Heart Failure

A low-sodium diet was not associated with a reduction in future clinical events in a new study in ambulatory patients with heart failure. But there was a moderate benefit on quality of life and New York Heart Association (NYHA) functional class.

“The guidelines used to strongly recommend a reduction in sodium intake in heart failure patients, but this advice has backed off in recent years because of the lack of data. Most heart failure guidelines now do not make any recommendations on dietary sodium,” he said.

SODIUM-HF was a pragmatic, multinational, open-label, randomized trial conducted in six countries (Australia, Canada, Chile, Colombia, Mexico, and New Zealand), which included 809 patients (median age, 67 years) with chronic heart failure (NYHA functional class II–III) who were receiving optimally tolerated guideline-directed medical treatment. They were randomly assigned to usual care according to local guidelines or a low-sodium diet of less than 100 mmol (<1,500 mg/day). Patients with a baseline sodium intake of less than 1,500 mg/day were excluded.

In the intervention group, patients were asked to follow low-sodium menus developed by dietitians localized to each region. They also received behavioral counseling by trained dietitians or physicians or nurses.

Dietary sodium intake was assessed by using a 3-day food record (including 1 weekend day) at baseline, 6 months, and 12 months in both groups and, for the intervention group, also at 3 and 9 months to monitor and support dietary adherence.

Dr. Ezekowitz explained that although the best method for measuring sodium levels would normally be a 24-hour urine sodium, this would be impractical in a large clinical trial. In addition, he pointed out that urinary sodium is not an accurate measure of actual sodium levels in patients taking diuretics, so it is not a good measure to use in a heart failure population.

“The food record method of assessing sodium levels has been well validated; I think we measured it as accurately as we could have done,” he added.

Results showed that between baseline and 12 months, the median sodium intake decreased from 2,286 mg/day to 1,658 mg/day in the low-sodium group and from 2,119 mg/day to 2,073 mg/day in the usual care group. The median difference between groups was 415 mg/day at 12 months.

By 12 months, events comprising the primary outcome (hospitalization or emergency department visits due to cardiovascular causes or all-cause death) had occurred in 15% of patients in the low-sodium diet group and 17% of those in the usual care group (hazard ratio [HR], 0.89 [95% CI, 0.63 - 1.26]; P = .53).

All-cause death occurred in 6% of patients in the low-sodium diet group and 4% of those in the usual care group (HR, 1.38; P = .32). Cardiovascular-related hospitalization occurred in 10% of the low-sodium group and 12% of the usual care group (HR, 0.82; P = .36), and cardiovascular-related emergency department visits occurred in 4% of both groups (HR, 1.21; P = .60).

The absence of treatment effect for the primary outcome was consistent across most prespecified subgroups, including those with higher vs lower baseline sodium intake. But there was a suggestion of a greater reduction in the primary outcome in individuals younger than age 65 years than in those age 65 years and older.

Quality-of-life measures on the Kansas City Cardiomyopathy Questionnaire (KCCQ) suggested a benefit in the low-sodium group, with mean between-group differences in the change from baseline to 12 months of 3.38 points in the overall summary score, 3.29 points in the clinical summary score, and 3.77 points in the physical limitation score (all differences were statistically significant).

There was no significant difference in 6-minute-walk distance at 12 months between the low-sodium diet group and the usual care group.

NYHA functional class at 12 months differed significantly between groups; the low-sodium diet group had a greater likelihood of improving by one NYHA class than the usual care group (odds ratio, 0.59; P = .0061).

No safety events related to the study treatment were reported in either group.

Dr. Ezekowitz said that to investigate whether longer follow-up may show a difference in events, further analyses are planned at 2 years and 5 years.

Questions on food recall and blinding

Commenting on the findings at the late-breaking clinical trials session at the ACC meeting, Biykem Bozkurt, MD, professor of medicine at Baylor College of Medicine, Houston, congratulated Dr. Ezekowitz on conducting this trial.

“We have been chasing the holy grail of sodium reduction in heart failure for a very long time, so I have to commend you and your team for taking on this challenge, especially during the pandemic,” she said.

But Dr. Bozkurt questioned whether the intervention group actually had a meaningful sodium reduction given that this was measured by food recall and this may have been accounted for by under-reporting of certain food intakes.

Dr. Ezekowitz responded that patients acted as their own controls in that calorie intake, fluid intake, and weight were also assessed and did not change. “So I think we did have a meaningful reduction in sodium,” he said.

Dr. Bozkurt also queried whether the improvements in quality of life and functional status were reliable given that this was an unblinded study.

To this point, Dr. Ezekowitz pointed out that the KCCQ quality-of-life measure was a highly validated instrument and that improvements were seen in these measures at 3, 6, and 12 months. “It is not like these were spurious findings, so I think we have to look at this as a real result,” he argued.

Commenting on the study at an ACC press conference, Mary Norine Walsh, MD, director of the heart failure and cardiac transplantation programs at St. Vincent Heart Center in Indianapolis, said the trial had answered two important questions: that sodium reduction in heart failure may not reduce heart failure hospitalization/death but that patients feel better.

“I think we can safely tell patients that if they slip up a bit they may not end up in hospital,” she added.

This study was funded by the Canadian Institutes of Health Research and the University Hospital Foundation (Edmonton, Alberta, Canada) and the Health Research Council of New Zealand. Dr. Ezekowitz reports research grants from American Regent, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb/Pfizer, eko.ai, US2.ai, Merck, Novartis, Otsuka, Sanofi, and Servier and consulting fees from American Regent, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb/Pfizer, Merck, Novartis, Otsuka, Sanofi, and Servier.

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

A low-sodium diet was not associated with a reduction in future clinical events in a new study in ambulatory patients with heart failure. But there was a moderate benefit on quality of life and New York Heart Association (NYHA) functional class.

“The guidelines used to strongly recommend a reduction in sodium intake in heart failure patients, but this advice has backed off in recent years because of the lack of data. Most heart failure guidelines now do not make any recommendations on dietary sodium,” he said.

SODIUM-HF was a pragmatic, multinational, open-label, randomized trial conducted in six countries (Australia, Canada, Chile, Colombia, Mexico, and New Zealand), which included 809 patients (median age, 67 years) with chronic heart failure (NYHA functional class II–III) who were receiving optimally tolerated guideline-directed medical treatment. They were randomly assigned to usual care according to local guidelines or a low-sodium diet of less than 100 mmol (<1,500 mg/day). Patients with a baseline sodium intake of less than 1,500 mg/day were excluded.

In the intervention group, patients were asked to follow low-sodium menus developed by dietitians localized to each region. They also received behavioral counseling by trained dietitians or physicians or nurses.

Dietary sodium intake was assessed by using a 3-day food record (including 1 weekend day) at baseline, 6 months, and 12 months in both groups and, for the intervention group, also at 3 and 9 months to monitor and support dietary adherence.

Dr. Ezekowitz explained that although the best method for measuring sodium levels would normally be a 24-hour urine sodium, this would be impractical in a large clinical trial. In addition, he pointed out that urinary sodium is not an accurate measure of actual sodium levels in patients taking diuretics, so it is not a good measure to use in a heart failure population.

“The food record method of assessing sodium levels has been well validated; I think we measured it as accurately as we could have done,” he added.

Results showed that between baseline and 12 months, the median sodium intake decreased from 2,286 mg/day to 1,658 mg/day in the low-sodium group and from 2,119 mg/day to 2,073 mg/day in the usual care group. The median difference between groups was 415 mg/day at 12 months.

By 12 months, events comprising the primary outcome (hospitalization or emergency department visits due to cardiovascular causes or all-cause death) had occurred in 15% of patients in the low-sodium diet group and 17% of those in the usual care group (hazard ratio [HR], 0.89 [95% CI, 0.63 - 1.26]; P = .53).

All-cause death occurred in 6% of patients in the low-sodium diet group and 4% of those in the usual care group (HR, 1.38; P = .32). Cardiovascular-related hospitalization occurred in 10% of the low-sodium group and 12% of the usual care group (HR, 0.82; P = .36), and cardiovascular-related emergency department visits occurred in 4% of both groups (HR, 1.21; P = .60).

The absence of treatment effect for the primary outcome was consistent across most prespecified subgroups, including those with higher vs lower baseline sodium intake. But there was a suggestion of a greater reduction in the primary outcome in individuals younger than age 65 years than in those age 65 years and older.

Quality-of-life measures on the Kansas City Cardiomyopathy Questionnaire (KCCQ) suggested a benefit in the low-sodium group, with mean between-group differences in the change from baseline to 12 months of 3.38 points in the overall summary score, 3.29 points in the clinical summary score, and 3.77 points in the physical limitation score (all differences were statistically significant).

There was no significant difference in 6-minute-walk distance at 12 months between the low-sodium diet group and the usual care group.

NYHA functional class at 12 months differed significantly between groups; the low-sodium diet group had a greater likelihood of improving by one NYHA class than the usual care group (odds ratio, 0.59; P = .0061).

No safety events related to the study treatment were reported in either group.

Dr. Ezekowitz said that to investigate whether longer follow-up may show a difference in events, further analyses are planned at 2 years and 5 years.

Questions on food recall and blinding

Commenting on the findings at the late-breaking clinical trials session at the ACC meeting, Biykem Bozkurt, MD, professor of medicine at Baylor College of Medicine, Houston, congratulated Dr. Ezekowitz on conducting this trial.

“We have been chasing the holy grail of sodium reduction in heart failure for a very long time, so I have to commend you and your team for taking on this challenge, especially during the pandemic,” she said.

But Dr. Bozkurt questioned whether the intervention group actually had a meaningful sodium reduction given that this was measured by food recall and this may have been accounted for by under-reporting of certain food intakes.

Dr. Ezekowitz responded that patients acted as their own controls in that calorie intake, fluid intake, and weight were also assessed and did not change. “So I think we did have a meaningful reduction in sodium,” he said.

Dr. Bozkurt also queried whether the improvements in quality of life and functional status were reliable given that this was an unblinded study.

To this point, Dr. Ezekowitz pointed out that the KCCQ quality-of-life measure was a highly validated instrument and that improvements were seen in these measures at 3, 6, and 12 months. “It is not like these were spurious findings, so I think we have to look at this as a real result,” he argued.

Commenting on the study at an ACC press conference, Mary Norine Walsh, MD, director of the heart failure and cardiac transplantation programs at St. Vincent Heart Center in Indianapolis, said the trial had answered two important questions: that sodium reduction in heart failure may not reduce heart failure hospitalization/death but that patients feel better.

“I think we can safely tell patients that if they slip up a bit they may not end up in hospital,” she added.

This study was funded by the Canadian Institutes of Health Research and the University Hospital Foundation (Edmonton, Alberta, Canada) and the Health Research Council of New Zealand. Dr. Ezekowitz reports research grants from American Regent, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb/Pfizer, eko.ai, US2.ai, Merck, Novartis, Otsuka, Sanofi, and Servier and consulting fees from American Regent, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb/Pfizer, Merck, Novartis, Otsuka, Sanofi, and Servier.

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

A low-sodium diet was not associated with a reduction in future clinical events in a new study in ambulatory patients with heart failure. But there was a moderate benefit on quality of life and New York Heart Association (NYHA) functional class.

“The guidelines used to strongly recommend a reduction in sodium intake in heart failure patients, but this advice has backed off in recent years because of the lack of data. Most heart failure guidelines now do not make any recommendations on dietary sodium,” he said.

SODIUM-HF was a pragmatic, multinational, open-label, randomized trial conducted in six countries (Australia, Canada, Chile, Colombia, Mexico, and New Zealand), which included 809 patients (median age, 67 years) with chronic heart failure (NYHA functional class II–III) who were receiving optimally tolerated guideline-directed medical treatment. They were randomly assigned to usual care according to local guidelines or a low-sodium diet of less than 100 mmol (<1,500 mg/day). Patients with a baseline sodium intake of less than 1,500 mg/day were excluded.

In the intervention group, patients were asked to follow low-sodium menus developed by dietitians localized to each region. They also received behavioral counseling by trained dietitians or physicians or nurses.

Dietary sodium intake was assessed by using a 3-day food record (including 1 weekend day) at baseline, 6 months, and 12 months in both groups and, for the intervention group, also at 3 and 9 months to monitor and support dietary adherence.

Dr. Ezekowitz explained that although the best method for measuring sodium levels would normally be a 24-hour urine sodium, this would be impractical in a large clinical trial. In addition, he pointed out that urinary sodium is not an accurate measure of actual sodium levels in patients taking diuretics, so it is not a good measure to use in a heart failure population.

“The food record method of assessing sodium levels has been well validated; I think we measured it as accurately as we could have done,” he added.

Results showed that between baseline and 12 months, the median sodium intake decreased from 2,286 mg/day to 1,658 mg/day in the low-sodium group and from 2,119 mg/day to 2,073 mg/day in the usual care group. The median difference between groups was 415 mg/day at 12 months.

By 12 months, events comprising the primary outcome (hospitalization or emergency department visits due to cardiovascular causes or all-cause death) had occurred in 15% of patients in the low-sodium diet group and 17% of those in the usual care group (hazard ratio [HR], 0.89 [95% CI, 0.63 - 1.26]; P = .53).

All-cause death occurred in 6% of patients in the low-sodium diet group and 4% of those in the usual care group (HR, 1.38; P = .32). Cardiovascular-related hospitalization occurred in 10% of the low-sodium group and 12% of the usual care group (HR, 0.82; P = .36), and cardiovascular-related emergency department visits occurred in 4% of both groups (HR, 1.21; P = .60).

The absence of treatment effect for the primary outcome was consistent across most prespecified subgroups, including those with higher vs lower baseline sodium intake. But there was a suggestion of a greater reduction in the primary outcome in individuals younger than age 65 years than in those age 65 years and older.

Quality-of-life measures on the Kansas City Cardiomyopathy Questionnaire (KCCQ) suggested a benefit in the low-sodium group, with mean between-group differences in the change from baseline to 12 months of 3.38 points in the overall summary score, 3.29 points in the clinical summary score, and 3.77 points in the physical limitation score (all differences were statistically significant).

There was no significant difference in 6-minute-walk distance at 12 months between the low-sodium diet group and the usual care group.

NYHA functional class at 12 months differed significantly between groups; the low-sodium diet group had a greater likelihood of improving by one NYHA class than the usual care group (odds ratio, 0.59; P = .0061).

No safety events related to the study treatment were reported in either group.

Dr. Ezekowitz said that to investigate whether longer follow-up may show a difference in events, further analyses are planned at 2 years and 5 years.

Questions on food recall and blinding

Commenting on the findings at the late-breaking clinical trials session at the ACC meeting, Biykem Bozkurt, MD, professor of medicine at Baylor College of Medicine, Houston, congratulated Dr. Ezekowitz on conducting this trial.

“We have been chasing the holy grail of sodium reduction in heart failure for a very long time, so I have to commend you and your team for taking on this challenge, especially during the pandemic,” she said.

But Dr. Bozkurt questioned whether the intervention group actually had a meaningful sodium reduction given that this was measured by food recall and this may have been accounted for by under-reporting of certain food intakes.

Dr. Ezekowitz responded that patients acted as their own controls in that calorie intake, fluid intake, and weight were also assessed and did not change. “So I think we did have a meaningful reduction in sodium,” he said.

Dr. Bozkurt also queried whether the improvements in quality of life and functional status were reliable given that this was an unblinded study.

To this point, Dr. Ezekowitz pointed out that the KCCQ quality-of-life measure was a highly validated instrument and that improvements were seen in these measures at 3, 6, and 12 months. “It is not like these were spurious findings, so I think we have to look at this as a real result,” he argued.

Commenting on the study at an ACC press conference, Mary Norine Walsh, MD, director of the heart failure and cardiac transplantation programs at St. Vincent Heart Center in Indianapolis, said the trial had answered two important questions: that sodium reduction in heart failure may not reduce heart failure hospitalization/death but that patients feel better.

“I think we can safely tell patients that if they slip up a bit they may not end up in hospital,” she added.

This study was funded by the Canadian Institutes of Health Research and the University Hospital Foundation (Edmonton, Alberta, Canada) and the Health Research Council of New Zealand. Dr. Ezekowitz reports research grants from American Regent, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb/Pfizer, eko.ai, US2.ai, Merck, Novartis, Otsuka, Sanofi, and Servier and consulting fees from American Regent, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb/Pfizer, Merck, Novartis, Otsuka, Sanofi, and Servier.

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

Even very light alcohol intake is associated with an increased risk for cardiovascular disease, compared with not drinking at all, and the risk increases exponentially as alcohol intake rises, even at moderate levels, a new study shows.

“Our findings suggest that the observed benefit in individuals with light to moderate alcohol intake, which is consistently shown in epidemiological studies, is likely due to other positive lifestyle factors that are common in these individuals who drink lightly,” senior author Krishna Aragam, MD, Massachusetts General Hospital, Boston, told this news organization.

“Our results also showed that while all levels of alcohol were linked to increased risk of cardiovascular disease, the association was not linear. Rather, light alcohol intake was associated with rather modest risk increases, but there were exponential increases in cardiovascular risk with increasing amounts of alcohol consumption,” he said.

As the risk gradient appeared to increase quite sharply even between 1 and 2 drinks per day, Dr. Aragam suggested that what might be regarded as safe levels of drinking may trend downward in the future.

Kirby Hamilton/iStockphoto

They also conducted genetic analyses to examine the effect of alcohol and cardiovascular disease.   

Dr. Aragam explained that previous work has shown good evidence, in individuals who choose to drink, that several relevant genetic variants predict levels of alcohol consumption quite accurately.

“Mendelian randomization using these gene variants allows for stronger inferences about potential causality than do observational studies, as they are less affected by confounding factors,” he noted.

Newer techniques in Mendelian randomization in which data on several gene variants linked to alcohol consumption are combined into a score allow for a greater understanding of the risk linked to different amount of alcohol intake, he added.

In these Mendelian randomization analyses, a 1-standard deviation increase in genetically predicted alcohol consumption was associated with 1.3-fold higher risk of hypertension (P < .001) and 1.4-fold higher risk of coronary artery disease (P = .006).

Further analyses suggested nonlinear associations between alcohol consumption and both hypertension and coronary artery disease; light alcohol intake was associated with minimal increases in cardiovascular risk, whereas heavier consumption was associated with exponential increases in risk of both clinical and subclinical cardiovascular disease.

These results were replicated in a second database of 30,716 individuals from the Mass General Brigham Biobank.

“The findings of this study suggest that the observed cardioprotective effects of light to moderate alcohol intake may be largely mediated by confounding lifestyle factors,” the researchers conclude. “Genetic analyses suggest causal associations between alcohol intake and cardiovascular disease but with unequal and exponential increases in risk at greater levels of intake, which should be accounted for in health recommendations around the habitual consumption of alcohol.”

What is an acceptable level? 

“Specifically, our results suggest that consuming as many as 7 drinks per week is associated with relatively modest increases in cardiovascular risk,” they write.

But they point out that there are unequal increases in cardiovascular risk when progressing from 0 to 7 versus 7 to 14 drinks per week in both men and women.

“Although risk thresholds are inherently somewhat subjective, these findings again bring into question whether an average consumption of 2 drinks per day (14 drinks per week) should be designated a low-risk behavior,” they say.

“Furthermore, as several-fold increases in risk were observed for those consuming 21 or more drinks per week, our results emphasize the importance of aggressive efforts to reduce alcohol intake among heavy drinkers,” they add.

Dr. Aragam elaborated: “Our data suggest that reducing alcohol intake will reduce cardiovascular risk in all individuals, but the extent of the relative risk reduction is quite different depending on the current levels of consumption. For the same absolute reduction in alcohol intake, the gains in terms of reduction in cardiovascular risk will be more pronounced in those who drink heavily and will be more modest in those who drink at a light level.”

The results also suggest that while all levels of alcohol intake increase cardiovascular risk, there are low levels of alcohol consumption that do not carry major elevations in risk, but these are probably lower than those currently recommended, Dr. Aragam pointed out. 

“This doesn’t mean that everyone has to give up drinking alcohol completely, just that you shouldn’t consume with the goal of improving cardiovascular health. In fact, our analyses suggest that in an otherwise healthy person, up to 1 drink per day may not pose outsized risks,” he said. “And, even in a less healthy person who might be smoking, eating poorly, and drinking up to 1 drink per day, it may be a higher priority to focus on smoking cessation and diet than cutting back further on alcohol.”

“Beyond that amount, though, the jury is still out. Our models suggested marked increases in risk even between 1 and 2 drinks per day, and of course even greater risk increases beyond that. So, it’s probably worth revisiting what one might consider a ‘safe’ amount within the moderate drinking categories. The conservative move for now might be to advise a limit of 1 drink per day,” he said.   

Dr. Aragam is supported by grants from the National Institutes of Health and the American Heart Association. He reports receiving speaking fees from the Novartis Institute for Biomedical Research.

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

Even very light alcohol intake is associated with an increased risk for cardiovascular disease, compared with not drinking at all, and the risk increases exponentially as alcohol intake rises, even at moderate levels, a new study shows.

“Our findings suggest that the observed benefit in individuals with light to moderate alcohol intake, which is consistently shown in epidemiological studies, is likely due to other positive lifestyle factors that are common in these individuals who drink lightly,” senior author Krishna Aragam, MD, Massachusetts General Hospital, Boston, told this news organization.

“Our results also showed that while all levels of alcohol were linked to increased risk of cardiovascular disease, the association was not linear. Rather, light alcohol intake was associated with rather modest risk increases, but there were exponential increases in cardiovascular risk with increasing amounts of alcohol consumption,” he said.

As the risk gradient appeared to increase quite sharply even between 1 and 2 drinks per day, Dr. Aragam suggested that what might be regarded as safe levels of drinking may trend downward in the future.

Kirby Hamilton/iStockphoto

They also conducted genetic analyses to examine the effect of alcohol and cardiovascular disease.   

Dr. Aragam explained that previous work has shown good evidence, in individuals who choose to drink, that several relevant genetic variants predict levels of alcohol consumption quite accurately.

“Mendelian randomization using these gene variants allows for stronger inferences about potential causality than do observational studies, as they are less affected by confounding factors,” he noted.

Newer techniques in Mendelian randomization in which data on several gene variants linked to alcohol consumption are combined into a score allow for a greater understanding of the risk linked to different amount of alcohol intake, he added.

In these Mendelian randomization analyses, a 1-standard deviation increase in genetically predicted alcohol consumption was associated with 1.3-fold higher risk of hypertension (P < .001) and 1.4-fold higher risk of coronary artery disease (P = .006).

Further analyses suggested nonlinear associations between alcohol consumption and both hypertension and coronary artery disease; light alcohol intake was associated with minimal increases in cardiovascular risk, whereas heavier consumption was associated with exponential increases in risk of both clinical and subclinical cardiovascular disease.

These results were replicated in a second database of 30,716 individuals from the Mass General Brigham Biobank.

“The findings of this study suggest that the observed cardioprotective effects of light to moderate alcohol intake may be largely mediated by confounding lifestyle factors,” the researchers conclude. “Genetic analyses suggest causal associations between alcohol intake and cardiovascular disease but with unequal and exponential increases in risk at greater levels of intake, which should be accounted for in health recommendations around the habitual consumption of alcohol.”

What is an acceptable level? 

“Specifically, our results suggest that consuming as many as 7 drinks per week is associated with relatively modest increases in cardiovascular risk,” they write.

But they point out that there are unequal increases in cardiovascular risk when progressing from 0 to 7 versus 7 to 14 drinks per week in both men and women.

“Although risk thresholds are inherently somewhat subjective, these findings again bring into question whether an average consumption of 2 drinks per day (14 drinks per week) should be designated a low-risk behavior,” they say.

“Furthermore, as several-fold increases in risk were observed for those consuming 21 or more drinks per week, our results emphasize the importance of aggressive efforts to reduce alcohol intake among heavy drinkers,” they add.

Dr. Aragam elaborated: “Our data suggest that reducing alcohol intake will reduce cardiovascular risk in all individuals, but the extent of the relative risk reduction is quite different depending on the current levels of consumption. For the same absolute reduction in alcohol intake, the gains in terms of reduction in cardiovascular risk will be more pronounced in those who drink heavily and will be more modest in those who drink at a light level.”

The results also suggest that while all levels of alcohol intake increase cardiovascular risk, there are low levels of alcohol consumption that do not carry major elevations in risk, but these are probably lower than those currently recommended, Dr. Aragam pointed out. 

“This doesn’t mean that everyone has to give up drinking alcohol completely, just that you shouldn’t consume with the goal of improving cardiovascular health. In fact, our analyses suggest that in an otherwise healthy person, up to 1 drink per day may not pose outsized risks,” he said. “And, even in a less healthy person who might be smoking, eating poorly, and drinking up to 1 drink per day, it may be a higher priority to focus on smoking cessation and diet than cutting back further on alcohol.”

“Beyond that amount, though, the jury is still out. Our models suggested marked increases in risk even between 1 and 2 drinks per day, and of course even greater risk increases beyond that. So, it’s probably worth revisiting what one might consider a ‘safe’ amount within the moderate drinking categories. The conservative move for now might be to advise a limit of 1 drink per day,” he said.   

Dr. Aragam is supported by grants from the National Institutes of Health and the American Heart Association. He reports receiving speaking fees from the Novartis Institute for Biomedical Research.

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

Even very light alcohol intake is associated with an increased risk for cardiovascular disease, compared with not drinking at all, and the risk increases exponentially as alcohol intake rises, even at moderate levels, a new study shows.

“Our findings suggest that the observed benefit in individuals with light to moderate alcohol intake, which is consistently shown in epidemiological studies, is likely due to other positive lifestyle factors that are common in these individuals who drink lightly,” senior author Krishna Aragam, MD, Massachusetts General Hospital, Boston, told this news organization.

“Our results also showed that while all levels of alcohol were linked to increased risk of cardiovascular disease, the association was not linear. Rather, light alcohol intake was associated with rather modest risk increases, but there were exponential increases in cardiovascular risk with increasing amounts of alcohol consumption,” he said.

As the risk gradient appeared to increase quite sharply even between 1 and 2 drinks per day, Dr. Aragam suggested that what might be regarded as safe levels of drinking may trend downward in the future.

Kirby Hamilton/iStockphoto

They also conducted genetic analyses to examine the effect of alcohol and cardiovascular disease.   

Dr. Aragam explained that previous work has shown good evidence, in individuals who choose to drink, that several relevant genetic variants predict levels of alcohol consumption quite accurately.

“Mendelian randomization using these gene variants allows for stronger inferences about potential causality than do observational studies, as they are less affected by confounding factors,” he noted.

Newer techniques in Mendelian randomization in which data on several gene variants linked to alcohol consumption are combined into a score allow for a greater understanding of the risk linked to different amount of alcohol intake, he added.

In these Mendelian randomization analyses, a 1-standard deviation increase in genetically predicted alcohol consumption was associated with 1.3-fold higher risk of hypertension (P < .001) and 1.4-fold higher risk of coronary artery disease (P = .006).

Further analyses suggested nonlinear associations between alcohol consumption and both hypertension and coronary artery disease; light alcohol intake was associated with minimal increases in cardiovascular risk, whereas heavier consumption was associated with exponential increases in risk of both clinical and subclinical cardiovascular disease.

These results were replicated in a second database of 30,716 individuals from the Mass General Brigham Biobank.

“The findings of this study suggest that the observed cardioprotective effects of light to moderate alcohol intake may be largely mediated by confounding lifestyle factors,” the researchers conclude. “Genetic analyses suggest causal associations between alcohol intake and cardiovascular disease but with unequal and exponential increases in risk at greater levels of intake, which should be accounted for in health recommendations around the habitual consumption of alcohol.”

What is an acceptable level? 

“Specifically, our results suggest that consuming as many as 7 drinks per week is associated with relatively modest increases in cardiovascular risk,” they write.

But they point out that there are unequal increases in cardiovascular risk when progressing from 0 to 7 versus 7 to 14 drinks per week in both men and women.

“Although risk thresholds are inherently somewhat subjective, these findings again bring into question whether an average consumption of 2 drinks per day (14 drinks per week) should be designated a low-risk behavior,” they say.

“Furthermore, as several-fold increases in risk were observed for those consuming 21 or more drinks per week, our results emphasize the importance of aggressive efforts to reduce alcohol intake among heavy drinkers,” they add.

Dr. Aragam elaborated: “Our data suggest that reducing alcohol intake will reduce cardiovascular risk in all individuals, but the extent of the relative risk reduction is quite different depending on the current levels of consumption. For the same absolute reduction in alcohol intake, the gains in terms of reduction in cardiovascular risk will be more pronounced in those who drink heavily and will be more modest in those who drink at a light level.”

The results also suggest that while all levels of alcohol intake increase cardiovascular risk, there are low levels of alcohol consumption that do not carry major elevations in risk, but these are probably lower than those currently recommended, Dr. Aragam pointed out. 

“This doesn’t mean that everyone has to give up drinking alcohol completely, just that you shouldn’t consume with the goal of improving cardiovascular health. In fact, our analyses suggest that in an otherwise healthy person, up to 1 drink per day may not pose outsized risks,” he said. “And, even in a less healthy person who might be smoking, eating poorly, and drinking up to 1 drink per day, it may be a higher priority to focus on smoking cessation and diet than cutting back further on alcohol.”

“Beyond that amount, though, the jury is still out. Our models suggested marked increases in risk even between 1 and 2 drinks per day, and of course even greater risk increases beyond that. So, it’s probably worth revisiting what one might consider a ‘safe’ amount within the moderate drinking categories. The conservative move for now might be to advise a limit of 1 drink per day,” he said.   

Dr. Aragam is supported by grants from the National Institutes of Health and the American Heart Association. He reports receiving speaking fees from the Novartis Institute for Biomedical Research.

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

Regardless of the pandemic’s sometimes mercurial behavior, the cardiology community appears set to reclaim valued traditions perhaps taken for granted in the pre-COVID era.

They include the bustling scientific congress and its myriad educational and networking prospects, along with pleiotropic effects like unplanned reunions with colleagues and catching up face-to-face with old friends.

That seems evident in the growing number of registrants for live attendance at at the annual scientific sessions of the American College of Cardiology, set for this Saturday through Monday in Washington as well as virtually, for a global reach that was unattainable in the pre-COVID era.

Registrations had hit the 11,000 mark and were picking up speed in recent weeks, ACC 2022 cochair Pamela B. Morris, MD, Medical University of South Carolina, Charleston, said at a mid-March presentation to the media.

They had reached about 12,880 and were still climbing a week before the conference, the ACC confirmed to this news organization. By then the professional registration had surpassed 9,900, of whom more than two-thirds reported plans to attend in person.

Dr. Morris said there had been 117 international submissions for what turned out to be 39 coveted spots on the meeting’s Late-Breaking Clinical Trial (LBCT) and Featured Clinical Research agenda spread across eight separate sessions.

On-site participants at the Walter E. Washington Convention Center should head for the Main Tent in Hall D for all LBCT presentations; venues for the Featured Clinical Research sessions are as noted below. Their real-time virtual equivalents will reside on the online platform’s Hot Topics channel. All noted session times are Eastern Daylight Time.
 

Saturday, April 2, 9:30 a.m.–10:30 a.m. Joint American College of Cardiology/Journal of the American College of Cardiology LBCT (I)

Leading off the conference’s first LBCT session, the randomized VALOR-HCM trial explored whether 16 weeks of mavacamten (MyoKardia) could help patients with severe obstructive hypertrophic cardiomyopathy (HCM) avoid septal reduction therapy, either surgical or by alcohol ablation.

The 22-center VALOR-HCM trial with an estimated enrollment of 100 follows EXPLORER-HCM, which in 2020 suggested the novel myosin-inhibiting agent could improve symptoms, exercise capacity, cardiac remodeling, and quality of life in such patients.

Simply advising people with heart failure (HF) to consume less salt is one thing, but it’s another to show them clinical trial evidence that it might help keep them out of the hospital. The SODIUM-HF (Study of Dietary Intervention Under 100 mmol in Heart Failure) study, conducted at 27 sites in six countries, sought to provide that evidence.

The trial randomly assigned 1,000 patients with NYHA class 2-3 HF to consume no more than 1,500 mg/day in sodium or to receive standard advice to limit sodium intake, and followed them for a year for the endpoint of death from any cause, cardiovascular (CV) hospitalization, or CV emergency department visit.

SODIUM-HF “may provide a rigorous evidence base for sodium restriction in patients with heart failure and may truly change our practice and how we recommend dietary modification,” ACC 2022 vice chair Douglas E. Drachman, MD, Massachusetts General Hospital, Boston, said at the media presentation.

In the same session, the CHAP (Chronic Hypertension and Pregnancy) study explored whether blood pressure (BP) control in pregnant women with new or untreated chronic hypertension could help avert preeclampsia, poor fetal outcomes, and other adverse events.

CHAP assigned about 2,400 women to receive either stepwise antihypertensive therapy to a BP goal of 140/90 mm Hg or lower or no such meds unless their BP reached or exceeded 160/105 mm Hg. Stepwise therapy featured either labetalol or extended-release nifedipine to start, the other agent added as necessary.

The LBCT block also includes the POISE-3 (Perioperative Ischemic Evaluation-3) comparison of the hemostatic agent tranexamic acid vs. placebo in nearly 10,000 patients undergoing noncardiac surgery. A separate randomization of the same cohort, to be reported at a Monday LBCT session, compared pre- and perioperative BP-control strategies.
 

Saturday, April 2, 12:00 p.m.–1:15 p.m. Featured Clinical Research I. Room 143A

This session features a subgroup analysis by age from the REVERSE-IT trial, which had previously showcased the monoclonal antibody bentracimab (PhaseBio Pharmaceuticals) for its ability to reverse the antiplatelet effects of ticagrelor.

REVERSE-IT is accompanied on the schedule by several secondary-endpoint presentations from trials whose primary outcomes have already been presented at meetings or in the journals.

They include the SCORED trial of sotagliflozin in patients with diabetes and chronic kidney disease (CKD); COMPLETE, which explored complete revascularization of multivessel coronary disease at primary stenting; and the FAME-3 comparison of coronary bypass surgery (CABG) vs. percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) readings.

The session is to conclude with EDIT-CMD, which was a small, randomized assessment of diltiazem for improving microvascular dysfunction in patients with chronic angina despite nonobstructive coronary disease.
 

Sunday, April 3, 8:00 a.m.–9:15 a.m. Joint American College of Cardiology/Journal of the American Medical Association LBCT (II)

The SuperWIN (Supermarket Web Intervention) study tested an innovative strategy for community-based promotion of healthy lifestyle choices: point-of-purchase dietary education for grocery shoppers with an online instructional component, and follow-up to determine whether it influenced future food choices.

“Dietary interventions are notoriously difficult for us to implement, let alone to study scientifically,” Dr. Drachman observed. “So we think that there may be opportunity for dietary interventions to be best implemented at grocery stores where people are doing their shopping for food.”

SuperWIN compared supermarket shoppers with at least one CV risk factor who participated in the education intervention to a nonintervention control group for any changes in their DASH scores. The scores reflected consistency with the venerable DASH diet based on participants’ food purchases over 3 months.

In the same session, the MITIGATE trial explored whether daily administration of icosapent ethyl (Vascepa) might cut the risk of upper respiratory infection (especially from SARS-CoV-2 or seasonal influenza virus) in persons 50 or older with a history of clinical coronary, neurovascular, or peripheral vascular disease or revascularization. The trial has an estimated enrollment of 39,600.

Accompanying SuperWIN and MITIGATE are studies of several dyslipidemia drugs, including the discontinued antisense agent vupanorsen (Pfizer), as tested in TRANSLATE-TIMI 70;  the PCSK9 inhibitor alirocumab (Praluent), explored for its effects on coronary plaque volume and composition in the PACMAN-AMI trial; and the APOLLO trial, a phase 1 evaluation of SLN360 (Silence Therapeutics), a short interfering ribonucleic acid (siRNA) that suppresses the molecular machinery in the liver that produces lipoprotein(a), or Lp(a).

The 32-patient APOLLO trial’s recently released top-line results suggested that SLN360 at varying dosages reduced Lp(a) levels by about one-half to more than 90%. Although elevated Lp(a) is known to track with CV risk, it remains to be shown whether dropping Lp(a) levels pharmacologically is protective.
 

Sunday, April 3, 9:45 a.m.–11:00 a.m. Joint American College of Cardiology/New England Journal of Medicine LBCT (III)

The meeting’s all-HF late-breaker session includes the METEORIC-HF trial, which compared the myotropic agent omecamtiv mecarbil (Cytokinetics) against placebo for effects on exercise performance over 20 weeks. The trial entered 276 patients with HF with reduced ejection fraction (HFrEF) and reduced peak VO₂.

The GALACTIC-HF trial had previously suggested that the drug improved the risk of HF-related events or CV death in more than 8000 patients with HFrEF, those with the lowest ejection fractions benefiting the most.

This block of trials also features DIAMOND, the latest trial with a gemologic name to look at the potassium sequestrant patiromer (Veltassa) for any protection against hyperkalemia, a familiar side effect of renin-angiotensin-aldosterone inhibitors. DIAMOND tested patiromer in 878 patients with HFrEF who were on beta-blockers and other HF-appropriate medications and had a history of drug-associated hyperkalemia.

Previously, the AMBER trial of patients with CKD or refractory hypertension on spironolactone had suggested the drug might be protective enough against hyperkalemia to allow higher and more consistent dosing of BP-lowering agents.

Also in the session: the randomized IVVE (Influenza Vaccine to Prevent Adverse Vascular Events) trial, with an estimated 5,000 patients with HF in Africa, Asia, and the Middle East; PROMPT-HF, with a projected 1,310 HF patients and billed as a cluster-randomized pragmatic trial of a strategy for improving guideline-directed outpatient medical therapy; and MAVA-LTE, the long-term extension study of an estimated 310 patients who were in the MAVERICK-HCM and EXPLORER-HCM mavacamten trials.
 

Sunday, April 3, 12:15–1:30 p.m. Featured Clinical Research II. Main Tent, Hall D

The arrhythmia-centric session includes PARTITA, with its estimated 590 patients with primary- or secondary-prevention implantable cardioverter-defibrillators (ICDs). The trial followed them initially for burden of untreated nonsustained ventricular tachycardia (VT) or events treated with anti-tachycardia pacing. Then it randomly assigned those who experienced a first appropriate ICD shock to either immediate VT ablation or standard care. The latter included ablation on next occurrence of arrhythmic storm.

Investigational oral factor XIa inhibitors, viewed by many as potentially safer as anticoagulants than contemporary oral inhibitors of factor Xa, are now on the scene and include milvexian (Bristol-Myers Squibb/Janssen) and, lately, asundexian (BAY 2433334; Bayer). The latter agent was compared to the factor Xa inhibitor apixaban (Eliquis) in 753 patients with AF in the phase 2 PACIFIC-AF trial, which looked at the newer drug’s safety and optimal dosing.

Also on the bill: a long-term follow-up of the mAFA-2 (Mobile AF Application 2) extension study, which explored the value of a smartphone-based atrial fibrillation (AF) screening app for improving risk of AF-related events; a presentation billed as “Residual Leaks Post Left Atrial Appendage Occlusion”; and one that declares “low rates of guideline-directed care” to be “associated with higher mortality” in patients with pacemakers or ICDs.
 

Monday, April 4, 8:30 a.m.–9:45 a.m. LBCT IV

This session is to open with the PROTECT trial, which sought to determine whether perioperative “aggressive warming” may be cardioprotective in patients with CV risk factors undergoing noncardiac surgery. Its estimated 5,100 patients were randomly assigned to a procedure that achieves normothermia, that is 37° C (98.6° F), vs. standard care in which patients’ core temperature may decline to no further than 35.5° C (95.9° F).

Next on the list are a second POISE-3 comparison of BP-control strategies comparing hypotension avoidance vs. hypertension avoidance in patients undergoing noncardiac surgery; the pivotal CLASP 2 TR trial of patients with symptomatic tricuspid regurgitation on optimal medical therapy with vs. without treatment with the Edwards PASCAL Transcatheter Repair System; and one said to provide “insights from the Corevalve US Pivotal and SURTAVI trials” on 5-year incidence, timing, and predictors of hemodynamic valve deterioration transcatheter and surgical aortic bioprostheses.”

Rounding out the block of presentations: the ADAPT-TAVR comparison of the factor Xa inhibitor edoxaban (Lixiana) to dual-antiplatelet therapy for prevention of leaflet thrombosis after successful transcatheter aortic valve replacement (TAVR). The 235-patient trial was conducted at five centers in South Korea, Hong Kong, and Taiwan.
 

Monday, April 4, 11:00–12:15 p.m. LBCT V

This session includes the FLAVOUR randomized comparison of PCI guided by either FFR or intravascular ultrasound (IVUS) in 1,700 patients with 40%-70% stenoses. The patients from centers in China and South Korea were followed for death from any cause, MI, or any repeat revascularization at 24 months.

Also scheduled: the 2-year report on 4,000 patients with ST-segment elevation MI (STEMI) in the ACC-sponsored quality improvement program GHATI (Global Heart Attack Treatment Initiative); the GIPS-4 myocardial protection study of an estimated 380 patients with STEMI assigned to receive pre- and post-PCI infusions of sodium thiosulfate or placebo, with infarct size at 4 months as the primary endpoint; and a randomized test of an arrhythmia-monitoring implant for influence on clinical outcomes in 802 patients with a history of MI but no pacemaker or ICD indication, called BIO-GUARD-MI,

Last in the session: the Chocolate Touch Study of peripheral-artery angioplasty using a drug-coated balloon (DCB) with a confectionery name that treats lesions not with theobromine, but the antiproliferative mainstay paclitaxel.

The randomized comparison of the Chocolate Touch DCB (TriReme Medical) and the more established Lutonix DCB (Bard) assigned a projected 585 patients with symptomatic peripheral vascular disease to treatment of superficial femoral or popliteal artery lesions with one of the two paclitaxel-coated balloon catheters.
 

Monday, April 4, 12:45–2 p.m. Featured Clinical Research III. Room 143A 

The final session features five subgroup analyses or other updates from trials that have already reported their primary outcomes. Among them is the SPYRAL HTN-ON MED trial, which helped to revitalize hopes for renal denervation therapy as a catheter-based treatment for drug-resistant hypertension by showing significant effects on both systolic and diastolic blood pressure. The new data follow the trial’s more than 400 patients out to 3 years.

There is also a symptom and quality-of-life analysis from the 530-patient EMPULSE trial of 530 patients with stabilized acute HF assigned in-hospital to start on empagliflozin (Jardiance) or placebo. The trial made a splash last year when it reported a significant improvement in risk for death or HF rehospitalization for its patients put on the SGLT2 inhibitor.

A secondary analysis from CANTOS is also featured; the trial had randomly assigned more than 10,000 patients with recent acute MI and elevated C-reactive protein (CRP) levels to receive or not receive the anti-inflammatory canakinumab (Ilaris). Those assigned to active therapy showed benefits for a range of outcomes, including CV mortality and stroke, but no decreases in cholesterol levels. Billing for the new CANTOS analysis promises insights on the “differential impact of residual inflammatory risk and residual cholesterol risk among atherosclerosis patients with and without chronic kidney disease.”

The session also features “trends and final results” from the NACMI (North American COVID-19 Myocardial Infarction) registry, which had shown excellent primary-PCI results without compromise of door-to-balloon times in patients with confirmed SARS-CoV-2 infection; and a FIDELITY analysis of cardiorenal endpoints by history of CV disease in the study’s more than 13,000 patients with diabetes and CKD assigned to placebo or finerenone (Kerendia), a mineralocorticoid receptor antagonist.

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

Regardless of the pandemic’s sometimes mercurial behavior, the cardiology community appears set to reclaim valued traditions perhaps taken for granted in the pre-COVID era.

They include the bustling scientific congress and its myriad educational and networking prospects, along with pleiotropic effects like unplanned reunions with colleagues and catching up face-to-face with old friends.

That seems evident in the growing number of registrants for live attendance at at the annual scientific sessions of the American College of Cardiology, set for this Saturday through Monday in Washington as well as virtually, for a global reach that was unattainable in the pre-COVID era.

Registrations had hit the 11,000 mark and were picking up speed in recent weeks, ACC 2022 cochair Pamela B. Morris, MD, Medical University of South Carolina, Charleston, said at a mid-March presentation to the media.

They had reached about 12,880 and were still climbing a week before the conference, the ACC confirmed to this news organization. By then the professional registration had surpassed 9,900, of whom more than two-thirds reported plans to attend in person.

Dr. Morris said there had been 117 international submissions for what turned out to be 39 coveted spots on the meeting’s Late-Breaking Clinical Trial (LBCT) and Featured Clinical Research agenda spread across eight separate sessions.

On-site participants at the Walter E. Washington Convention Center should head for the Main Tent in Hall D for all LBCT presentations; venues for the Featured Clinical Research sessions are as noted below. Their real-time virtual equivalents will reside on the online platform’s Hot Topics channel. All noted session times are Eastern Daylight Time.
 

Saturday, April 2, 9:30 a.m.–10:30 a.m. Joint American College of Cardiology/Journal of the American College of Cardiology LBCT (I)

Leading off the conference’s first LBCT session, the randomized VALOR-HCM trial explored whether 16 weeks of mavacamten (MyoKardia) could help patients with severe obstructive hypertrophic cardiomyopathy (HCM) avoid septal reduction therapy, either surgical or by alcohol ablation.

The 22-center VALOR-HCM trial with an estimated enrollment of 100 follows EXPLORER-HCM, which in 2020 suggested the novel myosin-inhibiting agent could improve symptoms, exercise capacity, cardiac remodeling, and quality of life in such patients.

Simply advising people with heart failure (HF) to consume less salt is one thing, but it’s another to show them clinical trial evidence that it might help keep them out of the hospital. The SODIUM-HF (Study of Dietary Intervention Under 100 mmol in Heart Failure) study, conducted at 27 sites in six countries, sought to provide that evidence.

The trial randomly assigned 1,000 patients with NYHA class 2-3 HF to consume no more than 1,500 mg/day in sodium or to receive standard advice to limit sodium intake, and followed them for a year for the endpoint of death from any cause, cardiovascular (CV) hospitalization, or CV emergency department visit.

SODIUM-HF “may provide a rigorous evidence base for sodium restriction in patients with heart failure and may truly change our practice and how we recommend dietary modification,” ACC 2022 vice chair Douglas E. Drachman, MD, Massachusetts General Hospital, Boston, said at the media presentation.

In the same session, the CHAP (Chronic Hypertension and Pregnancy) study explored whether blood pressure (BP) control in pregnant women with new or untreated chronic hypertension could help avert preeclampsia, poor fetal outcomes, and other adverse events.

CHAP assigned about 2,400 women to receive either stepwise antihypertensive therapy to a BP goal of 140/90 mm Hg or lower or no such meds unless their BP reached or exceeded 160/105 mm Hg. Stepwise therapy featured either labetalol or extended-release nifedipine to start, the other agent added as necessary.

The LBCT block also includes the POISE-3 (Perioperative Ischemic Evaluation-3) comparison of the hemostatic agent tranexamic acid vs. placebo in nearly 10,000 patients undergoing noncardiac surgery. A separate randomization of the same cohort, to be reported at a Monday LBCT session, compared pre- and perioperative BP-control strategies.
 

Saturday, April 2, 12:00 p.m.–1:15 p.m. Featured Clinical Research I. Room 143A

This session features a subgroup analysis by age from the REVERSE-IT trial, which had previously showcased the monoclonal antibody bentracimab (PhaseBio Pharmaceuticals) for its ability to reverse the antiplatelet effects of ticagrelor.

REVERSE-IT is accompanied on the schedule by several secondary-endpoint presentations from trials whose primary outcomes have already been presented at meetings or in the journals.

They include the SCORED trial of sotagliflozin in patients with diabetes and chronic kidney disease (CKD); COMPLETE, which explored complete revascularization of multivessel coronary disease at primary stenting; and the FAME-3 comparison of coronary bypass surgery (CABG) vs. percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) readings.

The session is to conclude with EDIT-CMD, which was a small, randomized assessment of diltiazem for improving microvascular dysfunction in patients with chronic angina despite nonobstructive coronary disease.
 

Sunday, April 3, 8:00 a.m.–9:15 a.m. Joint American College of Cardiology/Journal of the American Medical Association LBCT (II)

The SuperWIN (Supermarket Web Intervention) study tested an innovative strategy for community-based promotion of healthy lifestyle choices: point-of-purchase dietary education for grocery shoppers with an online instructional component, and follow-up to determine whether it influenced future food choices.

“Dietary interventions are notoriously difficult for us to implement, let alone to study scientifically,” Dr. Drachman observed. “So we think that there may be opportunity for dietary interventions to be best implemented at grocery stores where people are doing their shopping for food.”

SuperWIN compared supermarket shoppers with at least one CV risk factor who participated in the education intervention to a nonintervention control group for any changes in their DASH scores. The scores reflected consistency with the venerable DASH diet based on participants’ food purchases over 3 months.

In the same session, the MITIGATE trial explored whether daily administration of icosapent ethyl (Vascepa) might cut the risk of upper respiratory infection (especially from SARS-CoV-2 or seasonal influenza virus) in persons 50 or older with a history of clinical coronary, neurovascular, or peripheral vascular disease or revascularization. The trial has an estimated enrollment of 39,600.

Accompanying SuperWIN and MITIGATE are studies of several dyslipidemia drugs, including the discontinued antisense agent vupanorsen (Pfizer), as tested in TRANSLATE-TIMI 70;  the PCSK9 inhibitor alirocumab (Praluent), explored for its effects on coronary plaque volume and composition in the PACMAN-AMI trial; and the APOLLO trial, a phase 1 evaluation of SLN360 (Silence Therapeutics), a short interfering ribonucleic acid (siRNA) that suppresses the molecular machinery in the liver that produces lipoprotein(a), or Lp(a).

The 32-patient APOLLO trial’s recently released top-line results suggested that SLN360 at varying dosages reduced Lp(a) levels by about one-half to more than 90%. Although elevated Lp(a) is known to track with CV risk, it remains to be shown whether dropping Lp(a) levels pharmacologically is protective.
 

Sunday, April 3, 9:45 a.m.–11:00 a.m. Joint American College of Cardiology/New England Journal of Medicine LBCT (III)

The meeting’s all-HF late-breaker session includes the METEORIC-HF trial, which compared the myotropic agent omecamtiv mecarbil (Cytokinetics) against placebo for effects on exercise performance over 20 weeks. The trial entered 276 patients with HF with reduced ejection fraction (HFrEF) and reduced peak VO₂.

The GALACTIC-HF trial had previously suggested that the drug improved the risk of HF-related events or CV death in more than 8000 patients with HFrEF, those with the lowest ejection fractions benefiting the most.

This block of trials also features DIAMOND, the latest trial with a gemologic name to look at the potassium sequestrant patiromer (Veltassa) for any protection against hyperkalemia, a familiar side effect of renin-angiotensin-aldosterone inhibitors. DIAMOND tested patiromer in 878 patients with HFrEF who were on beta-blockers and other HF-appropriate medications and had a history of drug-associated hyperkalemia.

Previously, the AMBER trial of patients with CKD or refractory hypertension on spironolactone had suggested the drug might be protective enough against hyperkalemia to allow higher and more consistent dosing of BP-lowering agents.

Also in the session: the randomized IVVE (Influenza Vaccine to Prevent Adverse Vascular Events) trial, with an estimated 5,000 patients with HF in Africa, Asia, and the Middle East; PROMPT-HF, with a projected 1,310 HF patients and billed as a cluster-randomized pragmatic trial of a strategy for improving guideline-directed outpatient medical therapy; and MAVA-LTE, the long-term extension study of an estimated 310 patients who were in the MAVERICK-HCM and EXPLORER-HCM mavacamten trials.
 

Sunday, April 3, 12:15–1:30 p.m. Featured Clinical Research II. Main Tent, Hall D

The arrhythmia-centric session includes PARTITA, with its estimated 590 patients with primary- or secondary-prevention implantable cardioverter-defibrillators (ICDs). The trial followed them initially for burden of untreated nonsustained ventricular tachycardia (VT) or events treated with anti-tachycardia pacing. Then it randomly assigned those who experienced a first appropriate ICD shock to either immediate VT ablation or standard care. The latter included ablation on next occurrence of arrhythmic storm.

Investigational oral factor XIa inhibitors, viewed by many as potentially safer as anticoagulants than contemporary oral inhibitors of factor Xa, are now on the scene and include milvexian (Bristol-Myers Squibb/Janssen) and, lately, asundexian (BAY 2433334; Bayer). The latter agent was compared to the factor Xa inhibitor apixaban (Eliquis) in 753 patients with AF in the phase 2 PACIFIC-AF trial, which looked at the newer drug’s safety and optimal dosing.

Also on the bill: a long-term follow-up of the mAFA-2 (Mobile AF Application 2) extension study, which explored the value of a smartphone-based atrial fibrillation (AF) screening app for improving risk of AF-related events; a presentation billed as “Residual Leaks Post Left Atrial Appendage Occlusion”; and one that declares “low rates of guideline-directed care” to be “associated with higher mortality” in patients with pacemakers or ICDs.
 

Monday, April 4, 8:30 a.m.–9:45 a.m. LBCT IV

This session is to open with the PROTECT trial, which sought to determine whether perioperative “aggressive warming” may be cardioprotective in patients with CV risk factors undergoing noncardiac surgery. Its estimated 5,100 patients were randomly assigned to a procedure that achieves normothermia, that is 37° C (98.6° F), vs. standard care in which patients’ core temperature may decline to no further than 35.5° C (95.9° F).

Next on the list are a second POISE-3 comparison of BP-control strategies comparing hypotension avoidance vs. hypertension avoidance in patients undergoing noncardiac surgery; the pivotal CLASP 2 TR trial of patients with symptomatic tricuspid regurgitation on optimal medical therapy with vs. without treatment with the Edwards PASCAL Transcatheter Repair System; and one said to provide “insights from the Corevalve US Pivotal and SURTAVI trials” on 5-year incidence, timing, and predictors of hemodynamic valve deterioration transcatheter and surgical aortic bioprostheses.”

Rounding out the block of presentations: the ADAPT-TAVR comparison of the factor Xa inhibitor edoxaban (Lixiana) to dual-antiplatelet therapy for prevention of leaflet thrombosis after successful transcatheter aortic valve replacement (TAVR). The 235-patient trial was conducted at five centers in South Korea, Hong Kong, and Taiwan.
 

Monday, April 4, 11:00–12:15 p.m. LBCT V

This session includes the FLAVOUR randomized comparison of PCI guided by either FFR or intravascular ultrasound (IVUS) in 1,700 patients with 40%-70% stenoses. The patients from centers in China and South Korea were followed for death from any cause, MI, or any repeat revascularization at 24 months.

Also scheduled: the 2-year report on 4,000 patients with ST-segment elevation MI (STEMI) in the ACC-sponsored quality improvement program GHATI (Global Heart Attack Treatment Initiative); the GIPS-4 myocardial protection study of an estimated 380 patients with STEMI assigned to receive pre- and post-PCI infusions of sodium thiosulfate or placebo, with infarct size at 4 months as the primary endpoint; and a randomized test of an arrhythmia-monitoring implant for influence on clinical outcomes in 802 patients with a history of MI but no pacemaker or ICD indication, called BIO-GUARD-MI,

Last in the session: the Chocolate Touch Study of peripheral-artery angioplasty using a drug-coated balloon (DCB) with a confectionery name that treats lesions not with theobromine, but the antiproliferative mainstay paclitaxel.

The randomized comparison of the Chocolate Touch DCB (TriReme Medical) and the more established Lutonix DCB (Bard) assigned a projected 585 patients with symptomatic peripheral vascular disease to treatment of superficial femoral or popliteal artery lesions with one of the two paclitaxel-coated balloon catheters.
 

Monday, April 4, 12:45–2 p.m. Featured Clinical Research III. Room 143A 

The final session features five subgroup analyses or other updates from trials that have already reported their primary outcomes. Among them is the SPYRAL HTN-ON MED trial, which helped to revitalize hopes for renal denervation therapy as a catheter-based treatment for drug-resistant hypertension by showing significant effects on both systolic and diastolic blood pressure. The new data follow the trial’s more than 400 patients out to 3 years.

There is also a symptom and quality-of-life analysis from the 530-patient EMPULSE trial of 530 patients with stabilized acute HF assigned in-hospital to start on empagliflozin (Jardiance) or placebo. The trial made a splash last year when it reported a significant improvement in risk for death or HF rehospitalization for its patients put on the SGLT2 inhibitor.

A secondary analysis from CANTOS is also featured; the trial had randomly assigned more than 10,000 patients with recent acute MI and elevated C-reactive protein (CRP) levels to receive or not receive the anti-inflammatory canakinumab (Ilaris). Those assigned to active therapy showed benefits for a range of outcomes, including CV mortality and stroke, but no decreases in cholesterol levels. Billing for the new CANTOS analysis promises insights on the “differential impact of residual inflammatory risk and residual cholesterol risk among atherosclerosis patients with and without chronic kidney disease.”

The session also features “trends and final results” from the NACMI (North American COVID-19 Myocardial Infarction) registry, which had shown excellent primary-PCI results without compromise of door-to-balloon times in patients with confirmed SARS-CoV-2 infection; and a FIDELITY analysis of cardiorenal endpoints by history of CV disease in the study’s more than 13,000 patients with diabetes and CKD assigned to placebo or finerenone (Kerendia), a mineralocorticoid receptor antagonist.

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

Regardless of the pandemic’s sometimes mercurial behavior, the cardiology community appears set to reclaim valued traditions perhaps taken for granted in the pre-COVID era.

They include the bustling scientific congress and its myriad educational and networking prospects, along with pleiotropic effects like unplanned reunions with colleagues and catching up face-to-face with old friends.

That seems evident in the growing number of registrants for live attendance at at the annual scientific sessions of the American College of Cardiology, set for this Saturday through Monday in Washington as well as virtually, for a global reach that was unattainable in the pre-COVID era.

Registrations had hit the 11,000 mark and were picking up speed in recent weeks, ACC 2022 cochair Pamela B. Morris, MD, Medical University of South Carolina, Charleston, said at a mid-March presentation to the media.

They had reached about 12,880 and were still climbing a week before the conference, the ACC confirmed to this news organization. By then the professional registration had surpassed 9,900, of whom more than two-thirds reported plans to attend in person.

Dr. Morris said there had been 117 international submissions for what turned out to be 39 coveted spots on the meeting’s Late-Breaking Clinical Trial (LBCT) and Featured Clinical Research agenda spread across eight separate sessions.

On-site participants at the Walter E. Washington Convention Center should head for the Main Tent in Hall D for all LBCT presentations; venues for the Featured Clinical Research sessions are as noted below. Their real-time virtual equivalents will reside on the online platform’s Hot Topics channel. All noted session times are Eastern Daylight Time.
 

Saturday, April 2, 9:30 a.m.–10:30 a.m. Joint American College of Cardiology/Journal of the American College of Cardiology LBCT (I)

Leading off the conference’s first LBCT session, the randomized VALOR-HCM trial explored whether 16 weeks of mavacamten (MyoKardia) could help patients with severe obstructive hypertrophic cardiomyopathy (HCM) avoid septal reduction therapy, either surgical or by alcohol ablation.

The 22-center VALOR-HCM trial with an estimated enrollment of 100 follows EXPLORER-HCM, which in 2020 suggested the novel myosin-inhibiting agent could improve symptoms, exercise capacity, cardiac remodeling, and quality of life in such patients.

Simply advising people with heart failure (HF) to consume less salt is one thing, but it’s another to show them clinical trial evidence that it might help keep them out of the hospital. The SODIUM-HF (Study of Dietary Intervention Under 100 mmol in Heart Failure) study, conducted at 27 sites in six countries, sought to provide that evidence.

The trial randomly assigned 1,000 patients with NYHA class 2-3 HF to consume no more than 1,500 mg/day in sodium or to receive standard advice to limit sodium intake, and followed them for a year for the endpoint of death from any cause, cardiovascular (CV) hospitalization, or CV emergency department visit.

SODIUM-HF “may provide a rigorous evidence base for sodium restriction in patients with heart failure and may truly change our practice and how we recommend dietary modification,” ACC 2022 vice chair Douglas E. Drachman, MD, Massachusetts General Hospital, Boston, said at the media presentation.

In the same session, the CHAP (Chronic Hypertension and Pregnancy) study explored whether blood pressure (BP) control in pregnant women with new or untreated chronic hypertension could help avert preeclampsia, poor fetal outcomes, and other adverse events.

CHAP assigned about 2,400 women to receive either stepwise antihypertensive therapy to a BP goal of 140/90 mm Hg or lower or no such meds unless their BP reached or exceeded 160/105 mm Hg. Stepwise therapy featured either labetalol or extended-release nifedipine to start, the other agent added as necessary.

The LBCT block also includes the POISE-3 (Perioperative Ischemic Evaluation-3) comparison of the hemostatic agent tranexamic acid vs. placebo in nearly 10,000 patients undergoing noncardiac surgery. A separate randomization of the same cohort, to be reported at a Monday LBCT session, compared pre- and perioperative BP-control strategies.
 

Saturday, April 2, 12:00 p.m.–1:15 p.m. Featured Clinical Research I. Room 143A

This session features a subgroup analysis by age from the REVERSE-IT trial, which had previously showcased the monoclonal antibody bentracimab (PhaseBio Pharmaceuticals) for its ability to reverse the antiplatelet effects of ticagrelor.

REVERSE-IT is accompanied on the schedule by several secondary-endpoint presentations from trials whose primary outcomes have already been presented at meetings or in the journals.

They include the SCORED trial of sotagliflozin in patients with diabetes and chronic kidney disease (CKD); COMPLETE, which explored complete revascularization of multivessel coronary disease at primary stenting; and the FAME-3 comparison of coronary bypass surgery (CABG) vs. percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) readings.

The session is to conclude with EDIT-CMD, which was a small, randomized assessment of diltiazem for improving microvascular dysfunction in patients with chronic angina despite nonobstructive coronary disease.
 

Sunday, April 3, 8:00 a.m.–9:15 a.m. Joint American College of Cardiology/Journal of the American Medical Association LBCT (II)

The SuperWIN (Supermarket Web Intervention) study tested an innovative strategy for community-based promotion of healthy lifestyle choices: point-of-purchase dietary education for grocery shoppers with an online instructional component, and follow-up to determine whether it influenced future food choices.

“Dietary interventions are notoriously difficult for us to implement, let alone to study scientifically,” Dr. Drachman observed. “So we think that there may be opportunity for dietary interventions to be best implemented at grocery stores where people are doing their shopping for food.”

SuperWIN compared supermarket shoppers with at least one CV risk factor who participated in the education intervention to a nonintervention control group for any changes in their DASH scores. The scores reflected consistency with the venerable DASH diet based on participants’ food purchases over 3 months.

In the same session, the MITIGATE trial explored whether daily administration of icosapent ethyl (Vascepa) might cut the risk of upper respiratory infection (especially from SARS-CoV-2 or seasonal influenza virus) in persons 50 or older with a history of clinical coronary, neurovascular, or peripheral vascular disease or revascularization. The trial has an estimated enrollment of 39,600.

Accompanying SuperWIN and MITIGATE are studies of several dyslipidemia drugs, including the discontinued antisense agent vupanorsen (Pfizer), as tested in TRANSLATE-TIMI 70;  the PCSK9 inhibitor alirocumab (Praluent), explored for its effects on coronary plaque volume and composition in the PACMAN-AMI trial; and the APOLLO trial, a phase 1 evaluation of SLN360 (Silence Therapeutics), a short interfering ribonucleic acid (siRNA) that suppresses the molecular machinery in the liver that produces lipoprotein(a), or Lp(a).

The 32-patient APOLLO trial’s recently released top-line results suggested that SLN360 at varying dosages reduced Lp(a) levels by about one-half to more than 90%. Although elevated Lp(a) is known to track with CV risk, it remains to be shown whether dropping Lp(a) levels pharmacologically is protective.
 

Sunday, April 3, 9:45 a.m.–11:00 a.m. Joint American College of Cardiology/New England Journal of Medicine LBCT (III)

The meeting’s all-HF late-breaker session includes the METEORIC-HF trial, which compared the myotropic agent omecamtiv mecarbil (Cytokinetics) against placebo for effects on exercise performance over 20 weeks. The trial entered 276 patients with HF with reduced ejection fraction (HFrEF) and reduced peak VO₂.

The GALACTIC-HF trial had previously suggested that the drug improved the risk of HF-related events or CV death in more than 8000 patients with HFrEF, those with the lowest ejection fractions benefiting the most.

This block of trials also features DIAMOND, the latest trial with a gemologic name to look at the potassium sequestrant patiromer (Veltassa) for any protection against hyperkalemia, a familiar side effect of renin-angiotensin-aldosterone inhibitors. DIAMOND tested patiromer in 878 patients with HFrEF who were on beta-blockers and other HF-appropriate medications and had a history of drug-associated hyperkalemia.

Previously, the AMBER trial of patients with CKD or refractory hypertension on spironolactone had suggested the drug might be protective enough against hyperkalemia to allow higher and more consistent dosing of BP-lowering agents.

Also in the session: the randomized IVVE (Influenza Vaccine to Prevent Adverse Vascular Events) trial, with an estimated 5,000 patients with HF in Africa, Asia, and the Middle East; PROMPT-HF, with a projected 1,310 HF patients and billed as a cluster-randomized pragmatic trial of a strategy for improving guideline-directed outpatient medical therapy; and MAVA-LTE, the long-term extension study of an estimated 310 patients who were in the MAVERICK-HCM and EXPLORER-HCM mavacamten trials.
 

Sunday, April 3, 12:15–1:30 p.m. Featured Clinical Research II. Main Tent, Hall D

The arrhythmia-centric session includes PARTITA, with its estimated 590 patients with primary- or secondary-prevention implantable cardioverter-defibrillators (ICDs). The trial followed them initially for burden of untreated nonsustained ventricular tachycardia (VT) or events treated with anti-tachycardia pacing. Then it randomly assigned those who experienced a first appropriate ICD shock to either immediate VT ablation or standard care. The latter included ablation on next occurrence of arrhythmic storm.

Investigational oral factor XIa inhibitors, viewed by many as potentially safer as anticoagulants than contemporary oral inhibitors of factor Xa, are now on the scene and include milvexian (Bristol-Myers Squibb/Janssen) and, lately, asundexian (BAY 2433334; Bayer). The latter agent was compared to the factor Xa inhibitor apixaban (Eliquis) in 753 patients with AF in the phase 2 PACIFIC-AF trial, which looked at the newer drug’s safety and optimal dosing.

Also on the bill: a long-term follow-up of the mAFA-2 (Mobile AF Application 2) extension study, which explored the value of a smartphone-based atrial fibrillation (AF) screening app for improving risk of AF-related events; a presentation billed as “Residual Leaks Post Left Atrial Appendage Occlusion”; and one that declares “low rates of guideline-directed care” to be “associated with higher mortality” in patients with pacemakers or ICDs.
 

Monday, April 4, 8:30 a.m.–9:45 a.m. LBCT IV

This session is to open with the PROTECT trial, which sought to determine whether perioperative “aggressive warming” may be cardioprotective in patients with CV risk factors undergoing noncardiac surgery. Its estimated 5,100 patients were randomly assigned to a procedure that achieves normothermia, that is 37° C (98.6° F), vs. standard care in which patients’ core temperature may decline to no further than 35.5° C (95.9° F).

Next on the list are a second POISE-3 comparison of BP-control strategies comparing hypotension avoidance vs. hypertension avoidance in patients undergoing noncardiac surgery; the pivotal CLASP 2 TR trial of patients with symptomatic tricuspid regurgitation on optimal medical therapy with vs. without treatment with the Edwards PASCAL Transcatheter Repair System; and one said to provide “insights from the Corevalve US Pivotal and SURTAVI trials” on 5-year incidence, timing, and predictors of hemodynamic valve deterioration transcatheter and surgical aortic bioprostheses.”

Rounding out the block of presentations: the ADAPT-TAVR comparison of the factor Xa inhibitor edoxaban (Lixiana) to dual-antiplatelet therapy for prevention of leaflet thrombosis after successful transcatheter aortic valve replacement (TAVR). The 235-patient trial was conducted at five centers in South Korea, Hong Kong, and Taiwan.
 

Monday, April 4, 11:00–12:15 p.m. LBCT V

This session includes the FLAVOUR randomized comparison of PCI guided by either FFR or intravascular ultrasound (IVUS) in 1,700 patients with 40%-70% stenoses. The patients from centers in China and South Korea were followed for death from any cause, MI, or any repeat revascularization at 24 months.

Also scheduled: the 2-year report on 4,000 patients with ST-segment elevation MI (STEMI) in the ACC-sponsored quality improvement program GHATI (Global Heart Attack Treatment Initiative); the GIPS-4 myocardial protection study of an estimated 380 patients with STEMI assigned to receive pre- and post-PCI infusions of sodium thiosulfate or placebo, with infarct size at 4 months as the primary endpoint; and a randomized test of an arrhythmia-monitoring implant for influence on clinical outcomes in 802 patients with a history of MI but no pacemaker or ICD indication, called BIO-GUARD-MI,

Last in the session: the Chocolate Touch Study of peripheral-artery angioplasty using a drug-coated balloon (DCB) with a confectionery name that treats lesions not with theobromine, but the antiproliferative mainstay paclitaxel.

The randomized comparison of the Chocolate Touch DCB (TriReme Medical) and the more established Lutonix DCB (Bard) assigned a projected 585 patients with symptomatic peripheral vascular disease to treatment of superficial femoral or popliteal artery lesions with one of the two paclitaxel-coated balloon catheters.
 

Monday, April 4, 12:45–2 p.m. Featured Clinical Research III. Room 143A 

The final session features five subgroup analyses or other updates from trials that have already reported their primary outcomes. Among them is the SPYRAL HTN-ON MED trial, which helped to revitalize hopes for renal denervation therapy as a catheter-based treatment for drug-resistant hypertension by showing significant effects on both systolic and diastolic blood pressure. The new data follow the trial’s more than 400 patients out to 3 years.

There is also a symptom and quality-of-life analysis from the 530-patient EMPULSE trial of 530 patients with stabilized acute HF assigned in-hospital to start on empagliflozin (Jardiance) or placebo. The trial made a splash last year when it reported a significant improvement in risk for death or HF rehospitalization for its patients put on the SGLT2 inhibitor.

A secondary analysis from CANTOS is also featured; the trial had randomly assigned more than 10,000 patients with recent acute MI and elevated C-reactive protein (CRP) levels to receive or not receive the anti-inflammatory canakinumab (Ilaris). Those assigned to active therapy showed benefits for a range of outcomes, including CV mortality and stroke, but no decreases in cholesterol levels. Billing for the new CANTOS analysis promises insights on the “differential impact of residual inflammatory risk and residual cholesterol risk among atherosclerosis patients with and without chronic kidney disease.”

The session also features “trends and final results” from the NACMI (North American COVID-19 Myocardial Infarction) registry, which had shown excellent primary-PCI results without compromise of door-to-balloon times in patients with confirmed SARS-CoV-2 infection; and a FIDELITY analysis of cardiorenal endpoints by history of CV disease in the study’s more than 13,000 patients with diabetes and CKD assigned to placebo or finerenone (Kerendia), a mineralocorticoid receptor antagonist.

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

A controlled study of sleep-deprived young adults has provided the first causal evidence linking the lack of sleep to abdominal obesity and harmful visceral, or “belly” fat. In what the researchers claim is the first-ever study evaluating the relationship between sleep restriction and body fat distribution, they’ve reported the novel finding that the expansion of abdominal adipose tissue, and especially visceral fat, occurred as a function of shortened sleep.

Naima Covassin, PhD, a researcher in cardiovascular medicine at Mayo Clinic in Rochester, Minn., led the randomized, controlled study of 12 healthy, nonobese people randomized to controlled sleep restriction – 2 weeks of 4 hours of sleep a night – or controlled sleep of 9 hours a night, followed by a 3-day recovery period. The study was conducted in the hospital, monitored participants’ caloric intake, and used accelerometry to monitor energy expense. Participants ranged in age from 19 to 39 years.

“What we found was that at the end of 2 weeks these people put on just about a pound, 0.5 kg, of extra weight, which was significant but still very modest,” senior author Virend K. Somers, MD, PhD, said in an interview. “The average person who sleeps 4 hours a night thinks they’re doing OK if they only put on a pound.” Dr. Somers is the Alice Sheets Marriott Professor in Cardiovascular Medicine at Mayo Clinic.

“The problem is,” he said, “that when you do a more specific analysis you find that actually with the 1 pound the significant increase of the fat is in the belly area, particularly inside the belly.”

The study found that the patients on curtailed sleep ate on average an additional 308 calories a day more than their controlled sleep counterparts (95% confidence interval, 59.2-556.8 kcal/day; P = .015), and while that translated into a 0.5-kg weight gain (95% CI, 0.1-0.8 kg; P = .008), it also led to a 7.8-cm² increase visceral adipose tissue (VAT) (95% CI, 0.3-15.3 cm²; P = .042), representing an increase of around 11%. The study used CT on day 1 and day 18 (1 day after the 3-day recovery period) to evaluate the distribution of abdominal fat.

VAT findings post recovery

After the recovery period, however, the study found that VAT in the sleep-curtailed patients kept rising, yet body weight and subcutaneous fat dropped, and the increase in total abdominal fat flattened. “They slept a lot, they ate fewer calories and their weight came down, but, very importantly, their belly fat went up even further,” Dr. Somers said. On average, it increased another 3.125 cm² by day 21.

The findings raised a number of questions that need further exploration, Dr. Somers said. “There’s some biochemical message in the body that’s continuing to send fat to the visceral compartment,” he said. “What we don’t know is whether repetitive episodes of inadequate sleep actually accumulate over the years to give people a preponderance of belly fat.”

The study also showed that the traditional parameters used for evaluating cardiovascular risk are not enough, Dr. Somers said. “If we just did body weight, body mass index, and overall body fat percentage, we’d completely miss this,” he said.

Future investigations should focus on two points, he said: identifying the mechanisms that cause VAT accumulation with less sleep, and whether extending sleep can reverse the process.

“The big worry is obviously the heart,” Dr. Somers said. “Remember, these are not sick people. These are young healthy people who are doing the wrong thing with their body fat; they’re sending the fat to the completely wrong place.”

In an invited editorial, endocrinologist Harold Bays, MD, wrote that the study confirmed the need for evaluating sleep disorders as a potential cause of accumulated VAT. Dr. Bays of the University of Louisville (Ky.) is medical director and president of the Louisville Metabolic and Atherosclerosis Research Center.

“The biggest misconception of many clinicians, and some cardiologists, is that obesity is not a disease,” Dr. Bays said in an interview. “Even when some clinicians believe obesity is a disease, they believe its pathogenic potential is limited to visceral fat.” He noted that subcutaneous fat can lead to accumulation of VAT and epicardial fat, as well as fatty infiltration of the liver and other vital organs, resulting in increased epicardial adipose tissue and indirect adverse effects on the heart.

“Thus, even if disruption of sleep does not increase body weight, if disruption of sleep results in fat dysfunction – “sick fat” or adiposopathy – then this may result in increased CVD risk factors and unhealthy body composition, including an increase in visceral fat,” Dr. Bays said.

The study received funding from the National Institutes of Health. Dr. Somers disclosed relationships with Baker Tilly, Jazz Pharmaceuticals, Bayer, Sleep Number and Respicardia. Coauthors had no disclosures. Dr. Bays is medical director of Your Body Goal and chief science officer of the Obesity Medical Association.

A controlled study of sleep-deprived young adults has provided the first causal evidence linking the lack of sleep to abdominal obesity and harmful visceral, or “belly” fat. In what the researchers claim is the first-ever study evaluating the relationship between sleep restriction and body fat distribution, they’ve reported the novel finding that the expansion of abdominal adipose tissue, and especially visceral fat, occurred as a function of shortened sleep.

Naima Covassin, PhD, a researcher in cardiovascular medicine at Mayo Clinic in Rochester, Minn., led the randomized, controlled study of 12 healthy, nonobese people randomized to controlled sleep restriction – 2 weeks of 4 hours of sleep a night – or controlled sleep of 9 hours a night, followed by a 3-day recovery period. The study was conducted in the hospital, monitored participants’ caloric intake, and used accelerometry to monitor energy expense. Participants ranged in age from 19 to 39 years.

“What we found was that at the end of 2 weeks these people put on just about a pound, 0.5 kg, of extra weight, which was significant but still very modest,” senior author Virend K. Somers, MD, PhD, said in an interview. “The average person who sleeps 4 hours a night thinks they’re doing OK if they only put on a pound.” Dr. Somers is the Alice Sheets Marriott Professor in Cardiovascular Medicine at Mayo Clinic.

“The problem is,” he said, “that when you do a more specific analysis you find that actually with the 1 pound the significant increase of the fat is in the belly area, particularly inside the belly.”

The study found that the patients on curtailed sleep ate on average an additional 308 calories a day more than their controlled sleep counterparts (95% confidence interval, 59.2-556.8 kcal/day; P = .015), and while that translated into a 0.5-kg weight gain (95% CI, 0.1-0.8 kg; P = .008), it also led to a 7.8-cm² increase visceral adipose tissue (VAT) (95% CI, 0.3-15.3 cm²; P = .042), representing an increase of around 11%. The study used CT on day 1 and day 18 (1 day after the 3-day recovery period) to evaluate the distribution of abdominal fat.

VAT findings post recovery

After the recovery period, however, the study found that VAT in the sleep-curtailed patients kept rising, yet body weight and subcutaneous fat dropped, and the increase in total abdominal fat flattened. “They slept a lot, they ate fewer calories and their weight came down, but, very importantly, their belly fat went up even further,” Dr. Somers said. On average, it increased another 3.125 cm² by day 21.

The findings raised a number of questions that need further exploration, Dr. Somers said. “There’s some biochemical message in the body that’s continuing to send fat to the visceral compartment,” he said. “What we don’t know is whether repetitive episodes of inadequate sleep actually accumulate over the years to give people a preponderance of belly fat.”

The study also showed that the traditional parameters used for evaluating cardiovascular risk are not enough, Dr. Somers said. “If we just did body weight, body mass index, and overall body fat percentage, we’d completely miss this,” he said.

Future investigations should focus on two points, he said: identifying the mechanisms that cause VAT accumulation with less sleep, and whether extending sleep can reverse the process.

“The big worry is obviously the heart,” Dr. Somers said. “Remember, these are not sick people. These are young healthy people who are doing the wrong thing with their body fat; they’re sending the fat to the completely wrong place.”

In an invited editorial, endocrinologist Harold Bays, MD, wrote that the study confirmed the need for evaluating sleep disorders as a potential cause of accumulated VAT. Dr. Bays of the University of Louisville (Ky.) is medical director and president of the Louisville Metabolic and Atherosclerosis Research Center.

“The biggest misconception of many clinicians, and some cardiologists, is that obesity is not a disease,” Dr. Bays said in an interview. “Even when some clinicians believe obesity is a disease, they believe its pathogenic potential is limited to visceral fat.” He noted that subcutaneous fat can lead to accumulation of VAT and epicardial fat, as well as fatty infiltration of the liver and other vital organs, resulting in increased epicardial adipose tissue and indirect adverse effects on the heart.

“Thus, even if disruption of sleep does not increase body weight, if disruption of sleep results in fat dysfunction – “sick fat” or adiposopathy – then this may result in increased CVD risk factors and unhealthy body composition, including an increase in visceral fat,” Dr. Bays said.

The study received funding from the National Institutes of Health. Dr. Somers disclosed relationships with Baker Tilly, Jazz Pharmaceuticals, Bayer, Sleep Number and Respicardia. Coauthors had no disclosures. Dr. Bays is medical director of Your Body Goal and chief science officer of the Obesity Medical Association.

A controlled study of sleep-deprived young adults has provided the first causal evidence linking the lack of sleep to abdominal obesity and harmful visceral, or “belly” fat. In what the researchers claim is the first-ever study evaluating the relationship between sleep restriction and body fat distribution, they’ve reported the novel finding that the expansion of abdominal adipose tissue, and especially visceral fat, occurred as a function of shortened sleep.

Naima Covassin, PhD, a researcher in cardiovascular medicine at Mayo Clinic in Rochester, Minn., led the randomized, controlled study of 12 healthy, nonobese people randomized to controlled sleep restriction – 2 weeks of 4 hours of sleep a night – or controlled sleep of 9 hours a night, followed by a 3-day recovery period. The study was conducted in the hospital, monitored participants’ caloric intake, and used accelerometry to monitor energy expense. Participants ranged in age from 19 to 39 years.

“What we found was that at the end of 2 weeks these people put on just about a pound, 0.5 kg, of extra weight, which was significant but still very modest,” senior author Virend K. Somers, MD, PhD, said in an interview. “The average person who sleeps 4 hours a night thinks they’re doing OK if they only put on a pound.” Dr. Somers is the Alice Sheets Marriott Professor in Cardiovascular Medicine at Mayo Clinic.

“The problem is,” he said, “that when you do a more specific analysis you find that actually with the 1 pound the significant increase of the fat is in the belly area, particularly inside the belly.”

The study found that the patients on curtailed sleep ate on average an additional 308 calories a day more than their controlled sleep counterparts (95% confidence interval, 59.2-556.8 kcal/day; P = .015), and while that translated into a 0.5-kg weight gain (95% CI, 0.1-0.8 kg; P = .008), it also led to a 7.8-cm² increase visceral adipose tissue (VAT) (95% CI, 0.3-15.3 cm²; P = .042), representing an increase of around 11%. The study used CT on day 1 and day 18 (1 day after the 3-day recovery period) to evaluate the distribution of abdominal fat.

VAT findings post recovery

After the recovery period, however, the study found that VAT in the sleep-curtailed patients kept rising, yet body weight and subcutaneous fat dropped, and the increase in total abdominal fat flattened. “They slept a lot, they ate fewer calories and their weight came down, but, very importantly, their belly fat went up even further,” Dr. Somers said. On average, it increased another 3.125 cm² by day 21.

The findings raised a number of questions that need further exploration, Dr. Somers said. “There’s some biochemical message in the body that’s continuing to send fat to the visceral compartment,” he said. “What we don’t know is whether repetitive episodes of inadequate sleep actually accumulate over the years to give people a preponderance of belly fat.”

The study also showed that the traditional parameters used for evaluating cardiovascular risk are not enough, Dr. Somers said. “If we just did body weight, body mass index, and overall body fat percentage, we’d completely miss this,” he said.

Future investigations should focus on two points, he said: identifying the mechanisms that cause VAT accumulation with less sleep, and whether extending sleep can reverse the process.

“The big worry is obviously the heart,” Dr. Somers said. “Remember, these are not sick people. These are young healthy people who are doing the wrong thing with their body fat; they’re sending the fat to the completely wrong place.”

In an invited editorial, endocrinologist Harold Bays, MD, wrote that the study confirmed the need for evaluating sleep disorders as a potential cause of accumulated VAT. Dr. Bays of the University of Louisville (Ky.) is medical director and president of the Louisville Metabolic and Atherosclerosis Research Center.

“The biggest misconception of many clinicians, and some cardiologists, is that obesity is not a disease,” Dr. Bays said in an interview. “Even when some clinicians believe obesity is a disease, they believe its pathogenic potential is limited to visceral fat.” He noted that subcutaneous fat can lead to accumulation of VAT and epicardial fat, as well as fatty infiltration of the liver and other vital organs, resulting in increased epicardial adipose tissue and indirect adverse effects on the heart.

“Thus, even if disruption of sleep does not increase body weight, if disruption of sleep results in fat dysfunction – “sick fat” or adiposopathy – then this may result in increased CVD risk factors and unhealthy body composition, including an increase in visceral fat,” Dr. Bays said.

The study received funding from the National Institutes of Health. Dr. Somers disclosed relationships with Baker Tilly, Jazz Pharmaceuticals, Bayer, Sleep Number and Respicardia. Coauthors had no disclosures. Dr. Bays is medical director of Your Body Goal and chief science officer of the Obesity Medical Association.

A trio of analyses based on the prospective UK Biobank cohort suggest that regular coffee drinking, especially a daily intake of two to three cups, is not only safe for the heart but may be cardioprotective.

People without cardiovascular disease with that level of coffee intake, compared with those who weren’t coffee drinkers, showed significantly reduced risks of death and a range of CVD endpoints, the reductions ranging from 8% to 15% over about 10 years.

S_Bachstroem/Getty Images

In a separate analysis, participants with CVD at baseline also showed significantly improved survival with coffee intake of two to three cups daily, and no increased risk of arrhythmias.

In a third cut of the UK Biobank data, the clinical benefits of the same level of coffee drinking were observed whether the coffee consumed was the “instant” kind for reconstitution with water or brewed from ground whole beans.

Some clinicians advise their patients that coffee drinking may trigger or worsen some types of heart disease, observed Peter M. Kistler, MD, the Alfred Hospital and Baker Heart and Diabetes Institute, Melbourne. But the current analyses suggest that “daily coffee intake should not be discouraged, but rather considered part of a healthy diet.”

Dr. Kistler and colleagues are slated to present the three UK Biobank cohort analyses separately at the annual scientific sessions of the American College of Cardiology. He presented some of the data and commented on them at a press conference held in advance of the meeting.

UK Biobank study participants, who were on average in their late 50s, reported their level of daily coffee intake and preferred type of coffee on questionnaires. The researchers observed generally U-shaped relationships between daily number of cups of coffee and incident CVD, heart failure, coronary heart disease (CHD), stroke, atrial fibrillation, any arrhythmia, and death over 10 years.

“This is music to I think many of our patients’ ears, as well as many in the field of cardiology, as those of us that wake up early and stay up late in the hospital consume a fair amount of coffee,” observed Katie Berlacher, MD, associate chief of cardiology education at the University of Pittsburgh Medical Center.

The analyses were based on a large cohort and saw a consistent pattern for several cardiovascular outcomes, observed Dr. Berlacher, incoming ACC scientific session vice chair.

The findings could have a “profound impact in daily clinical care, as many of us caution patients who have or are at risk for having CV[D] against coffee consumption,” she told this news organization by email.

“These studies suggest that we do not have objective evidence to caution nor ask patients to stop drinking coffee, including patients who have arrhythmias.”

But importantly, “these studies are not causal,” she added. “So we cannot go so far as to recommend coffee consumption, though one could posit that randomized prospective studies should be done to elucidate causation.”

Coffee, Dr. Kistler observed, “is the most common cognitive enhancer. It wakes you up, makes you mentally sharper, and it’s a very important component of many people’s daily lives. The take-home message is that clinicians should NOT advise patients to stop drinking coffee up to three cups per day.”

Also, “in non–coffee drinkers, we do not have the data to suggest they should start drinking coffee,” he said. Moreover, people shouldn’t necessarily increase their coffee intake, particularly if it makes them feel anxious or uncomfortable.
 

Benefits with or without known heart disease

The researchers identified 382,535 participants in the UK Biobank cohort who were free of CVD at baseline. Their median age was 57, and 52% were women.

Those who reported regular daily intake of two to three cups of coffee, compared with those who were not coffee drinkers, showed significantly reduced risks of CVD (hazard ratio, 0.91; 95% confidence interval, 0.88-0.94), CHD (HR, 0.90; 95% CI, 0.87-0.93), heart failure (HR, 0.85; 95% CI, 0.81-0.90), arrhythmias (HR, 0.92; 95% CI, 0.88-0.95), and death from any cause over 10 years (HR, 0.86; 95% CI, 0.83-0.90) (P < .01 for all endpoints).

The risk of CVD death hit its lowest point at an intake of one cup per day (HR, 0.83; 95% CI, 0.75-0.93). The risk of stroke was lowest at less than one cup per day (HR, 0.85; 95% CI, 0.75-0.96).

A separate analysis found similar outcomes among a different subset of UK Biobank participants with recognized CVD at baseline. Among 34,279 such persons, those who drank two to three cups of coffee per day, compared with non–coffee drinkers, showed a reduced risk of death over 10 years (HR, 0.92; 95% CI, 0.86-0.99; P = .03).

Among the 24,111 persons diagnosed with arrhythmias at baseline, the lowest mortality risk was observed at one cup per day (HR, 0.85; 95% CI, 0.78-0.94; P < .01). Among those with atrial fibrillation or atrial flutter, one cup per day was associated with a mortality HR of 0.82 (95% CI, 0.73-0.93; P < .01).

In still another analysis of UK Biobank cohort, incident CVD and mortality during the 10-year follow-up was similarly reduced among participants who reported consumption of brewed ground coffee and, separately, instant coffee, compared with non–coffee drinkers. Decaffeinated coffee showed a mostly neutral or inconsistent effect on the clinical endpoints.

The lowest CVD risk was observed at two to three cups per day among those regularly drinking ground coffee (HR, 0.83; 95% CI, 0.79-0.87) and those predominantly taking instant coffee (HR, 0.91; 95% CI, 0.88-0.95).

Potential mechanisms, study limitations

“Caffeine blocks adenosine receptors, which may explain its potential mild antiarrhythmic properties,” Dr. Kistler said. “Regular coffee drinkers with supraventricular tachycardia coming to the emergency department often need higher adenosine doses to revert.”

Caffeine has a role in weight loss through inhibition of gut fatty acid absorption and increase in basal metabolic rate, Dr. Kistler added, and coffee has been associated with a significantly reduced risk of new-onset type 2 diabetes.

However, coffee beans contain more than 100 biologically active compounds, he noted. They include antioxidant polyphenols that reduce oxidative stress and modulate metabolism. Better survival with habitual coffee consumption may be related to improved endothelial function, circulating antioxidants, improved insulin sensitivity, or reduced inflammation, the researchers noted.

They acknowledged some limitations to the analyses. Cause and effect can’t be determined from the observational data. Also, a cup of coffee in the United Kingdom means about 200-250 mL of brew, but its actual caffeine content can vary from 90 mg to 250 mg. Also, data regarding added sugar or milk was lacking. And UK Biobank participants are predominantly White, so the findings may not be generalizable to other populations.

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

A trio of analyses based on the prospective UK Biobank cohort suggest that regular coffee drinking, especially a daily intake of two to three cups, is not only safe for the heart but may be cardioprotective.

People without cardiovascular disease with that level of coffee intake, compared with those who weren’t coffee drinkers, showed significantly reduced risks of death and a range of CVD endpoints, the reductions ranging from 8% to 15% over about 10 years.

S_Bachstroem/Getty Images

In a separate analysis, participants with CVD at baseline also showed significantly improved survival with coffee intake of two to three cups daily, and no increased risk of arrhythmias.

In a third cut of the UK Biobank data, the clinical benefits of the same level of coffee drinking were observed whether the coffee consumed was the “instant” kind for reconstitution with water or brewed from ground whole beans.

Some clinicians advise their patients that coffee drinking may trigger or worsen some types of heart disease, observed Peter M. Kistler, MD, the Alfred Hospital and Baker Heart and Diabetes Institute, Melbourne. But the current analyses suggest that “daily coffee intake should not be discouraged, but rather considered part of a healthy diet.”

Dr. Kistler and colleagues are slated to present the three UK Biobank cohort analyses separately at the annual scientific sessions of the American College of Cardiology. He presented some of the data and commented on them at a press conference held in advance of the meeting.

UK Biobank study participants, who were on average in their late 50s, reported their level of daily coffee intake and preferred type of coffee on questionnaires. The researchers observed generally U-shaped relationships between daily number of cups of coffee and incident CVD, heart failure, coronary heart disease (CHD), stroke, atrial fibrillation, any arrhythmia, and death over 10 years.

“This is music to I think many of our patients’ ears, as well as many in the field of cardiology, as those of us that wake up early and stay up late in the hospital consume a fair amount of coffee,” observed Katie Berlacher, MD, associate chief of cardiology education at the University of Pittsburgh Medical Center.

The analyses were based on a large cohort and saw a consistent pattern for several cardiovascular outcomes, observed Dr. Berlacher, incoming ACC scientific session vice chair.

The findings could have a “profound impact in daily clinical care, as many of us caution patients who have or are at risk for having CV[D] against coffee consumption,” she told this news organization by email.

“These studies suggest that we do not have objective evidence to caution nor ask patients to stop drinking coffee, including patients who have arrhythmias.”

But importantly, “these studies are not causal,” she added. “So we cannot go so far as to recommend coffee consumption, though one could posit that randomized prospective studies should be done to elucidate causation.”

Coffee, Dr. Kistler observed, “is the most common cognitive enhancer. It wakes you up, makes you mentally sharper, and it’s a very important component of many people’s daily lives. The take-home message is that clinicians should NOT advise patients to stop drinking coffee up to three cups per day.”

Also, “in non–coffee drinkers, we do not have the data to suggest they should start drinking coffee,” he said. Moreover, people shouldn’t necessarily increase their coffee intake, particularly if it makes them feel anxious or uncomfortable.
 

Benefits with or without known heart disease

The researchers identified 382,535 participants in the UK Biobank cohort who were free of CVD at baseline. Their median age was 57, and 52% were women.

Those who reported regular daily intake of two to three cups of coffee, compared with those who were not coffee drinkers, showed significantly reduced risks of CVD (hazard ratio, 0.91; 95% confidence interval, 0.88-0.94), CHD (HR, 0.90; 95% CI, 0.87-0.93), heart failure (HR, 0.85; 95% CI, 0.81-0.90), arrhythmias (HR, 0.92; 95% CI, 0.88-0.95), and death from any cause over 10 years (HR, 0.86; 95% CI, 0.83-0.90) (P < .01 for all endpoints).

The risk of CVD death hit its lowest point at an intake of one cup per day (HR, 0.83; 95% CI, 0.75-0.93). The risk of stroke was lowest at less than one cup per day (HR, 0.85; 95% CI, 0.75-0.96).

A separate analysis found similar outcomes among a different subset of UK Biobank participants with recognized CVD at baseline. Among 34,279 such persons, those who drank two to three cups of coffee per day, compared with non–coffee drinkers, showed a reduced risk of death over 10 years (HR, 0.92; 95% CI, 0.86-0.99; P = .03).

Among the 24,111 persons diagnosed with arrhythmias at baseline, the lowest mortality risk was observed at one cup per day (HR, 0.85; 95% CI, 0.78-0.94; P < .01). Among those with atrial fibrillation or atrial flutter, one cup per day was associated with a mortality HR of 0.82 (95% CI, 0.73-0.93; P < .01).

In still another analysis of UK Biobank cohort, incident CVD and mortality during the 10-year follow-up was similarly reduced among participants who reported consumption of brewed ground coffee and, separately, instant coffee, compared with non–coffee drinkers. Decaffeinated coffee showed a mostly neutral or inconsistent effect on the clinical endpoints.

The lowest CVD risk was observed at two to three cups per day among those regularly drinking ground coffee (HR, 0.83; 95% CI, 0.79-0.87) and those predominantly taking instant coffee (HR, 0.91; 95% CI, 0.88-0.95).

Potential mechanisms, study limitations

“Caffeine blocks adenosine receptors, which may explain its potential mild antiarrhythmic properties,” Dr. Kistler said. “Regular coffee drinkers with supraventricular tachycardia coming to the emergency department often need higher adenosine doses to revert.”

Caffeine has a role in weight loss through inhibition of gut fatty acid absorption and increase in basal metabolic rate, Dr. Kistler added, and coffee has been associated with a significantly reduced risk of new-onset type 2 diabetes.

However, coffee beans contain more than 100 biologically active compounds, he noted. They include antioxidant polyphenols that reduce oxidative stress and modulate metabolism. Better survival with habitual coffee consumption may be related to improved endothelial function, circulating antioxidants, improved insulin sensitivity, or reduced inflammation, the researchers noted.

They acknowledged some limitations to the analyses. Cause and effect can’t be determined from the observational data. Also, a cup of coffee in the United Kingdom means about 200-250 mL of brew, but its actual caffeine content can vary from 90 mg to 250 mg. Also, data regarding added sugar or milk was lacking. And UK Biobank participants are predominantly White, so the findings may not be generalizable to other populations.

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

A trio of analyses based on the prospective UK Biobank cohort suggest that regular coffee drinking, especially a daily intake of two to three cups, is not only safe for the heart but may be cardioprotective.

People without cardiovascular disease with that level of coffee intake, compared with those who weren’t coffee drinkers, showed significantly reduced risks of death and a range of CVD endpoints, the reductions ranging from 8% to 15% over about 10 years.

S_Bachstroem/Getty Images

In a separate analysis, participants with CVD at baseline also showed significantly improved survival with coffee intake of two to three cups daily, and no increased risk of arrhythmias.

In a third cut of the UK Biobank data, the clinical benefits of the same level of coffee drinking were observed whether the coffee consumed was the “instant” kind for reconstitution with water or brewed from ground whole beans.

Some clinicians advise their patients that coffee drinking may trigger or worsen some types of heart disease, observed Peter M. Kistler, MD, the Alfred Hospital and Baker Heart and Diabetes Institute, Melbourne. But the current analyses suggest that “daily coffee intake should not be discouraged, but rather considered part of a healthy diet.”

Dr. Kistler and colleagues are slated to present the three UK Biobank cohort analyses separately at the annual scientific sessions of the American College of Cardiology. He presented some of the data and commented on them at a press conference held in advance of the meeting.

UK Biobank study participants, who were on average in their late 50s, reported their level of daily coffee intake and preferred type of coffee on questionnaires. The researchers observed generally U-shaped relationships between daily number of cups of coffee and incident CVD, heart failure, coronary heart disease (CHD), stroke, atrial fibrillation, any arrhythmia, and death over 10 years.

“This is music to I think many of our patients’ ears, as well as many in the field of cardiology, as those of us that wake up early and stay up late in the hospital consume a fair amount of coffee,” observed Katie Berlacher, MD, associate chief of cardiology education at the University of Pittsburgh Medical Center.

The analyses were based on a large cohort and saw a consistent pattern for several cardiovascular outcomes, observed Dr. Berlacher, incoming ACC scientific session vice chair.

The findings could have a “profound impact in daily clinical care, as many of us caution patients who have or are at risk for having CV[D] against coffee consumption,” she told this news organization by email.

“These studies suggest that we do not have objective evidence to caution nor ask patients to stop drinking coffee, including patients who have arrhythmias.”

But importantly, “these studies are not causal,” she added. “So we cannot go so far as to recommend coffee consumption, though one could posit that randomized prospective studies should be done to elucidate causation.”

Coffee, Dr. Kistler observed, “is the most common cognitive enhancer. It wakes you up, makes you mentally sharper, and it’s a very important component of many people’s daily lives. The take-home message is that clinicians should NOT advise patients to stop drinking coffee up to three cups per day.”

Also, “in non–coffee drinkers, we do not have the data to suggest they should start drinking coffee,” he said. Moreover, people shouldn’t necessarily increase their coffee intake, particularly if it makes them feel anxious or uncomfortable.
 

Benefits with or without known heart disease

The researchers identified 382,535 participants in the UK Biobank cohort who were free of CVD at baseline. Their median age was 57, and 52% were women.

Those who reported regular daily intake of two to three cups of coffee, compared with those who were not coffee drinkers, showed significantly reduced risks of CVD (hazard ratio, 0.91; 95% confidence interval, 0.88-0.94), CHD (HR, 0.90; 95% CI, 0.87-0.93), heart failure (HR, 0.85; 95% CI, 0.81-0.90), arrhythmias (HR, 0.92; 95% CI, 0.88-0.95), and death from any cause over 10 years (HR, 0.86; 95% CI, 0.83-0.90) (P < .01 for all endpoints).

The risk of CVD death hit its lowest point at an intake of one cup per day (HR, 0.83; 95% CI, 0.75-0.93). The risk of stroke was lowest at less than one cup per day (HR, 0.85; 95% CI, 0.75-0.96).

A separate analysis found similar outcomes among a different subset of UK Biobank participants with recognized CVD at baseline. Among 34,279 such persons, those who drank two to three cups of coffee per day, compared with non–coffee drinkers, showed a reduced risk of death over 10 years (HR, 0.92; 95% CI, 0.86-0.99; P = .03).

Among the 24,111 persons diagnosed with arrhythmias at baseline, the lowest mortality risk was observed at one cup per day (HR, 0.85; 95% CI, 0.78-0.94; P < .01). Among those with atrial fibrillation or atrial flutter, one cup per day was associated with a mortality HR of 0.82 (95% CI, 0.73-0.93; P < .01).

In still another analysis of UK Biobank cohort, incident CVD and mortality during the 10-year follow-up was similarly reduced among participants who reported consumption of brewed ground coffee and, separately, instant coffee, compared with non–coffee drinkers. Decaffeinated coffee showed a mostly neutral or inconsistent effect on the clinical endpoints.

The lowest CVD risk was observed at two to three cups per day among those regularly drinking ground coffee (HR, 0.83; 95% CI, 0.79-0.87) and those predominantly taking instant coffee (HR, 0.91; 95% CI, 0.88-0.95).

Potential mechanisms, study limitations

“Caffeine blocks adenosine receptors, which may explain its potential mild antiarrhythmic properties,” Dr. Kistler said. “Regular coffee drinkers with supraventricular tachycardia coming to the emergency department often need higher adenosine doses to revert.”

Caffeine has a role in weight loss through inhibition of gut fatty acid absorption and increase in basal metabolic rate, Dr. Kistler added, and coffee has been associated with a significantly reduced risk of new-onset type 2 diabetes.

However, coffee beans contain more than 100 biologically active compounds, he noted. They include antioxidant polyphenols that reduce oxidative stress and modulate metabolism. Better survival with habitual coffee consumption may be related to improved endothelial function, circulating antioxidants, improved insulin sensitivity, or reduced inflammation, the researchers noted.

They acknowledged some limitations to the analyses. Cause and effect can’t be determined from the observational data. Also, a cup of coffee in the United Kingdom means about 200-250 mL of brew, but its actual caffeine content can vary from 90 mg to 250 mg. Also, data regarding added sugar or milk was lacking. And UK Biobank participants are predominantly White, so the findings may not be generalizable to other populations.

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

Five international cardiac surgery associations have banded together to address “substantive concerns” regarding the recently updated Valve Academic Research Consortium 3 (VARC-3) clinical endpoint definitions for aortic valve research.

The VARC-3 update was a multidisciplinary effort that included more than a dozen new or modified definitions for use in transcatheter and surgical aortic valve replacement (TAVR/SAVR) clinical trials, but drew criticism last year from surgeons that some of its definitions favor TAVR over surgery and that its writing committee had deep ties to industry and lacked diversity.

The new surgical associations’ position statement calls out five specific VARC-3 definitions – rehospitalization, valve thrombosis, bleeding, myocardial infarction (MI), and left bundle-branch block (LBBB).

The statement was jointly issued by the Society of Thoracic Surgeons (STS), the American Association for Thoracic Surgery, the European Association for Cardio-Thoracic Surgery, the Asian Society for Cardiovascular and Thoracic Surgery, and the Latin American Association of Cardiac and Endovascular Surgery.

It was copublished in Annals of Thoracic Surgery, the Journal of Thoracic and Cardiovascular Surgery, the European Journal of Cardio-Thoracic Surgery, and the Asian Cardiovascular and Thoracic Annals.

“We hope that this message can be seen, even if it’s somewhat difficult to hear sometimes, as positive constructive criticism compared to some of the dialogue that we’ve had on social media,” lead author Patrick O. Myers, MD, Lausanne (Switzerland) University Hospital, said in an interview. “It’s not criticizing people or the process but just trying to make these definitions better to ensure the good design of clinical trials.”

The president of each surgical association recommended representatives to help write the position statement, and once completed over Zoom meetings, it received formal endorsement from each association prior to publication, he said.

Reached for comment, VARC-3 lead author Philippe Généreux, MD, Gagnon Cardiovascular Institute, Morristown (N.J.) Medical Center, said, “I was pleasantly surprised that their comments were actually pretty minor and that most of these comments are really more a reflection, not of the validity of the definitions, but rather their applications.”

He noted that all the potential issues with the definitions were already discussed during the making of VARC-3 and resolved by consensus of more than 50 experts including the STS president at the time, Food and Drug Administration officials, and experts from the community.

“To be quite honest, I’m not sure they have consensus,” Dr. Généreux said. He added that the writing committee welcomes input from anyone, but “we’re not going to change the definitions to please eight individuals if we strongly believe by consensus of experts in the field that this is not the right thing to do.”

Rehospitalizations and valve thrombosis

The surgical associations praise VARC-3 for providing a standardized definition of bioprosthetic valve failure, but say they will not endorse the inclusion of rehospitalization as a component of the primary efficacy composite endpoint along with all-cause mortality, stroke, and quality of life.

They note that rehospitalizations outnumber mortality events, especially in short follow-up trials, and that the superiority of TAVR at 1 year in the PARTNER 3 trial of low-risk patients was driven primarily by more rehospitalizations in the surgical arm, but that this superiority was waning at 2 years of follow-up.

“The first thing we are calling for is that it shouldn’t be part of the primary composite outcome measure,” Dr. Myers said. But if it really has to be included, a 30-day blanking period for rehospitalization “would acknowledge that there’s a greater risk of rehospitalization during the acute phase of recovering from surgery.”

Dr. Généreux said that VARC-3 provides granular details for defining the different types of hospitalizations, but that a 30-day blanking period makes no sense. “If you close your eyes to anything within 30 days because you don’t like it, you’re missing the opportunity to improve your procedure, to improve your treatment, and to characterize precisely what happened with your patient.”

The new document lauds VARC-3’s focus on patient-centered and clinically relevant endpoints but questions the definition of valve thrombosis as a “clinically significant” thrombus. It points out that the incidence of valve thrombosis was significantly higher with TAVR versus SAVR in PARTNER 3 using the older VARC-2 definition, which did not require evidence of clinical sequelae (2.6% vs. 0.7%; P = .02). Under the new definition, however, half of the thrombi would be relabeled as “nothing there,” Dr. Myers said.

“As we’re doing this in younger and younger patients who will survive longer, there is a question of thrombus having an effect on the valve and leading to earlier structural valve deterioration,” he added. “All this is conjecture. We don’t have the data. So mainly what we’re advocating is that all thrombi should be reported.”
 

MIs, bleeding, and LBBB

The policy statement also criticizes VARC-3’s decision to define periprocedural (type 5) MI using a biomarker-only definition without need of clinical confirmation. Such definitions have been shown to have a very poor prognostic significance in surgical series compared with the Universal Definitions of Myocardial Infarction, Dr. Myers said.

“What’s interesting is that for thrombus and bleeding, they require clinical correlation, but on the perioperative MI they now use a definition that does not require clinical significance, meaning no ECG changes, no regional wall motion abnormalities or things like that,” he observed.

The decision also seems to disregard the EXCEL trial controversy that illustrated how outcomes and a trial’s message can change depending on which definition of periprocedural MI is used.

With regard to bleeding, the surgical associations agree with the VARC-3 recommendation to use different thresholds when bleeding is integrated into a composite endpoint (type 2 or greater for TAVR and types 3 or greater for SAVR) but suggest this important point should be featured in the chapter on bleeding rather than the section on composite endpoints.

The surgical associations say VARC-3 also got it right adding the need for a new permanent pacemaker to the early composite safety endpoint, but that it was a “missed opportunity” not to include new left bundle-branch block in the safety composite, despite recognizing that this may become an important endpoint to consider in the future.

Dr. Myers said that left bundle-branch block could have implications for survival as TAVR moves into lower-risk, younger patients, as some data with 1-year follow-up suggest it has a prognostic impact, even in the higher-risk older patients with more competing risks.

Finally, the surgical associations point out that only two of the 23 VARC-3 authors were practicing cardiac surgeons and say that a more diverse writing group “may help mitigate issues related to the duality of interests.”

Dr. Généreux said that the final author list is not a reflection of the rigorous work done by 11 cardiac surgeons including the two surgeon authors. The VARC-3 writing committee also had a good representation of women, unlike the surgical position statement, which was penned by eight men.

Dr. Myers reported no relevant financial relationships. Coauthors disclosed ties with EACTS, Edwards Lifesciences, Medtronic, Abbott Vascular, Boston Scientific, CryoLife, Shockwave, and JenaValve. Dr. Généreux disclosed ties with Abbott Vascular, Abiomed, Boston Scientific, Cardinal Health, Cardiovascular Systems, Edwards Lifesciences, Medtronic, Opsens, Siemens, SoundBite Medical Solutions, Sig.Num, Saranas, Teleflex, Tryton Medical, Pi-Cardia, and Puzzle Medical.

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

Five international cardiac surgery associations have banded together to address “substantive concerns” regarding the recently updated Valve Academic Research Consortium 3 (VARC-3) clinical endpoint definitions for aortic valve research.

The VARC-3 update was a multidisciplinary effort that included more than a dozen new or modified definitions for use in transcatheter and surgical aortic valve replacement (TAVR/SAVR) clinical trials, but drew criticism last year from surgeons that some of its definitions favor TAVR over surgery and that its writing committee had deep ties to industry and lacked diversity.

The new surgical associations’ position statement calls out five specific VARC-3 definitions – rehospitalization, valve thrombosis, bleeding, myocardial infarction (MI), and left bundle-branch block (LBBB).

The statement was jointly issued by the Society of Thoracic Surgeons (STS), the American Association for Thoracic Surgery, the European Association for Cardio-Thoracic Surgery, the Asian Society for Cardiovascular and Thoracic Surgery, and the Latin American Association of Cardiac and Endovascular Surgery.

It was copublished in Annals of Thoracic Surgery, the Journal of Thoracic and Cardiovascular Surgery, the European Journal of Cardio-Thoracic Surgery, and the Asian Cardiovascular and Thoracic Annals.

“We hope that this message can be seen, even if it’s somewhat difficult to hear sometimes, as positive constructive criticism compared to some of the dialogue that we’ve had on social media,” lead author Patrick O. Myers, MD, Lausanne (Switzerland) University Hospital, said in an interview. “It’s not criticizing people or the process but just trying to make these definitions better to ensure the good design of clinical trials.”

The president of each surgical association recommended representatives to help write the position statement, and once completed over Zoom meetings, it received formal endorsement from each association prior to publication, he said.

Reached for comment, VARC-3 lead author Philippe Généreux, MD, Gagnon Cardiovascular Institute, Morristown (N.J.) Medical Center, said, “I was pleasantly surprised that their comments were actually pretty minor and that most of these comments are really more a reflection, not of the validity of the definitions, but rather their applications.”

He noted that all the potential issues with the definitions were already discussed during the making of VARC-3 and resolved by consensus of more than 50 experts including the STS president at the time, Food and Drug Administration officials, and experts from the community.

“To be quite honest, I’m not sure they have consensus,” Dr. Généreux said. He added that the writing committee welcomes input from anyone, but “we’re not going to change the definitions to please eight individuals if we strongly believe by consensus of experts in the field that this is not the right thing to do.”

Rehospitalizations and valve thrombosis

The surgical associations praise VARC-3 for providing a standardized definition of bioprosthetic valve failure, but say they will not endorse the inclusion of rehospitalization as a component of the primary efficacy composite endpoint along with all-cause mortality, stroke, and quality of life.

They note that rehospitalizations outnumber mortality events, especially in short follow-up trials, and that the superiority of TAVR at 1 year in the PARTNER 3 trial of low-risk patients was driven primarily by more rehospitalizations in the surgical arm, but that this superiority was waning at 2 years of follow-up.

“The first thing we are calling for is that it shouldn’t be part of the primary composite outcome measure,” Dr. Myers said. But if it really has to be included, a 30-day blanking period for rehospitalization “would acknowledge that there’s a greater risk of rehospitalization during the acute phase of recovering from surgery.”

Dr. Généreux said that VARC-3 provides granular details for defining the different types of hospitalizations, but that a 30-day blanking period makes no sense. “If you close your eyes to anything within 30 days because you don’t like it, you’re missing the opportunity to improve your procedure, to improve your treatment, and to characterize precisely what happened with your patient.”

The new document lauds VARC-3’s focus on patient-centered and clinically relevant endpoints but questions the definition of valve thrombosis as a “clinically significant” thrombus. It points out that the incidence of valve thrombosis was significantly higher with TAVR versus SAVR in PARTNER 3 using the older VARC-2 definition, which did not require evidence of clinical sequelae (2.6% vs. 0.7%; P = .02). Under the new definition, however, half of the thrombi would be relabeled as “nothing there,” Dr. Myers said.

“As we’re doing this in younger and younger patients who will survive longer, there is a question of thrombus having an effect on the valve and leading to earlier structural valve deterioration,” he added. “All this is conjecture. We don’t have the data. So mainly what we’re advocating is that all thrombi should be reported.”
 

MIs, bleeding, and LBBB

The policy statement also criticizes VARC-3’s decision to define periprocedural (type 5) MI using a biomarker-only definition without need of clinical confirmation. Such definitions have been shown to have a very poor prognostic significance in surgical series compared with the Universal Definitions of Myocardial Infarction, Dr. Myers said.

“What’s interesting is that for thrombus and bleeding, they require clinical correlation, but on the perioperative MI they now use a definition that does not require clinical significance, meaning no ECG changes, no regional wall motion abnormalities or things like that,” he observed.

The decision also seems to disregard the EXCEL trial controversy that illustrated how outcomes and a trial’s message can change depending on which definition of periprocedural MI is used.

With regard to bleeding, the surgical associations agree with the VARC-3 recommendation to use different thresholds when bleeding is integrated into a composite endpoint (type 2 or greater for TAVR and types 3 or greater for SAVR) but suggest this important point should be featured in the chapter on bleeding rather than the section on composite endpoints.

The surgical associations say VARC-3 also got it right adding the need for a new permanent pacemaker to the early composite safety endpoint, but that it was a “missed opportunity” not to include new left bundle-branch block in the safety composite, despite recognizing that this may become an important endpoint to consider in the future.

Dr. Myers said that left bundle-branch block could have implications for survival as TAVR moves into lower-risk, younger patients, as some data with 1-year follow-up suggest it has a prognostic impact, even in the higher-risk older patients with more competing risks.

Finally, the surgical associations point out that only two of the 23 VARC-3 authors were practicing cardiac surgeons and say that a more diverse writing group “may help mitigate issues related to the duality of interests.”

Dr. Généreux said that the final author list is not a reflection of the rigorous work done by 11 cardiac surgeons including the two surgeon authors. The VARC-3 writing committee also had a good representation of women, unlike the surgical position statement, which was penned by eight men.

Dr. Myers reported no relevant financial relationships. Coauthors disclosed ties with EACTS, Edwards Lifesciences, Medtronic, Abbott Vascular, Boston Scientific, CryoLife, Shockwave, and JenaValve. Dr. Généreux disclosed ties with Abbott Vascular, Abiomed, Boston Scientific, Cardinal Health, Cardiovascular Systems, Edwards Lifesciences, Medtronic, Opsens, Siemens, SoundBite Medical Solutions, Sig.Num, Saranas, Teleflex, Tryton Medical, Pi-Cardia, and Puzzle Medical.

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

Five international cardiac surgery associations have banded together to address “substantive concerns” regarding the recently updated Valve Academic Research Consortium 3 (VARC-3) clinical endpoint definitions for aortic valve research.

The VARC-3 update was a multidisciplinary effort that included more than a dozen new or modified definitions for use in transcatheter and surgical aortic valve replacement (TAVR/SAVR) clinical trials, but drew criticism last year from surgeons that some of its definitions favor TAVR over surgery and that its writing committee had deep ties to industry and lacked diversity.

The new surgical associations’ position statement calls out five specific VARC-3 definitions – rehospitalization, valve thrombosis, bleeding, myocardial infarction (MI), and left bundle-branch block (LBBB).

The statement was jointly issued by the Society of Thoracic Surgeons (STS), the American Association for Thoracic Surgery, the European Association for Cardio-Thoracic Surgery, the Asian Society for Cardiovascular and Thoracic Surgery, and the Latin American Association of Cardiac and Endovascular Surgery.

It was copublished in Annals of Thoracic Surgery, the Journal of Thoracic and Cardiovascular Surgery, the European Journal of Cardio-Thoracic Surgery, and the Asian Cardiovascular and Thoracic Annals.

“We hope that this message can be seen, even if it’s somewhat difficult to hear sometimes, as positive constructive criticism compared to some of the dialogue that we’ve had on social media,” lead author Patrick O. Myers, MD, Lausanne (Switzerland) University Hospital, said in an interview. “It’s not criticizing people or the process but just trying to make these definitions better to ensure the good design of clinical trials.”

The president of each surgical association recommended representatives to help write the position statement, and once completed over Zoom meetings, it received formal endorsement from each association prior to publication, he said.

Reached for comment, VARC-3 lead author Philippe Généreux, MD, Gagnon Cardiovascular Institute, Morristown (N.J.) Medical Center, said, “I was pleasantly surprised that their comments were actually pretty minor and that most of these comments are really more a reflection, not of the validity of the definitions, but rather their applications.”

He noted that all the potential issues with the definitions were already discussed during the making of VARC-3 and resolved by consensus of more than 50 experts including the STS president at the time, Food and Drug Administration officials, and experts from the community.

“To be quite honest, I’m not sure they have consensus,” Dr. Généreux said. He added that the writing committee welcomes input from anyone, but “we’re not going to change the definitions to please eight individuals if we strongly believe by consensus of experts in the field that this is not the right thing to do.”

Rehospitalizations and valve thrombosis

The surgical associations praise VARC-3 for providing a standardized definition of bioprosthetic valve failure, but say they will not endorse the inclusion of rehospitalization as a component of the primary efficacy composite endpoint along with all-cause mortality, stroke, and quality of life.

They note that rehospitalizations outnumber mortality events, especially in short follow-up trials, and that the superiority of TAVR at 1 year in the PARTNER 3 trial of low-risk patients was driven primarily by more rehospitalizations in the surgical arm, but that this superiority was waning at 2 years of follow-up.

“The first thing we are calling for is that it shouldn’t be part of the primary composite outcome measure,” Dr. Myers said. But if it really has to be included, a 30-day blanking period for rehospitalization “would acknowledge that there’s a greater risk of rehospitalization during the acute phase of recovering from surgery.”

Dr. Généreux said that VARC-3 provides granular details for defining the different types of hospitalizations, but that a 30-day blanking period makes no sense. “If you close your eyes to anything within 30 days because you don’t like it, you’re missing the opportunity to improve your procedure, to improve your treatment, and to characterize precisely what happened with your patient.”

The new document lauds VARC-3’s focus on patient-centered and clinically relevant endpoints but questions the definition of valve thrombosis as a “clinically significant” thrombus. It points out that the incidence of valve thrombosis was significantly higher with TAVR versus SAVR in PARTNER 3 using the older VARC-2 definition, which did not require evidence of clinical sequelae (2.6% vs. 0.7%; P = .02). Under the new definition, however, half of the thrombi would be relabeled as “nothing there,” Dr. Myers said.

“As we’re doing this in younger and younger patients who will survive longer, there is a question of thrombus having an effect on the valve and leading to earlier structural valve deterioration,” he added. “All this is conjecture. We don’t have the data. So mainly what we’re advocating is that all thrombi should be reported.”
 

MIs, bleeding, and LBBB

The policy statement also criticizes VARC-3’s decision to define periprocedural (type 5) MI using a biomarker-only definition without need of clinical confirmation. Such definitions have been shown to have a very poor prognostic significance in surgical series compared with the Universal Definitions of Myocardial Infarction, Dr. Myers said.

“What’s interesting is that for thrombus and bleeding, they require clinical correlation, but on the perioperative MI they now use a definition that does not require clinical significance, meaning no ECG changes, no regional wall motion abnormalities or things like that,” he observed.

The decision also seems to disregard the EXCEL trial controversy that illustrated how outcomes and a trial’s message can change depending on which definition of periprocedural MI is used.

With regard to bleeding, the surgical associations agree with the VARC-3 recommendation to use different thresholds when bleeding is integrated into a composite endpoint (type 2 or greater for TAVR and types 3 or greater for SAVR) but suggest this important point should be featured in the chapter on bleeding rather than the section on composite endpoints.

The surgical associations say VARC-3 also got it right adding the need for a new permanent pacemaker to the early composite safety endpoint, but that it was a “missed opportunity” not to include new left bundle-branch block in the safety composite, despite recognizing that this may become an important endpoint to consider in the future.

Dr. Myers said that left bundle-branch block could have implications for survival as TAVR moves into lower-risk, younger patients, as some data with 1-year follow-up suggest it has a prognostic impact, even in the higher-risk older patients with more competing risks.

Finally, the surgical associations point out that only two of the 23 VARC-3 authors were practicing cardiac surgeons and say that a more diverse writing group “may help mitigate issues related to the duality of interests.”

Dr. Généreux said that the final author list is not a reflection of the rigorous work done by 11 cardiac surgeons including the two surgeon authors. The VARC-3 writing committee also had a good representation of women, unlike the surgical position statement, which was penned by eight men.

Dr. Myers reported no relevant financial relationships. Coauthors disclosed ties with EACTS, Edwards Lifesciences, Medtronic, Abbott Vascular, Boston Scientific, CryoLife, Shockwave, and JenaValve. Dr. Généreux disclosed ties with Abbott Vascular, Abiomed, Boston Scientific, Cardinal Health, Cardiovascular Systems, Edwards Lifesciences, Medtronic, Opsens, Siemens, SoundBite Medical Solutions, Sig.Num, Saranas, Teleflex, Tryton Medical, Pi-Cardia, and Puzzle Medical.

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

A congressional oversight subcommittee is investigating the Food and Drug Administration’s regulation of a high-risk heart pump, citing safety issues detailed by ProPublica.

The HeartWare Ventricular Assist Device, created to treat patients with severe heart failure, stopped meeting key federal standards as early as 2014. But the FDA took no decisive action even as those problems persisted, and thousands of Americans continued to be implanted with the pump.

By the end of 2020, the FDA had received more than 3,000 reports of deaths related to the HeartWare device, according to a ProPublica data analysis. A father of four died as his children tried to resuscitate him when his device suddenly stopped. A teenager died after vomiting blood in the middle of the night, while his mother struggled to restart a faulty pump.

“I am concerned by FDA’s slow action, over multiple administrations, to protect patients from this product despite early warning signs,” Rep. Raja Krishnamoorthi, D-Ill., said in a scathing letter sent March 22 to the agency’s commissioner, Robert Califf, MD.

Mr. Krishnamoorthi, the chairman of the U.S. House Committee on Oversight and Reform’s Subcommittee on Economic and Consumer Policy, requested information on how the FDA made regulatory decisions related to the HeartWare device and why it didn’t take further action.

The FDA did not provide comment to ProPublica on the subcommittee’s investigation and said it would respond directly to Mr. Krishnamoorthi. It also reiterated its response to ProPublica’s findings and said the agency had been closely overseeing the HeartWare device since 2012, with patient safety as its “highest priority.”

Medtronic, the company that acquired HeartWare in 2016, took the device off the market in June 2021. The company said that new data showed a competing heart pump had better outcomes. In response to the ProPublica investigation 2 months later, the company said it took the FDA’s inspections seriously and had worked closely with the agency to address issues with the device.

Medtronic declined to comment on the subcommittee’s investigation.

Mr. Krishnamoorthi asked in the letter if any steps were being taken to address how patients, doctors and other federal agencies are notified of problems that the FDA finds with medical devices.

Many patients told ProPublica they were never informed of issues with the HeartWare pump before or after their implants. Some people who still have the device said they weren’t told when it was taken off the market. Medtronic said in December it had confirmed 90% of U.S. patients had received notification of the HeartWare discontinuation, but that it was still working to reach the other 10%.

About 2,000 patients still had HeartWare pumps as of last year. The FDA and Medtronic recommended against removing those devices barring medical necessity because the surgery to do so carries a high risk.

In his letter, Mr. Krishnamoorthi gave the FDA a deadline of April 5 to respond.
 

This story was originally published on ProPublica. ProPublica is a nonprofit newsroom that investigates abuses of power. Sign up to receive their biggest stories as soon as they’re published.

A congressional oversight subcommittee is investigating the Food and Drug Administration’s regulation of a high-risk heart pump, citing safety issues detailed by ProPublica.

The HeartWare Ventricular Assist Device, created to treat patients with severe heart failure, stopped meeting key federal standards as early as 2014. But the FDA took no decisive action even as those problems persisted, and thousands of Americans continued to be implanted with the pump.

By the end of 2020, the FDA had received more than 3,000 reports of deaths related to the HeartWare device, according to a ProPublica data analysis. A father of four died as his children tried to resuscitate him when his device suddenly stopped. A teenager died after vomiting blood in the middle of the night, while his mother struggled to restart a faulty pump.

“I am concerned by FDA’s slow action, over multiple administrations, to protect patients from this product despite early warning signs,” Rep. Raja Krishnamoorthi, D-Ill., said in a scathing letter sent March 22 to the agency’s commissioner, Robert Califf, MD.

Mr. Krishnamoorthi, the chairman of the U.S. House Committee on Oversight and Reform’s Subcommittee on Economic and Consumer Policy, requested information on how the FDA made regulatory decisions related to the HeartWare device and why it didn’t take further action.

The FDA did not provide comment to ProPublica on the subcommittee’s investigation and said it would respond directly to Mr. Krishnamoorthi. It also reiterated its response to ProPublica’s findings and said the agency had been closely overseeing the HeartWare device since 2012, with patient safety as its “highest priority.”

Medtronic, the company that acquired HeartWare in 2016, took the device off the market in June 2021. The company said that new data showed a competing heart pump had better outcomes. In response to the ProPublica investigation 2 months later, the company said it took the FDA’s inspections seriously and had worked closely with the agency to address issues with the device.

Medtronic declined to comment on the subcommittee’s investigation.

Mr. Krishnamoorthi asked in the letter if any steps were being taken to address how patients, doctors and other federal agencies are notified of problems that the FDA finds with medical devices.

Many patients told ProPublica they were never informed of issues with the HeartWare pump before or after their implants. Some people who still have the device said they weren’t told when it was taken off the market. Medtronic said in December it had confirmed 90% of U.S. patients had received notification of the HeartWare discontinuation, but that it was still working to reach the other 10%.

About 2,000 patients still had HeartWare pumps as of last year. The FDA and Medtronic recommended against removing those devices barring medical necessity because the surgery to do so carries a high risk.

In his letter, Mr. Krishnamoorthi gave the FDA a deadline of April 5 to respond.
 

This story was originally published on ProPublica. ProPublica is a nonprofit newsroom that investigates abuses of power. Sign up to receive their biggest stories as soon as they’re published.

A congressional oversight subcommittee is investigating the Food and Drug Administration’s regulation of a high-risk heart pump, citing safety issues detailed by ProPublica.

The HeartWare Ventricular Assist Device, created to treat patients with severe heart failure, stopped meeting key federal standards as early as 2014. But the FDA took no decisive action even as those problems persisted, and thousands of Americans continued to be implanted with the pump.

By the end of 2020, the FDA had received more than 3,000 reports of deaths related to the HeartWare device, according to a ProPublica data analysis. A father of four died as his children tried to resuscitate him when his device suddenly stopped. A teenager died after vomiting blood in the middle of the night, while his mother struggled to restart a faulty pump.

“I am concerned by FDA’s slow action, over multiple administrations, to protect patients from this product despite early warning signs,” Rep. Raja Krishnamoorthi, D-Ill., said in a scathing letter sent March 22 to the agency’s commissioner, Robert Califf, MD.

Mr. Krishnamoorthi, the chairman of the U.S. House Committee on Oversight and Reform’s Subcommittee on Economic and Consumer Policy, requested information on how the FDA made regulatory decisions related to the HeartWare device and why it didn’t take further action.

The FDA did not provide comment to ProPublica on the subcommittee’s investigation and said it would respond directly to Mr. Krishnamoorthi. It also reiterated its response to ProPublica’s findings and said the agency had been closely overseeing the HeartWare device since 2012, with patient safety as its “highest priority.”

Medtronic, the company that acquired HeartWare in 2016, took the device off the market in June 2021. The company said that new data showed a competing heart pump had better outcomes. In response to the ProPublica investigation 2 months later, the company said it took the FDA’s inspections seriously and had worked closely with the agency to address issues with the device.

Medtronic declined to comment on the subcommittee’s investigation.

Mr. Krishnamoorthi asked in the letter if any steps were being taken to address how patients, doctors and other federal agencies are notified of problems that the FDA finds with medical devices.

Many patients told ProPublica they were never informed of issues with the HeartWare pump before or after their implants. Some people who still have the device said they weren’t told when it was taken off the market. Medtronic said in December it had confirmed 90% of U.S. patients had received notification of the HeartWare discontinuation, but that it was still working to reach the other 10%.

About 2,000 patients still had HeartWare pumps as of last year. The FDA and Medtronic recommended against removing those devices barring medical necessity because the surgery to do so carries a high risk.

In his letter, Mr. Krishnamoorthi gave the FDA a deadline of April 5 to respond.
 

This story was originally published on ProPublica. ProPublica is a nonprofit newsroom that investigates abuses of power. Sign up to receive their biggest stories as soon as they’re published.

A sudden drop in blood pressure when standing is a common and concerning problem in elderly hypertensive people. Now, research suggests a large BP swing in the opposite direction on standing may be equally concerning in younger hypertensive people.

Young and middle-aged adults with a systolic BP response to standing greater than 6.5 mm Hg had almost double the risk of major adverse cardiovascular events (MACE) during follow-up, compared with other participants.

An exaggerated BP response remained an independent predictor of MACE, even after adjusting for traditional risk factors, including 24-hour BP (hazard ratio, 1.94; 95% confidence interval, 1.10 to 3.44), the study showed.

“The clinical implication is important, because now doctors measure blood pressure in young people in the upright posture, but what we say is it must be measured also while standing,” said Paolo Palatini, MD, a professor of internal medicine at the University of Padova, Italy, who led the study.

Previous studies have found that an exaggerated BP response to standing is a predictor of future hypertension, CV events, and mortality, particularly in older patients, but few prognostic data exist in those who are young to middle age, he noted.

The study, published in Hypertension, included 1,207 participants ages 18-45 years with untreated stage 1 hypertension (systolic BP 140-159 mm Hg or diastolic BP 90-100 mm Hg) in the prospective multicenter HARVEST study that began in Italy in 1990. The average age at enrollment was 33 years.

BP was measured at two visits 2 weeks apart, with each visit including three supine measurements taken after the patient had lain down for a minimum of 5 minutes, followed by three standing measurements taken 1 minute apart.

Based on the average of standing-lying BP differences during the two visits, participants were then classified as having a normal or exaggerated (top decile, lower limit > 6.5 mm Hg) systolic BP response to standing.

The 120 participants classified as “hyper-reactors” averaged an 11.4 mm Hg systolic BP increase upon standing, whereas the rest of the participants averaged a 3.8 mm Hg fall in systolic BP upon standing.

At their initial visit, hyper-reactors were more likely to be smokers (32.1% vs. 19.9%) and coffee drinkers (81.7% vs. 73%) and to have ambulatory hypertension (90.8% vs. 76.4%).

They were, however, no more likely to have a family history of cardiovascular events and had a lower supine systolic BP (140.5 mm Hg vs. 146.0 mm Hg), lower total cholesterol (4.93 mmol/L vs. 5.13 mmol/L), and higher HDL cholesterol (1.42 mmol/L vs. 1.35 mmol/L).

Age, sex, and body mass index were similar between the two groups, as was BP variability, nocturnal BP dip, and the frequency of extreme dippers. Participants with a normal systolic BP response were more likely to be treated for hypertension during follow-up (81.7% vs. 69.7%; P = .003).

In 630 participants who had catecholamines measured from 24-hour urine samples, the epinephrine/creatinine ratio was higher in hyper-reactors than normal responders (118.4 nmol/mol vs. 77.0 nmol/mol; P = .005).

During a median follow-up of 17.3 years, there were 105 major cardiovascular events, broadly defined to include acute coronary syndromes (48), any stroke (13), heart failure requiring hospitalization (3), aortic aneurysms (3), peripheral vascular disease (6), chronic kidney disease (12), and permanent atrial fibrillation (20).

The near doubling of MACE risk among hyper-reactors remained when atrial fibrillation was excluded and when 24-hour ambulatory systolic BP was included in the model, the author reported.

The results are in line with previous studies, indicating that hyper-reactors to standing have normal sympathetic activity at rest but an increased sympathetic response to stressors, observed Dr. Palatini and colleagues. This neurohumoral overshoot seems to be peculiar to young adults, whereas vascular stiffness seems to be the driving mechanism of orthostatic hypertension in older adults.

If a young person’s BP spikes upon standing, “then you have to treat them according to the average of the lying and the standing pressure,” Dr. Palatini said. “In these people, blood pressure should be treated earlier than in the past.”

“The study is important because it identified a new marker for hypertension that is easily evaluated in clinical practice,” Nieca Goldberg, MD, medical director of the Atria Institute, New York, and an associate professor of medicine at New York University Grossman School of Medicine, commented via email.

She noted that standing blood pressures are usually not taken as part of a medical visit and, in fact, seated blood pressures are often taken incorrectly while the patient is seated on the exam table rather than with their feet on the floor and using the proper cuff size.

“By incorporating standing BP, we will improve our diagnosis for hypertension, and with interventions such as diet and exercise, salt reduction, and medication when indicated, lower risk for heart attack, stroke, heart failure, [and] kidney and eye disease,” said Dr. Goldberg, who is also a spokesperson for the American Heart Association.

“The biggest barrier is that office visits are limited to 15 minutes, and not enough time is spent on the vital signs,” she noted. “We need changes to the health care system that value our ability to diagnose BP and take the time to counsel patients and explain treatment options.”

Limitations of the present study are that 72.7% of participants were men and all were White, Dr. Palatini said. Future work is also needed to create a uniform definition of BP hyper-reactivity to standing, possibly based on risk estimates, for inclusion in future hypertension guidelines.

The study was funded by the Association 18 Maggio 1370 in Italy. The authors have disclosed no relevant financial relationships. Dr. Goldberg reported being a spokesperson for the American Heart Association.

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

A sudden drop in blood pressure when standing is a common and concerning problem in elderly hypertensive people. Now, research suggests a large BP swing in the opposite direction on standing may be equally concerning in younger hypertensive people.

Young and middle-aged adults with a systolic BP response to standing greater than 6.5 mm Hg had almost double the risk of major adverse cardiovascular events (MACE) during follow-up, compared with other participants.

An exaggerated BP response remained an independent predictor of MACE, even after adjusting for traditional risk factors, including 24-hour BP (hazard ratio, 1.94; 95% confidence interval, 1.10 to 3.44), the study showed.

“The clinical implication is important, because now doctors measure blood pressure in young people in the upright posture, but what we say is it must be measured also while standing,” said Paolo Palatini, MD, a professor of internal medicine at the University of Padova, Italy, who led the study.

Previous studies have found that an exaggerated BP response to standing is a predictor of future hypertension, CV events, and mortality, particularly in older patients, but few prognostic data exist in those who are young to middle age, he noted.

The study, published in Hypertension, included 1,207 participants ages 18-45 years with untreated stage 1 hypertension (systolic BP 140-159 mm Hg or diastolic BP 90-100 mm Hg) in the prospective multicenter HARVEST study that began in Italy in 1990. The average age at enrollment was 33 years.

BP was measured at two visits 2 weeks apart, with each visit including three supine measurements taken after the patient had lain down for a minimum of 5 minutes, followed by three standing measurements taken 1 minute apart.

Based on the average of standing-lying BP differences during the two visits, participants were then classified as having a normal or exaggerated (top decile, lower limit > 6.5 mm Hg) systolic BP response to standing.

The 120 participants classified as “hyper-reactors” averaged an 11.4 mm Hg systolic BP increase upon standing, whereas the rest of the participants averaged a 3.8 mm Hg fall in systolic BP upon standing.

At their initial visit, hyper-reactors were more likely to be smokers (32.1% vs. 19.9%) and coffee drinkers (81.7% vs. 73%) and to have ambulatory hypertension (90.8% vs. 76.4%).

They were, however, no more likely to have a family history of cardiovascular events and had a lower supine systolic BP (140.5 mm Hg vs. 146.0 mm Hg), lower total cholesterol (4.93 mmol/L vs. 5.13 mmol/L), and higher HDL cholesterol (1.42 mmol/L vs. 1.35 mmol/L).

Age, sex, and body mass index were similar between the two groups, as was BP variability, nocturnal BP dip, and the frequency of extreme dippers. Participants with a normal systolic BP response were more likely to be treated for hypertension during follow-up (81.7% vs. 69.7%; P = .003).

In 630 participants who had catecholamines measured from 24-hour urine samples, the epinephrine/creatinine ratio was higher in hyper-reactors than normal responders (118.4 nmol/mol vs. 77.0 nmol/mol; P = .005).

During a median follow-up of 17.3 years, there were 105 major cardiovascular events, broadly defined to include acute coronary syndromes (48), any stroke (13), heart failure requiring hospitalization (3), aortic aneurysms (3), peripheral vascular disease (6), chronic kidney disease (12), and permanent atrial fibrillation (20).

The near doubling of MACE risk among hyper-reactors remained when atrial fibrillation was excluded and when 24-hour ambulatory systolic BP was included in the model, the author reported.

The results are in line with previous studies, indicating that hyper-reactors to standing have normal sympathetic activity at rest but an increased sympathetic response to stressors, observed Dr. Palatini and colleagues. This neurohumoral overshoot seems to be peculiar to young adults, whereas vascular stiffness seems to be the driving mechanism of orthostatic hypertension in older adults.

If a young person’s BP spikes upon standing, “then you have to treat them according to the average of the lying and the standing pressure,” Dr. Palatini said. “In these people, blood pressure should be treated earlier than in the past.”

“The study is important because it identified a new marker for hypertension that is easily evaluated in clinical practice,” Nieca Goldberg, MD, medical director of the Atria Institute, New York, and an associate professor of medicine at New York University Grossman School of Medicine, commented via email.

She noted that standing blood pressures are usually not taken as part of a medical visit and, in fact, seated blood pressures are often taken incorrectly while the patient is seated on the exam table rather than with their feet on the floor and using the proper cuff size.

“By incorporating standing BP, we will improve our diagnosis for hypertension, and with interventions such as diet and exercise, salt reduction, and medication when indicated, lower risk for heart attack, stroke, heart failure, [and] kidney and eye disease,” said Dr. Goldberg, who is also a spokesperson for the American Heart Association.

“The biggest barrier is that office visits are limited to 15 minutes, and not enough time is spent on the vital signs,” she noted. “We need changes to the health care system that value our ability to diagnose BP and take the time to counsel patients and explain treatment options.”

Limitations of the present study are that 72.7% of participants were men and all were White, Dr. Palatini said. Future work is also needed to create a uniform definition of BP hyper-reactivity to standing, possibly based on risk estimates, for inclusion in future hypertension guidelines.

The study was funded by the Association 18 Maggio 1370 in Italy. The authors have disclosed no relevant financial relationships. Dr. Goldberg reported being a spokesperson for the American Heart Association.

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

A sudden drop in blood pressure when standing is a common and concerning problem in elderly hypertensive people. Now, research suggests a large BP swing in the opposite direction on standing may be equally concerning in younger hypertensive people.

Young and middle-aged adults with a systolic BP response to standing greater than 6.5 mm Hg had almost double the risk of major adverse cardiovascular events (MACE) during follow-up, compared with other participants.

An exaggerated BP response remained an independent predictor of MACE, even after adjusting for traditional risk factors, including 24-hour BP (hazard ratio, 1.94; 95% confidence interval, 1.10 to 3.44), the study showed.

“The clinical implication is important, because now doctors measure blood pressure in young people in the upright posture, but what we say is it must be measured also while standing,” said Paolo Palatini, MD, a professor of internal medicine at the University of Padova, Italy, who led the study.

Previous studies have found that an exaggerated BP response to standing is a predictor of future hypertension, CV events, and mortality, particularly in older patients, but few prognostic data exist in those who are young to middle age, he noted.

The study, published in Hypertension, included 1,207 participants ages 18-45 years with untreated stage 1 hypertension (systolic BP 140-159 mm Hg or diastolic BP 90-100 mm Hg) in the prospective multicenter HARVEST study that began in Italy in 1990. The average age at enrollment was 33 years.

BP was measured at two visits 2 weeks apart, with each visit including three supine measurements taken after the patient had lain down for a minimum of 5 minutes, followed by three standing measurements taken 1 minute apart.

Based on the average of standing-lying BP differences during the two visits, participants were then classified as having a normal or exaggerated (top decile, lower limit > 6.5 mm Hg) systolic BP response to standing.

The 120 participants classified as “hyper-reactors” averaged an 11.4 mm Hg systolic BP increase upon standing, whereas the rest of the participants averaged a 3.8 mm Hg fall in systolic BP upon standing.

At their initial visit, hyper-reactors were more likely to be smokers (32.1% vs. 19.9%) and coffee drinkers (81.7% vs. 73%) and to have ambulatory hypertension (90.8% vs. 76.4%).

They were, however, no more likely to have a family history of cardiovascular events and had a lower supine systolic BP (140.5 mm Hg vs. 146.0 mm Hg), lower total cholesterol (4.93 mmol/L vs. 5.13 mmol/L), and higher HDL cholesterol (1.42 mmol/L vs. 1.35 mmol/L).

Age, sex, and body mass index were similar between the two groups, as was BP variability, nocturnal BP dip, and the frequency of extreme dippers. Participants with a normal systolic BP response were more likely to be treated for hypertension during follow-up (81.7% vs. 69.7%; P = .003).

In 630 participants who had catecholamines measured from 24-hour urine samples, the epinephrine/creatinine ratio was higher in hyper-reactors than normal responders (118.4 nmol/mol vs. 77.0 nmol/mol; P = .005).

During a median follow-up of 17.3 years, there were 105 major cardiovascular events, broadly defined to include acute coronary syndromes (48), any stroke (13), heart failure requiring hospitalization (3), aortic aneurysms (3), peripheral vascular disease (6), chronic kidney disease (12), and permanent atrial fibrillation (20).

The near doubling of MACE risk among hyper-reactors remained when atrial fibrillation was excluded and when 24-hour ambulatory systolic BP was included in the model, the author reported.

The results are in line with previous studies, indicating that hyper-reactors to standing have normal sympathetic activity at rest but an increased sympathetic response to stressors, observed Dr. Palatini and colleagues. This neurohumoral overshoot seems to be peculiar to young adults, whereas vascular stiffness seems to be the driving mechanism of orthostatic hypertension in older adults.

If a young person’s BP spikes upon standing, “then you have to treat them according to the average of the lying and the standing pressure,” Dr. Palatini said. “In these people, blood pressure should be treated earlier than in the past.”

“The study is important because it identified a new marker for hypertension that is easily evaluated in clinical practice,” Nieca Goldberg, MD, medical director of the Atria Institute, New York, and an associate professor of medicine at New York University Grossman School of Medicine, commented via email.

She noted that standing blood pressures are usually not taken as part of a medical visit and, in fact, seated blood pressures are often taken incorrectly while the patient is seated on the exam table rather than with their feet on the floor and using the proper cuff size.

“By incorporating standing BP, we will improve our diagnosis for hypertension, and with interventions such as diet and exercise, salt reduction, and medication when indicated, lower risk for heart attack, stroke, heart failure, [and] kidney and eye disease,” said Dr. Goldberg, who is also a spokesperson for the American Heart Association.

“The biggest barrier is that office visits are limited to 15 minutes, and not enough time is spent on the vital signs,” she noted. “We need changes to the health care system that value our ability to diagnose BP and take the time to counsel patients and explain treatment options.”

Limitations of the present study are that 72.7% of participants were men and all were White, Dr. Palatini said. Future work is also needed to create a uniform definition of BP hyper-reactivity to standing, possibly based on risk estimates, for inclusion in future hypertension guidelines.

The study was funded by the Association 18 Maggio 1370 in Italy. The authors have disclosed no relevant financial relationships. Dr. Goldberg reported being a spokesperson for the American Heart Association.

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

Pfizer is voluntarily recalling some antihypertensive medications because of unacceptable levels of a potential carcinogen, the company announced. 

The affected products are quinapril HCI/hydrochlorothiazide (Accuretic) tablets that Pfizer distributes, and two authorized generics, quinapril plus hydrochlorothiazide and quinapril HCI/hydrochlorothiazide, distributed by Greenstone. The drugs have been withdrawn because of the presence of nitrosamine, N-nitroso-quinapril.

“Although long-term ingestion of N-nitroso-quinapril may be associated with a potential increased cancer risk in humans, there is no immediate risk to patients taking this medication,” Pfizer said in a news release.

The tablets are indicated for the treatment of hypertension. Patients currently taking the products are asked to consult with their doctor about alternative treatment options.

To date, there have been no reports of adverse events related to the recall, the company said.

In all, Pfizer is recalling six lots of Accuretic tablets (two at 10 mg/12.5 mg, three at 20 mg/12.5 mg, and one at 20 mg/25 mg), one lot of quinapril plus hydrochlorothiazide 20-mg/25-mg tablets, and four lots of quinapril HCl/ hydrochlorothiazide tablets (three at 20 mg/12.5 mg and one at 20 mg/25 mg)

The recalled tablets were sold in 90-count bottles distributed in the United States and Puerto Rico between November 2019 and March 2022. Product codes and lot numbers of the recalled medications are listed on the Pfizer website.

Patients who are taking this product should consult with their health care provider or pharmacy to determine if they have the affected product. Those with the affected tablets should contact claims management firm Sedgwick by phone at 888-843-0247 Monday through Friday from 8 a.m. to 5 p.m. ET for instructions on how to return their product and obtain reimbursement.

Health care providers with medical questions regarding the recall can contact Pfizer by telephone at 800-438-1985, option 3, Monday through Friday 8 a.m. to 9 p.m. ET.

Providers should report adverse reactions or quality problems they experience using these tablets to Pfizer either by telephone at 800-438-1985, option 1, by regular mail or by fax, or to the Food and Drug Administration’s MedWatch program.

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

Pfizer is voluntarily recalling some antihypertensive medications because of unacceptable levels of a potential carcinogen, the company announced. 

The affected products are quinapril HCI/hydrochlorothiazide (Accuretic) tablets that Pfizer distributes, and two authorized generics, quinapril plus hydrochlorothiazide and quinapril HCI/hydrochlorothiazide, distributed by Greenstone. The drugs have been withdrawn because of the presence of nitrosamine, N-nitroso-quinapril.

“Although long-term ingestion of N-nitroso-quinapril may be associated with a potential increased cancer risk in humans, there is no immediate risk to patients taking this medication,” Pfizer said in a news release.

The tablets are indicated for the treatment of hypertension. Patients currently taking the products are asked to consult with their doctor about alternative treatment options.

To date, there have been no reports of adverse events related to the recall, the company said.

In all, Pfizer is recalling six lots of Accuretic tablets (two at 10 mg/12.5 mg, three at 20 mg/12.5 mg, and one at 20 mg/25 mg), one lot of quinapril plus hydrochlorothiazide 20-mg/25-mg tablets, and four lots of quinapril HCl/ hydrochlorothiazide tablets (three at 20 mg/12.5 mg and one at 20 mg/25 mg)

The recalled tablets were sold in 90-count bottles distributed in the United States and Puerto Rico between November 2019 and March 2022. Product codes and lot numbers of the recalled medications are listed on the Pfizer website.

Patients who are taking this product should consult with their health care provider or pharmacy to determine if they have the affected product. Those with the affected tablets should contact claims management firm Sedgwick by phone at 888-843-0247 Monday through Friday from 8 a.m. to 5 p.m. ET for instructions on how to return their product and obtain reimbursement.

Health care providers with medical questions regarding the recall can contact Pfizer by telephone at 800-438-1985, option 3, Monday through Friday 8 a.m. to 9 p.m. ET.

Providers should report adverse reactions or quality problems they experience using these tablets to Pfizer either by telephone at 800-438-1985, option 1, by regular mail or by fax, or to the Food and Drug Administration’s MedWatch program.

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

Pfizer is voluntarily recalling some antihypertensive medications because of unacceptable levels of a potential carcinogen, the company announced. 

The affected products are quinapril HCI/hydrochlorothiazide (Accuretic) tablets that Pfizer distributes, and two authorized generics, quinapril plus hydrochlorothiazide and quinapril HCI/hydrochlorothiazide, distributed by Greenstone. The drugs have been withdrawn because of the presence of nitrosamine, N-nitroso-quinapril.

“Although long-term ingestion of N-nitroso-quinapril may be associated with a potential increased cancer risk in humans, there is no immediate risk to patients taking this medication,” Pfizer said in a news release.

The tablets are indicated for the treatment of hypertension. Patients currently taking the products are asked to consult with their doctor about alternative treatment options.

To date, there have been no reports of adverse events related to the recall, the company said.

In all, Pfizer is recalling six lots of Accuretic tablets (two at 10 mg/12.5 mg, three at 20 mg/12.5 mg, and one at 20 mg/25 mg), one lot of quinapril plus hydrochlorothiazide 20-mg/25-mg tablets, and four lots of quinapril HCl/ hydrochlorothiazide tablets (three at 20 mg/12.5 mg and one at 20 mg/25 mg)

The recalled tablets were sold in 90-count bottles distributed in the United States and Puerto Rico between November 2019 and March 2022. Product codes and lot numbers of the recalled medications are listed on the Pfizer website.

Patients who are taking this product should consult with their health care provider or pharmacy to determine if they have the affected product. Those with the affected tablets should contact claims management firm Sedgwick by phone at 888-843-0247 Monday through Friday from 8 a.m. to 5 p.m. ET for instructions on how to return their product and obtain reimbursement.

Health care providers with medical questions regarding the recall can contact Pfizer by telephone at 800-438-1985, option 3, Monday through Friday 8 a.m. to 9 p.m. ET.

Providers should report adverse reactions or quality problems they experience using these tablets to Pfizer either by telephone at 800-438-1985, option 1, by regular mail or by fax, or to the Food and Drug Administration’s MedWatch program.

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

Researchers running the EMPA-KIDNEY trial that’s been testing the safety and efficacy of the SGLT2 inhibitor empagliflozin (Jardiance) in about 6,600 patients with chronic kidney disease (CKD) announced on March 16 that they had stopped the trial early because of positive efficacy that met the study’s prespecified threshold for early termination.

EMPA-KIDNEY is the third major trial of an agent from the sodium-glucose cotransport 2 (SGLT2) inhibitor class tested in patients with CKD to be stopped early because of positive results that met a prespecified termination rule.

HYWARDS/Getty Images

EMPA-KIDNEY enrolled a wider range of patients

EMPA-KIDNEY expands the scope of types of patients with CKD now shown to benefit from treatment with an SGLT2 inhibitor. CREDENCE tested canagliflozin only in patients with type 2 diabetes and diabetic nephropathy, and in DAPA-CKD, two-thirds of enrolled patients had type 2 diabetes, and all had CKD. In EMPA-KIDNEY, 46% of the 6,609 enrolled patients had diabetes (including a very small number with type 1 diabetes).

Another departure from prior studies of an SGLT2 inhibitor for patients selected primarily for having CKD was that in EMPA-KIDNEY, 20% of patients did not have albuminuria, and for 34%, eGFR at entry was less than 30 mL/min/1.73 m², with all enrolled patients required to have an eGFR at entry of greater than or equal to 20 mL/min/1.73 m². Average eGFR in EMPA-KIDNEY was about 38 mL/min/1.73 m². To be included in the trial, patients were not required to have albuminuria, except those whose eGFR was greater than or equal to 45 mL/min/1.73 m².

In DAPA-CKD, the minimum eGFR at entry had to be greater than or equal to 25 mL/min/1.73 m², and roughly 14% of enrolled patients had an eGFR of less than 30 mL/min/1.73 m². The average eGFR in DAPA-CKD was about 43 mL/min/1.73 m². In addition, all patients had at least microalbuminuria, with a minimum urinary albumin-to-creatinine ratio of 200. In CREDENCE, the minimum eGFR for enrollment was 30 mL/min/1.73 m², and the average eGFR was about 56 mL/min/1.73 m². All patients in CREDENCE had to have macroalbuminuria, with a urinary albumin-to-creatinine ratio of more than 300.

According to the researchers who designed EMPA-KIDNEY, the trial enrollment criteria aimed to include adults with CKD “who are frequently seen in practice but were under-represented in previous SGLT2 inhibitor trials.”

Indications for empagliflozin are expanding

The success of empagliflozin in EMPA-KIDNEY follows its positive results in both the EMPEROR-Reduced and EMPEROR-Preserved trials, which collectively proved the efficacy of the agent for patients with heart failure regardless of their left ventricular ejection fraction and regardless of whether they also had diabetes.

These results led the U.S. Food and Drug Administration to recently expand the labeled indication for empagliflozin to all patients with heart failure. Empagliflozin also has labeled indications for glycemic control in patients with type 2 diabetes and to reduce the risk of cardiovascular death in adults with type 2 diabetes and established cardiovascular disease.

As of today, empagliflozin has no labeled indication for treating patients with CKD. Dapagliflozin received that indication in April 2021, and canagliflozin received an indication for treating patients with type 2 diabetes, diabetic nephropathy, and albuminuria in September 2019.

EMPA-KIDNEY is sponsored by Boehringer Ingelheim and Lilly, the two companies that jointly market empagliflozin (Jardiance).

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

Researchers running the EMPA-KIDNEY trial that’s been testing the safety and efficacy of the SGLT2 inhibitor empagliflozin (Jardiance) in about 6,600 patients with chronic kidney disease (CKD) announced on March 16 that they had stopped the trial early because of positive efficacy that met the study’s prespecified threshold for early termination.

EMPA-KIDNEY is the third major trial of an agent from the sodium-glucose cotransport 2 (SGLT2) inhibitor class tested in patients with CKD to be stopped early because of positive results that met a prespecified termination rule.

HYWARDS/Getty Images

EMPA-KIDNEY enrolled a wider range of patients

EMPA-KIDNEY expands the scope of types of patients with CKD now shown to benefit from treatment with an SGLT2 inhibitor. CREDENCE tested canagliflozin only in patients with type 2 diabetes and diabetic nephropathy, and in DAPA-CKD, two-thirds of enrolled patients had type 2 diabetes, and all had CKD. In EMPA-KIDNEY, 46% of the 6,609 enrolled patients had diabetes (including a very small number with type 1 diabetes).

Another departure from prior studies of an SGLT2 inhibitor for patients selected primarily for having CKD was that in EMPA-KIDNEY, 20% of patients did not have albuminuria, and for 34%, eGFR at entry was less than 30 mL/min/1.73 m², with all enrolled patients required to have an eGFR at entry of greater than or equal to 20 mL/min/1.73 m². Average eGFR in EMPA-KIDNEY was about 38 mL/min/1.73 m². To be included in the trial, patients were not required to have albuminuria, except those whose eGFR was greater than or equal to 45 mL/min/1.73 m².

In DAPA-CKD, the minimum eGFR at entry had to be greater than or equal to 25 mL/min/1.73 m², and roughly 14% of enrolled patients had an eGFR of less than 30 mL/min/1.73 m². The average eGFR in DAPA-CKD was about 43 mL/min/1.73 m². In addition, all patients had at least microalbuminuria, with a minimum urinary albumin-to-creatinine ratio of 200. In CREDENCE, the minimum eGFR for enrollment was 30 mL/min/1.73 m², and the average eGFR was about 56 mL/min/1.73 m². All patients in CREDENCE had to have macroalbuminuria, with a urinary albumin-to-creatinine ratio of more than 300.

According to the researchers who designed EMPA-KIDNEY, the trial enrollment criteria aimed to include adults with CKD “who are frequently seen in practice but were under-represented in previous SGLT2 inhibitor trials.”

Indications for empagliflozin are expanding

The success of empagliflozin in EMPA-KIDNEY follows its positive results in both the EMPEROR-Reduced and EMPEROR-Preserved trials, which collectively proved the efficacy of the agent for patients with heart failure regardless of their left ventricular ejection fraction and regardless of whether they also had diabetes.

These results led the U.S. Food and Drug Administration to recently expand the labeled indication for empagliflozin to all patients with heart failure. Empagliflozin also has labeled indications for glycemic control in patients with type 2 diabetes and to reduce the risk of cardiovascular death in adults with type 2 diabetes and established cardiovascular disease.

As of today, empagliflozin has no labeled indication for treating patients with CKD. Dapagliflozin received that indication in April 2021, and canagliflozin received an indication for treating patients with type 2 diabetes, diabetic nephropathy, and albuminuria in September 2019.

EMPA-KIDNEY is sponsored by Boehringer Ingelheim and Lilly, the two companies that jointly market empagliflozin (Jardiance).

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

Researchers running the EMPA-KIDNEY trial that’s been testing the safety and efficacy of the SGLT2 inhibitor empagliflozin (Jardiance) in about 6,600 patients with chronic kidney disease (CKD) announced on March 16 that they had stopped the trial early because of positive efficacy that met the study’s prespecified threshold for early termination.

EMPA-KIDNEY is the third major trial of an agent from the sodium-glucose cotransport 2 (SGLT2) inhibitor class tested in patients with CKD to be stopped early because of positive results that met a prespecified termination rule.

HYWARDS/Getty Images

EMPA-KIDNEY enrolled a wider range of patients

EMPA-KIDNEY expands the scope of types of patients with CKD now shown to benefit from treatment with an SGLT2 inhibitor. CREDENCE tested canagliflozin only in patients with type 2 diabetes and diabetic nephropathy, and in DAPA-CKD, two-thirds of enrolled patients had type 2 diabetes, and all had CKD. In EMPA-KIDNEY, 46% of the 6,609 enrolled patients had diabetes (including a very small number with type 1 diabetes).

Another departure from prior studies of an SGLT2 inhibitor for patients selected primarily for having CKD was that in EMPA-KIDNEY, 20% of patients did not have albuminuria, and for 34%, eGFR at entry was less than 30 mL/min/1.73 m², with all enrolled patients required to have an eGFR at entry of greater than or equal to 20 mL/min/1.73 m². Average eGFR in EMPA-KIDNEY was about 38 mL/min/1.73 m². To be included in the trial, patients were not required to have albuminuria, except those whose eGFR was greater than or equal to 45 mL/min/1.73 m².

In DAPA-CKD, the minimum eGFR at entry had to be greater than or equal to 25 mL/min/1.73 m², and roughly 14% of enrolled patients had an eGFR of less than 30 mL/min/1.73 m². The average eGFR in DAPA-CKD was about 43 mL/min/1.73 m². In addition, all patients had at least microalbuminuria, with a minimum urinary albumin-to-creatinine ratio of 200. In CREDENCE, the minimum eGFR for enrollment was 30 mL/min/1.73 m², and the average eGFR was about 56 mL/min/1.73 m². All patients in CREDENCE had to have macroalbuminuria, with a urinary albumin-to-creatinine ratio of more than 300.

According to the researchers who designed EMPA-KIDNEY, the trial enrollment criteria aimed to include adults with CKD “who are frequently seen in practice but were under-represented in previous SGLT2 inhibitor trials.”

Indications for empagliflozin are expanding

The success of empagliflozin in EMPA-KIDNEY follows its positive results in both the EMPEROR-Reduced and EMPEROR-Preserved trials, which collectively proved the efficacy of the agent for patients with heart failure regardless of their left ventricular ejection fraction and regardless of whether they also had diabetes.

These results led the U.S. Food and Drug Administration to recently expand the labeled indication for empagliflozin to all patients with heart failure. Empagliflozin also has labeled indications for glycemic control in patients with type 2 diabetes and to reduce the risk of cardiovascular death in adults with type 2 diabetes and established cardiovascular disease.

As of today, empagliflozin has no labeled indication for treating patients with CKD. Dapagliflozin received that indication in April 2021, and canagliflozin received an indication for treating patients with type 2 diabetes, diabetic nephropathy, and albuminuria in September 2019.

EMPA-KIDNEY is sponsored by Boehringer Ingelheim and Lilly, the two companies that jointly market empagliflozin (Jardiance).

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