietary strategy as a clinical and therapeutic tool that could reduce the high cardiovascular recurrence in the context of secondary prevention,” Dr. Yubero-Serrano said in an interview.

Earlier data from CORDIOPREV showed that, after 1 year of eating a Mediterranean diet, compared with the low-fat diet, endothelial function was improved among patients with CHD, even those with type 2 diabetes, which was associated with a better balance of vascular homeostasis.

The Mediterranean diet may also modulate the lipid profile, particularly by increasing HDL cholesterol levels. The anti-inflammatory capacity of the Mediterranean diet could be another factor that contributes to reducing the progression of atherosclerosis, the researchers say.
 

Important study

Reached for comment, Alan Rozanski, MD, professor of medicine, Icahn School of Medicine at Mount Sinai and cardiologist at Mount Sinai Morningside, New York, said: “We know very well that lifestyle factors, diet, and exercise in particular are extremely important in promoting health, vitality, and decreasing risk for chronic diseases, including heart attack and stroke.

“But a lot of the studies depend on epidemiological work. Until now, we haven’t had important prospective studies evaluating different kinds of dietary approaches and how they affect carotid intimal thickening assessments that we can do by ultrasound. So having this kind of imaging study which shows that diet can halt progression of atherosclerosis is important,” said Dr. Rozanski.

“Changing one’s diet is extremely important and potentially beneficial in many ways, and being able to say to a patient with atherosclerosis that we have data that shows you can halt the progression of the disease can be extraordinarily encouraging to many patients,” he noted.

“When people have disease, they very often gravitate toward drugs, but continuing to emphasize lifestyle changes in these people is extremely important,” he added.

The CORDIOPREV study was supported by the Fundación Patrimonio Comunal Olivarero. Dr. Yubero-Serrano and Dr. Rozanski disclosed no relevant financial relationships.

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

For patients with coronary heart disease (CHD), following a Mediterranean diet is more effective in reducing progression of atherosclerosis than following a low-fat diet, according to new data from the CORDIOPREV randomized, controlled trial.

OksanaKiian/Getty Images

“The current study is, to our knowledge, the first to establish an effective dietary strategy for secondary cardiovascular prevention, reinforcing the fact that the Mediterranean diet rich in extra virgin olive oil (EVOO) could prevent the progression of atherosclerosis,” the study team said.

The data also show that patients with a higher atherosclerotic burden might benefit the most from the Mediterranean diet.

The study was published online Aug. 10, 2021, in Stroke.
 

Mediterranean or low fat?

“It is well established that lifestyle and dietary habits powerfully affect cardiovascular risk,” study investigator Elena M. Yubero-Serrano, PhD, with Reina Sofia University Hospital/University of Cordoba (Spain), told this news organization.

“The effectiveness of the Mediterranean diet in reducing cardiovascular risk has been seen in primary prevention. However, currently there is no consensus about a recommended dietary model for the secondary prevention of cardiovascular disease,” she said.

The Coronary Diet Intervention With Olive Oil and Cardiovascular Prevention (CORDIOPREV) study is an ongoing prospective study comparing the effects of two healthy diets for secondary prevention of cardiovascular disease (CVD) in 1002 patients.

The comparative effect of the diets in reducing CVD risk, assessed by quantification of intima-media thickness of the common carotid arteries (IMT-CC), is a key secondary endpoint of the study.

During the study, half of the patients follow a Mediterranean diet rich in EVOO, fruit and vegetables, whole grains, fish, and nuts. The other half follow a diet low in fat and rich in complex carbohydrates.

A total of 939 participants (459 in the low-fat diet group and 480 in the Mediterranean diet group) completed IMT-CC evaluation at baseline, and 809 (377 and 432, respectively) completed the IMT-CC evaluation at 5 years; 731 (335 and 396, respectively) did so at 7 years.

The Mediterranean diet significantly decreased IMT-CC both after 5 years (–0.027; P < .001) and after 7 years (–0.031 mm; P < .001), relative to baseline. In contrast, the low-fat diet did not exert any change on IMT-CC after 5 or 7 years, the researchers report.

The higher the IMT-CC at baseline, the greater the reduction in this parameter.

The Mediterranean diet also produced a greater decrease in IMT-CC and carotid plaque maximum height, compared with the low-fat diet throughout follow-up.

There were no between-group differences in carotid plaque numbers during follow-up.

“Our findings, in addition to reinforcing the clinical benefits of the Mediterranean diet, provide a beneficial dietary strategy as a clinical and therapeutic tool that could reduce the high cardiovascular recurrence in the context of secondary prevention,” Dr. Yubero-Serrano said in an interview.

Earlier data from CORDIOPREV showed that, after 1 year of eating a Mediterranean diet, compared with the low-fat diet, endothelial function was improved among patients with CHD, even those with type 2 diabetes, which was associated with a better balance of vascular homeostasis.

The Mediterranean diet may also modulate the lipid profile, particularly by increasing HDL cholesterol levels. The anti-inflammatory capacity of the Mediterranean diet could be another factor that contributes to reducing the progression of atherosclerosis, the researchers say.
 

Important study

Reached for comment, Alan Rozanski, MD, professor of medicine, Icahn School of Medicine at Mount Sinai and cardiologist at Mount Sinai Morningside, New York, said: “We know very well that lifestyle factors, diet, and exercise in particular are extremely important in promoting health, vitality, and decreasing risk for chronic diseases, including heart attack and stroke.

“But a lot of the studies depend on epidemiological work. Until now, we haven’t had important prospective studies evaluating different kinds of dietary approaches and how they affect carotid intimal thickening assessments that we can do by ultrasound. So having this kind of imaging study which shows that diet can halt progression of atherosclerosis is important,” said Dr. Rozanski.

“Changing one’s diet is extremely important and potentially beneficial in many ways, and being able to say to a patient with atherosclerosis that we have data that shows you can halt the progression of the disease can be extraordinarily encouraging to many patients,” he noted.

“When people have disease, they very often gravitate toward drugs, but continuing to emphasize lifestyle changes in these people is extremely important,” he added.

The CORDIOPREV study was supported by the Fundación Patrimonio Comunal Olivarero. Dr. Yubero-Serrano and Dr. Rozanski disclosed no relevant financial relationships.

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

For patients with coronary heart disease (CHD), following a Mediterranean diet is more effective in reducing progression of atherosclerosis than following a low-fat diet, according to new data from the CORDIOPREV randomized, controlled trial.

OksanaKiian/Getty Images

“The current study is, to our knowledge, the first to establish an effective dietary strategy for secondary cardiovascular prevention, reinforcing the fact that the Mediterranean diet rich in extra virgin olive oil (EVOO) could prevent the progression of atherosclerosis,” the study team said.

The data also show that patients with a higher atherosclerotic burden might benefit the most from the Mediterranean diet.

The study was published online Aug. 10, 2021, in Stroke.
 

Mediterranean or low fat?

“It is well established that lifestyle and dietary habits powerfully affect cardiovascular risk,” study investigator Elena M. Yubero-Serrano, PhD, with Reina Sofia University Hospital/University of Cordoba (Spain), told this news organization.

“The effectiveness of the Mediterranean diet in reducing cardiovascular risk has been seen in primary prevention. However, currently there is no consensus about a recommended dietary model for the secondary prevention of cardiovascular disease,” she said.

The Coronary Diet Intervention With Olive Oil and Cardiovascular Prevention (CORDIOPREV) study is an ongoing prospective study comparing the effects of two healthy diets for secondary prevention of cardiovascular disease (CVD) in 1002 patients.

The comparative effect of the diets in reducing CVD risk, assessed by quantification of intima-media thickness of the common carotid arteries (IMT-CC), is a key secondary endpoint of the study.

During the study, half of the patients follow a Mediterranean diet rich in EVOO, fruit and vegetables, whole grains, fish, and nuts. The other half follow a diet low in fat and rich in complex carbohydrates.

A total of 939 participants (459 in the low-fat diet group and 480 in the Mediterranean diet group) completed IMT-CC evaluation at baseline, and 809 (377 and 432, respectively) completed the IMT-CC evaluation at 5 years; 731 (335 and 396, respectively) did so at 7 years.

The Mediterranean diet significantly decreased IMT-CC both after 5 years (–0.027; P < .001) and after 7 years (–0.031 mm; P < .001), relative to baseline. In contrast, the low-fat diet did not exert any change on IMT-CC after 5 or 7 years, the researchers report.

The higher the IMT-CC at baseline, the greater the reduction in this parameter.

The Mediterranean diet also produced a greater decrease in IMT-CC and carotid plaque maximum height, compared with the low-fat diet throughout follow-up.

There were no between-group differences in carotid plaque numbers during follow-up.

“Our findings, in addition to reinforcing the clinical benefits of the Mediterranean diet, provide a beneficial dietary strategy as a clinical and therapeutic tool that could reduce the high cardiovascular recurrence in the context of secondary prevention,” Dr. Yubero-Serrano said in an interview.

Earlier data from CORDIOPREV showed that, after 1 year of eating a Mediterranean diet, compared with the low-fat diet, endothelial function was improved among patients with CHD, even those with type 2 diabetes, which was associated with a better balance of vascular homeostasis.

The Mediterranean diet may also modulate the lipid profile, particularly by increasing HDL cholesterol levels. The anti-inflammatory capacity of the Mediterranean diet could be another factor that contributes to reducing the progression of atherosclerosis, the researchers say.
 

Important study

Reached for comment, Alan Rozanski, MD, professor of medicine, Icahn School of Medicine at Mount Sinai and cardiologist at Mount Sinai Morningside, New York, said: “We know very well that lifestyle factors, diet, and exercise in particular are extremely important in promoting health, vitality, and decreasing risk for chronic diseases, including heart attack and stroke.

“But a lot of the studies depend on epidemiological work. Until now, we haven’t had important prospective studies evaluating different kinds of dietary approaches and how they affect carotid intimal thickening assessments that we can do by ultrasound. So having this kind of imaging study which shows that diet can halt progression of atherosclerosis is important,” said Dr. Rozanski.

“Changing one’s diet is extremely important and potentially beneficial in many ways, and being able to say to a patient with atherosclerosis that we have data that shows you can halt the progression of the disease can be extraordinarily encouraging to many patients,” he noted.

“When people have disease, they very often gravitate toward drugs, but continuing to emphasize lifestyle changes in these people is extremely important,” he added.

The CORDIOPREV study was supported by the Fundación Patrimonio Comunal Olivarero. Dr. Yubero-Serrano and Dr. Rozanski disclosed no relevant financial relationships.

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