Cardiology

Compared with separate medications in patients with a prior myocardial infarction, a single pill containing aspirin, a lipid-lowering agent, and an ACE inhibitor provided progressively greater protection from a second cardiovascular (CV) event over the course of a trial with several years of follow-up, according to results of a multinational trial.

“The curves began to separate at the very beginning of the trial, and they are continuing to separate, so we can begin to project the possibility that the results would be even more striking if we had an even longer follow-up,” said Valentin Fuster, MD, physician in chief, Mount Sinai Hospital, New York, who presented the results at the annual congress of the European Society of Cardiology.

MDedge News/Mitchel L. Zoler

By “striking,” Dr. Fuster was referring to a 24% reduction in the hazard ratio of major adverse CV events (MACE) for a trial in which patients were followed for a median of 3 years. The primary composite endpoint consisted of cardiovascular death, MI, stroke, and urgent revascularization (HR, 0.76; P = .02).

AS for the secondary composite endpoint, confined to CV death, MI, and stroke, use of the polypill linked to an even greater relative advantage over usual care (HR, 0.70; P = .005).
 

SECURE trial is latest test of polypill concept

A polypill strategy has been pursued for more than 15 years, according to Dr. Fuster. Other polypill studies have also generated positive results, but the latest trial, called SECURE, is the largest prospective randomized trial to evaluate a single pill combining multiple therapies for secondary prevention.

The degree of relative benefit has “huge implications for clinical care,” reported the ESC-invited commentator, Louise Bowman, MBBS, MD, professor of medicine and clinical trials, University of Oxford (England). She called the findings “in line with what was expected,” but she agreed that the results will drive practice change.

The SECURE trial, published online in the New England Journal of Medicine at the time of its presentation at the ESC congress, randomized 2,499 patients over the age of 65 years who had a MI within the previous 6 months and at least one other risk factor, such as diabetes mellitus, kidney dysfunction, or a prior coronary revascularization. They were enrolled at 113 participating study centers in seven European countries.

Multiple polypill versions permit dose titration

The polypill consisted of aspirin in a fixed dose of 100 mg, the HMG CoA reductase inhibitor atorvastatin, and the ACE inhibitor ramipril. For atorvastatin and ramipril, the target doses were 40 mg and 10 mg, respectively, but different versions of the polypill were available to permit titration to a tolerated dose. Usual care was provided by participating investigators according to ESC recommendations.

The average age of those enrolled was 76 years. Nearly one-third (31%) were women. At baseline, most had hypertension (77.9%), and the majority had diabetes (57.4%).

When the events in the primary endpoint were assessed individually, the polypill was associated with a 33% relative reduction in the risk of CV death (HR, 0.67; P = .03). The reductions in the risk of nonfatal MI (HR, 0.71) and stroke (HR, 0.70) were of the same general magnitude although they did not reach statistical significance. There was no meaningful reduction in urgent revascularization (HR, 0.96).

In addition, the reduction in all-cause mortality (HR, 0.97) was not significant.

The rate of adverse events over the course of the study was 32.7% in the polypill group and 31.6% in the usual-care group, which did not differ significantly. There was also no difference in types of adverse events, including bleeding and other adverse events of interest, according to Dr. Fuster.

Adherence, which was monitored at 6 and 24 months using the Morisky Medication Adherence Scale, was characterized as low, medium, or high. More patients in the polypill group reached high adherence at 6 months (70.6% vs. 62.7%) and at 24 months (74.1% vs. 63.2%). Conversely, fewer patients in the polypill group were deemed to have low adherence at both time points.

“Probably, adherence is the most important reason of how this works,” Dr. Fuster said. Although there were no substantial differences in lipid levels or in systolic or diastolic blood pressure between the two groups when compared at 24 months, there are several theories that might explain the lower event rates in the polypill group, including a more sustained anti-inflammatory effect from greater adherence.

One potential limitation was the open-label design, but Dr. Bowman said that this was unavoidable, given the difficulty of blinding and the fact that comparing a single pill with multiple pills was “the point of the study.” She noted that the 14% withdrawal rate over the course of the trial, which was attributed largely to the COVID-19 pandemic, and the lower than planned enrollment (2,500 vs. a projected 3,000 patients) are also limitations, prohibiting “a more robust result,” but she did not dispute the conclusions.

Polypill benefit documented in all subgroups

While acknowledging these limitations, Dr. Fuster emphasized the consistency of these results with prior polypill studies and within the study. Of the 16 predefined subgroups, such as those created with stratifications for age, sex, comorbidities, and country of treatment, all benefited to a similar degree.

“This really validates the importance of the study,” Dr. Fuster said.

In addition to the implications for risk management globally, Dr. Fuster and others, including Dr. Bowman, spoke of the potential of a relatively inexpensive polypill to improve care in resource-limited settings. Despite the move toward greater personalization of medicine, Dr. Fuster called “simplicity the key to global health” initiatives.

American Heart Association

Salim Yusuf, MD, DPhil, a leader in international polypill research, agreed. He believes the supportive data for this approach are conclusive.

“There are four positive trials of the polypill now and collectively the data are overwhelmingly clear,” Dr. Yusuf, professor of medicine, McMaster University, Hamilton, Ont., said in an interview. “The polypill should be considered in secondary prevention as well as in primary prevention for high-risk individuals. We have estimated that, if it is used in even 50% of those who should get it, it would avoid 2 million premature deaths from CV disease and 6 million nonfatal events. The next step is to implement the findings.”

Dr. Fuster, Dr. Bowman, and Dr. Yusuf reported no potential conflicts of interest.

Compared with separate medications in patients with a prior myocardial infarction, a single pill containing aspirin, a lipid-lowering agent, and an ACE inhibitor provided progressively greater protection from a second cardiovascular (CV) event over the course of a trial with several years of follow-up, according to results of a multinational trial.

“The curves began to separate at the very beginning of the trial, and they are continuing to separate, so we can begin to project the possibility that the results would be even more striking if we had an even longer follow-up,” said Valentin Fuster, MD, physician in chief, Mount Sinai Hospital, New York, who presented the results at the annual congress of the European Society of Cardiology.

MDedge News/Mitchel L. Zoler

By “striking,” Dr. Fuster was referring to a 24% reduction in the hazard ratio of major adverse CV events (MACE) for a trial in which patients were followed for a median of 3 years. The primary composite endpoint consisted of cardiovascular death, MI, stroke, and urgent revascularization (HR, 0.76; P = .02).

AS for the secondary composite endpoint, confined to CV death, MI, and stroke, use of the polypill linked to an even greater relative advantage over usual care (HR, 0.70; P = .005).
 

SECURE trial is latest test of polypill concept

A polypill strategy has been pursued for more than 15 years, according to Dr. Fuster. Other polypill studies have also generated positive results, but the latest trial, called SECURE, is the largest prospective randomized trial to evaluate a single pill combining multiple therapies for secondary prevention.

The degree of relative benefit has “huge implications for clinical care,” reported the ESC-invited commentator, Louise Bowman, MBBS, MD, professor of medicine and clinical trials, University of Oxford (England). She called the findings “in line with what was expected,” but she agreed that the results will drive practice change.

The SECURE trial, published online in the New England Journal of Medicine at the time of its presentation at the ESC congress, randomized 2,499 patients over the age of 65 years who had a MI within the previous 6 months and at least one other risk factor, such as diabetes mellitus, kidney dysfunction, or a prior coronary revascularization. They were enrolled at 113 participating study centers in seven European countries.

Multiple polypill versions permit dose titration

The polypill consisted of aspirin in a fixed dose of 100 mg, the HMG CoA reductase inhibitor atorvastatin, and the ACE inhibitor ramipril. For atorvastatin and ramipril, the target doses were 40 mg and 10 mg, respectively, but different versions of the polypill were available to permit titration to a tolerated dose. Usual care was provided by participating investigators according to ESC recommendations.

The average age of those enrolled was 76 years. Nearly one-third (31%) were women. At baseline, most had hypertension (77.9%), and the majority had diabetes (57.4%).

When the events in the primary endpoint were assessed individually, the polypill was associated with a 33% relative reduction in the risk of CV death (HR, 0.67; P = .03). The reductions in the risk of nonfatal MI (HR, 0.71) and stroke (HR, 0.70) were of the same general magnitude although they did not reach statistical significance. There was no meaningful reduction in urgent revascularization (HR, 0.96).

In addition, the reduction in all-cause mortality (HR, 0.97) was not significant.

The rate of adverse events over the course of the study was 32.7% in the polypill group and 31.6% in the usual-care group, which did not differ significantly. There was also no difference in types of adverse events, including bleeding and other adverse events of interest, according to Dr. Fuster.

Adherence, which was monitored at 6 and 24 months using the Morisky Medication Adherence Scale, was characterized as low, medium, or high. More patients in the polypill group reached high adherence at 6 months (70.6% vs. 62.7%) and at 24 months (74.1% vs. 63.2%). Conversely, fewer patients in the polypill group were deemed to have low adherence at both time points.

“Probably, adherence is the most important reason of how this works,” Dr. Fuster said. Although there were no substantial differences in lipid levels or in systolic or diastolic blood pressure between the two groups when compared at 24 months, there are several theories that might explain the lower event rates in the polypill group, including a more sustained anti-inflammatory effect from greater adherence.

One potential limitation was the open-label design, but Dr. Bowman said that this was unavoidable, given the difficulty of blinding and the fact that comparing a single pill with multiple pills was “the point of the study.” She noted that the 14% withdrawal rate over the course of the trial, which was attributed largely to the COVID-19 pandemic, and the lower than planned enrollment (2,500 vs. a projected 3,000 patients) are also limitations, prohibiting “a more robust result,” but she did not dispute the conclusions.

Polypill benefit documented in all subgroups

While acknowledging these limitations, Dr. Fuster emphasized the consistency of these results with prior polypill studies and within the study. Of the 16 predefined subgroups, such as those created with stratifications for age, sex, comorbidities, and country of treatment, all benefited to a similar degree.

“This really validates the importance of the study,” Dr. Fuster said.

In addition to the implications for risk management globally, Dr. Fuster and others, including Dr. Bowman, spoke of the potential of a relatively inexpensive polypill to improve care in resource-limited settings. Despite the move toward greater personalization of medicine, Dr. Fuster called “simplicity the key to global health” initiatives.

American Heart Association

Salim Yusuf, MD, DPhil, a leader in international polypill research, agreed. He believes the supportive data for this approach are conclusive.

“There are four positive trials of the polypill now and collectively the data are overwhelmingly clear,” Dr. Yusuf, professor of medicine, McMaster University, Hamilton, Ont., said in an interview. “The polypill should be considered in secondary prevention as well as in primary prevention for high-risk individuals. We have estimated that, if it is used in even 50% of those who should get it, it would avoid 2 million premature deaths from CV disease and 6 million nonfatal events. The next step is to implement the findings.”

Dr. Fuster, Dr. Bowman, and Dr. Yusuf reported no potential conflicts of interest.

Compared with separate medications in patients with a prior myocardial infarction, a single pill containing aspirin, a lipid-lowering agent, and an ACE inhibitor provided progressively greater protection from a second cardiovascular (CV) event over the course of a trial with several years of follow-up, according to results of a multinational trial.

“The curves began to separate at the very beginning of the trial, and they are continuing to separate, so we can begin to project the possibility that the results would be even more striking if we had an even longer follow-up,” said Valentin Fuster, MD, physician in chief, Mount Sinai Hospital, New York, who presented the results at the annual congress of the European Society of Cardiology.

MDedge News/Mitchel L. Zoler

By “striking,” Dr. Fuster was referring to a 24% reduction in the hazard ratio of major adverse CV events (MACE) for a trial in which patients were followed for a median of 3 years. The primary composite endpoint consisted of cardiovascular death, MI, stroke, and urgent revascularization (HR, 0.76; P = .02).

AS for the secondary composite endpoint, confined to CV death, MI, and stroke, use of the polypill linked to an even greater relative advantage over usual care (HR, 0.70; P = .005).
 

SECURE trial is latest test of polypill concept

A polypill strategy has been pursued for more than 15 years, according to Dr. Fuster. Other polypill studies have also generated positive results, but the latest trial, called SECURE, is the largest prospective randomized trial to evaluate a single pill combining multiple therapies for secondary prevention.

The degree of relative benefit has “huge implications for clinical care,” reported the ESC-invited commentator, Louise Bowman, MBBS, MD, professor of medicine and clinical trials, University of Oxford (England). She called the findings “in line with what was expected,” but she agreed that the results will drive practice change.

The SECURE trial, published online in the New England Journal of Medicine at the time of its presentation at the ESC congress, randomized 2,499 patients over the age of 65 years who had a MI within the previous 6 months and at least one other risk factor, such as diabetes mellitus, kidney dysfunction, or a prior coronary revascularization. They were enrolled at 113 participating study centers in seven European countries.

Multiple polypill versions permit dose titration

The polypill consisted of aspirin in a fixed dose of 100 mg, the HMG CoA reductase inhibitor atorvastatin, and the ACE inhibitor ramipril. For atorvastatin and ramipril, the target doses were 40 mg and 10 mg, respectively, but different versions of the polypill were available to permit titration to a tolerated dose. Usual care was provided by participating investigators according to ESC recommendations.

The average age of those enrolled was 76 years. Nearly one-third (31%) were women. At baseline, most had hypertension (77.9%), and the majority had diabetes (57.4%).

When the events in the primary endpoint were assessed individually, the polypill was associated with a 33% relative reduction in the risk of CV death (HR, 0.67; P = .03). The reductions in the risk of nonfatal MI (HR, 0.71) and stroke (HR, 0.70) were of the same general magnitude although they did not reach statistical significance. There was no meaningful reduction in urgent revascularization (HR, 0.96).

In addition, the reduction in all-cause mortality (HR, 0.97) was not significant.

The rate of adverse events over the course of the study was 32.7% in the polypill group and 31.6% in the usual-care group, which did not differ significantly. There was also no difference in types of adverse events, including bleeding and other adverse events of interest, according to Dr. Fuster.

Adherence, which was monitored at 6 and 24 months using the Morisky Medication Adherence Scale, was characterized as low, medium, or high. More patients in the polypill group reached high adherence at 6 months (70.6% vs. 62.7%) and at 24 months (74.1% vs. 63.2%). Conversely, fewer patients in the polypill group were deemed to have low adherence at both time points.

“Probably, adherence is the most important reason of how this works,” Dr. Fuster said. Although there were no substantial differences in lipid levels or in systolic or diastolic blood pressure between the two groups when compared at 24 months, there are several theories that might explain the lower event rates in the polypill group, including a more sustained anti-inflammatory effect from greater adherence.

One potential limitation was the open-label design, but Dr. Bowman said that this was unavoidable, given the difficulty of blinding and the fact that comparing a single pill with multiple pills was “the point of the study.” She noted that the 14% withdrawal rate over the course of the trial, which was attributed largely to the COVID-19 pandemic, and the lower than planned enrollment (2,500 vs. a projected 3,000 patients) are also limitations, prohibiting “a more robust result,” but she did not dispute the conclusions.

Polypill benefit documented in all subgroups

While acknowledging these limitations, Dr. Fuster emphasized the consistency of these results with prior polypill studies and within the study. Of the 16 predefined subgroups, such as those created with stratifications for age, sex, comorbidities, and country of treatment, all benefited to a similar degree.

“This really validates the importance of the study,” Dr. Fuster said.

In addition to the implications for risk management globally, Dr. Fuster and others, including Dr. Bowman, spoke of the potential of a relatively inexpensive polypill to improve care in resource-limited settings. Despite the move toward greater personalization of medicine, Dr. Fuster called “simplicity the key to global health” initiatives.

American Heart Association

Salim Yusuf, MD, DPhil, a leader in international polypill research, agreed. He believes the supportive data for this approach are conclusive.

“There are four positive trials of the polypill now and collectively the data are overwhelmingly clear,” Dr. Yusuf, professor of medicine, McMaster University, Hamilton, Ont., said in an interview. “The polypill should be considered in secondary prevention as well as in primary prevention for high-risk individuals. We have estimated that, if it is used in even 50% of those who should get it, it would avoid 2 million premature deaths from CV disease and 6 million nonfatal events. The next step is to implement the findings.”

Dr. Fuster, Dr. Bowman, and Dr. Yusuf reported no potential conflicts of interest.

The wife of a Northern California congressman died late in 2021 after ingesting a plant that is generally considered safe and is used as an herbal remedy for a variety of ailments, including diabetes, obesity, and high cholesterol.

Lori McClintock, the wife of U.S. Rep. Tom McClintock, died from dehydration due to gastroenteritis – an inflammation of the stomach and intestines – that was caused by “adverse effects of white mulberry leaf ingestion,” according to a report from the Sacramento County coroner that is dated March 10 but was not immediately released to the public. KHN obtained that report – in addition to the autopsy report and an amended death certificate containing an updated cause of death – in July.

The coroner’s office ruled her death an accident. The original death certificate, dated Dec. 20, 2021, listed the cause of death as “pending.”

Tom McClintock, a Republican who represents a district that spans multiple counties in northern and central California, found his 61-year-old wife unresponsive at their Elk Grove, Calif., home on Dec. 15, 2021, according to the coroner’s report. He had just returned from Washington after voting in Congress the night before.

It’s unclear from the autopsy report whether Lori McClintock took a dietary supplement containing white mulberry leaf, ate fresh or dried leaves, or drank them in a tea, but a “partially intact” white mulberry leaf was found in her stomach, according to the report.

Ms. McClintock’s death underscores the risks of the vast, booming market of dietary supplements and herbal remedies, which have grown into a $54 billion industry in the United States – one that both lawmakers and health care experts say needs more government scrutiny.

“Many people assume if that product is sold in the United States of America, somebody has inspected it, and it must be safe. Unfortunately, that’s not always true,” U.S. Sen. Richard Durbin (D-Ill.) said on the Senate floor this spring when he introduced legislation to strengthen oversight of dietary supplements.

Daniel Fabricant, CEO and president of the Natural Products Association, which represents the dietary supplements industry, questioned whether Ms. McClintock’s death was related to a supplement.

“It’s completely speculative. There’s a science to this. It’s not just what a coroner feels,” said Mr. Fabricant, who oversaw dietary supplements at the Food and Drug Administration during the Obama administration. “People unfortunately pass from dehydration every day, and there’s a lot of different reasons and a lot of different causes.”

Mr. Fabricant said it would have been ideal had the coroner or the family reported her death to the FDA so the agency could have launched an investigation.

Such reports are voluntary, and it’s not clear whether anyone reported her death to the agency. FDA spokesperson Courtney Rhodes said the agency does not discuss possible or ongoing investigations.

The FDA, Mr. Fabricant added, has a system in place to investigate deaths that might be linked to a supplement or drug. “It’s casework,” he said. “It’s good, old-fashioned police work that needs to be done.”

Tom McClintock has remained mostly silent about his wife’s death since he released a statement on Dec. 19, 2021, announcing it and gave a tribute to her at her Jan. 4 funeral. Until now, the cause of death had not been reported.

Mr. McClintock, contacted multiple times by phone and email Wednesday, was not immediately available for comment.

At his wife’s funeral, McClintock told mourners that she was fine when he spoke with her the day before he returned. She had told a friend that “she was on a roll” at a new job she loved in a Sacramento real estate office, he said, and “she was carefully dieting.”

“She just joined a gym,” he said. “At home, she was counting down the days to Christmas, wrapping all the gifts and making all the plans to make it the best family Christmas ever, and it would have been.”

According to the coroner’s report, however, the day before her death, “she had complaints of an upset stomach.”

Sacramento County spokesperson Kim Nava said via email Wednesday that the law prohibits the coroner’s office from discussing many details of specific cases. As part of any death investigation, the office “attempts to locate and review medical records and speak to family/witnesses to establish events leading up to and surrounding a death,” she said.

If any medications or supplements are found at the scene or if pertinent information is in the person’s medical records, those are passed along to the pathologist to help establish cause of death, Ms. Nava said.

“Any information the office obtains from medical records can’t be disseminated to a third party except by court order,” she said.

The leaves and fruit of the white mulberry tree, which is native to China, have been used for centuries in traditional medicine. Academic studies over the past decade have found that the extract from its leaves can lower blood sugar levels and help with weight loss. People take it in capsule or pill form, as an extract or powder. They can also brew the leaves as an herbal tea.

Lori McClintock’s reaction seems unusual. No deaths from the white mulberry plant have been reported to poison control officials in the past 10 years, according to the American Association of Poison Control Centers.

Since 2012, 148 cases of white mulberry plant ingestion were voluntarily reported to poison control officials nationally, most involving accidental ingestion by children 12 and under, said Kaitlyn Brown, clinical managing director for the association. Only one case required medical follow-up, she said.

While poison control centers track exposures to the white mulberry plant, the FDA oversees dietary supplements, such as products that contain white mulberry leaf extract. Since 2004, two cases of people sickened by mulberry supplements have been reported to the FDA, according to its database that tracks “adverse events.” It relies heavily on voluntary reports from health care professionals and consumers. At least one of those cases led to hospitalization.

White mulberry leaf can have side effects, including nausea and diarrhea, according to research. Independent lab tests ordered by the coroner’s office showed Ms. McClintock’s body had elevated levels of nitrogen, sodium, and creatinine – all signs of dehydration, according to three pathologists who reviewed the coroner’s documents, which KHN redacted to remove Ms. McClintock’s name.

White mulberry leaves “do tend to cause dehydration, and part of the uses for that can be to help someone lose weight, mostly through fluid loss, which in this case was just kind of excessive,” said D’Michelle DuPre, MD, a retired forensic pathologist and a former medical examiner in South Carolina who reviewed the documents.

Dietary supplements, which include a broad range of vitamins, herbs, and minerals, are regulated by the FDA. However, they are classified as food and don’t undergo the rigorous scientific and safety testing the government requires of prescription drugs and over-the-counter medicines.

Lawmakers aren’t proposing to put supplements into the same category as pharmaceuticals, but some say they are alarmed that neither the FDA nor the industry knows how many dietary supplements are out there – making it almost impossible for the government to oversee them and punish bad actors.

The FDA estimates 40,000 to 80,000 supplement products are on the market in the United States, and industry surveys estimate 80% of Americans use them.

Legislation by Sen. Durbin and U.S. Sen. Mike Braun (R-Ind.) would require manufacturers to register with the FDA and provide a public list of ingredients in their products, two provisions that are backed by the Council for Responsible Nutrition, another industry group that represents supplement makers.

But the council is lobbying against a provision that would require supplement makers to provide consumers with the ingredient amounts – or the blend – in their products, something they say is akin to giving a recipe to competitors. That’s proprietary information only government regulators should have access to, said Megan Olsen, the group’s senior vice president and general counsel.

Ms. Olsen explained that supplement manufacturers are regulated just like other food companies and are subject to strict labeling requirements and inspections by the FDA. They also must inform the agency about any adverse effects reported by consumers or doctors.

“Companies are testing products throughout the process, are reviewing how they’re being manufactured and what’s going into them,” Ms. Olsen said. “All of that is overseen and dictated by FDA regulation.”

The dietary supplement provisions were rolled into a larger Senate health committee bill that reauthorizes FDA programs, and senators are currently in negotiations with the House of Representatives. The Natural Products Association opposes all of the dietary supplement provisions.

Because dietary pills, teas, and other supplements are regulated as food products, manufacturers can’t advertise them as treatments or cures for health issues. But they can make claims about how the supplements affect the body. So someone who wants to lose weight or get their diabetes under control might reach for a bottle of white mulberry leaf extract because some supplement makers advertise it as a natural remedy that can lower blood sugar levels and promote weight loss.

Those kinds of claims are appealing to Americans and have been especially potent during the pandemic, as people sought to boost their immune systems and fend off COVID-19, said Debbie Petitpain, a registered dietitian nutritionist and a spokesperson for the Academy of Nutrition and Dietetics.

But dietary supplements can be dangerous and don’t affect everyone the same way. Mixing supplements and prescription medicines can compound the problem, according to the FDA.

“I think a lot of people are thinking, ‘Oh, it’s a plant.’ Or, ‘Oh, it’s just a vitamin. Certainly, that means that it’s not going to hurt me,’ ” Ms. Petitpain said. “But there’s always a risk for taking anything.”

It’s not clear why Lori McClintock was taking white mulberry leaf. Friends and family who gathered for her funeral described a vibrant, happy woman who loved her family and her work and already had wrapped Christmas presents under the tree in mid-December. She was planning to buy a recreational vehicle with her husband in retirement.

“We grieve the loss because of all the things she was looking forward to doing and all the years yet ahead,” Tom McClintock told mourners. “And we grieve for something else, because we’ve all lost a genuinely good person in our lives.”
 

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

The wife of a Northern California congressman died late in 2021 after ingesting a plant that is generally considered safe and is used as an herbal remedy for a variety of ailments, including diabetes, obesity, and high cholesterol.

Lori McClintock, the wife of U.S. Rep. Tom McClintock, died from dehydration due to gastroenteritis – an inflammation of the stomach and intestines – that was caused by “adverse effects of white mulberry leaf ingestion,” according to a report from the Sacramento County coroner that is dated March 10 but was not immediately released to the public. KHN obtained that report – in addition to the autopsy report and an amended death certificate containing an updated cause of death – in July.

The coroner’s office ruled her death an accident. The original death certificate, dated Dec. 20, 2021, listed the cause of death as “pending.”

Tom McClintock, a Republican who represents a district that spans multiple counties in northern and central California, found his 61-year-old wife unresponsive at their Elk Grove, Calif., home on Dec. 15, 2021, according to the coroner’s report. He had just returned from Washington after voting in Congress the night before.

It’s unclear from the autopsy report whether Lori McClintock took a dietary supplement containing white mulberry leaf, ate fresh or dried leaves, or drank them in a tea, but a “partially intact” white mulberry leaf was found in her stomach, according to the report.

Ms. McClintock’s death underscores the risks of the vast, booming market of dietary supplements and herbal remedies, which have grown into a $54 billion industry in the United States – one that both lawmakers and health care experts say needs more government scrutiny.

“Many people assume if that product is sold in the United States of America, somebody has inspected it, and it must be safe. Unfortunately, that’s not always true,” U.S. Sen. Richard Durbin (D-Ill.) said on the Senate floor this spring when he introduced legislation to strengthen oversight of dietary supplements.

Daniel Fabricant, CEO and president of the Natural Products Association, which represents the dietary supplements industry, questioned whether Ms. McClintock’s death was related to a supplement.

“It’s completely speculative. There’s a science to this. It’s not just what a coroner feels,” said Mr. Fabricant, who oversaw dietary supplements at the Food and Drug Administration during the Obama administration. “People unfortunately pass from dehydration every day, and there’s a lot of different reasons and a lot of different causes.”

Mr. Fabricant said it would have been ideal had the coroner or the family reported her death to the FDA so the agency could have launched an investigation.

Such reports are voluntary, and it’s not clear whether anyone reported her death to the agency. FDA spokesperson Courtney Rhodes said the agency does not discuss possible or ongoing investigations.

The FDA, Mr. Fabricant added, has a system in place to investigate deaths that might be linked to a supplement or drug. “It’s casework,” he said. “It’s good, old-fashioned police work that needs to be done.”

Tom McClintock has remained mostly silent about his wife’s death since he released a statement on Dec. 19, 2021, announcing it and gave a tribute to her at her Jan. 4 funeral. Until now, the cause of death had not been reported.

Mr. McClintock, contacted multiple times by phone and email Wednesday, was not immediately available for comment.

At his wife’s funeral, McClintock told mourners that she was fine when he spoke with her the day before he returned. She had told a friend that “she was on a roll” at a new job she loved in a Sacramento real estate office, he said, and “she was carefully dieting.”

“She just joined a gym,” he said. “At home, she was counting down the days to Christmas, wrapping all the gifts and making all the plans to make it the best family Christmas ever, and it would have been.”

According to the coroner’s report, however, the day before her death, “she had complaints of an upset stomach.”

Sacramento County spokesperson Kim Nava said via email Wednesday that the law prohibits the coroner’s office from discussing many details of specific cases. As part of any death investigation, the office “attempts to locate and review medical records and speak to family/witnesses to establish events leading up to and surrounding a death,” she said.

If any medications or supplements are found at the scene or if pertinent information is in the person’s medical records, those are passed along to the pathologist to help establish cause of death, Ms. Nava said.

“Any information the office obtains from medical records can’t be disseminated to a third party except by court order,” she said.

The leaves and fruit of the white mulberry tree, which is native to China, have been used for centuries in traditional medicine. Academic studies over the past decade have found that the extract from its leaves can lower blood sugar levels and help with weight loss. People take it in capsule or pill form, as an extract or powder. They can also brew the leaves as an herbal tea.

Lori McClintock’s reaction seems unusual. No deaths from the white mulberry plant have been reported to poison control officials in the past 10 years, according to the American Association of Poison Control Centers.

Since 2012, 148 cases of white mulberry plant ingestion were voluntarily reported to poison control officials nationally, most involving accidental ingestion by children 12 and under, said Kaitlyn Brown, clinical managing director for the association. Only one case required medical follow-up, she said.

While poison control centers track exposures to the white mulberry plant, the FDA oversees dietary supplements, such as products that contain white mulberry leaf extract. Since 2004, two cases of people sickened by mulberry supplements have been reported to the FDA, according to its database that tracks “adverse events.” It relies heavily on voluntary reports from health care professionals and consumers. At least one of those cases led to hospitalization.

White mulberry leaf can have side effects, including nausea and diarrhea, according to research. Independent lab tests ordered by the coroner’s office showed Ms. McClintock’s body had elevated levels of nitrogen, sodium, and creatinine – all signs of dehydration, according to three pathologists who reviewed the coroner’s documents, which KHN redacted to remove Ms. McClintock’s name.

White mulberry leaves “do tend to cause dehydration, and part of the uses for that can be to help someone lose weight, mostly through fluid loss, which in this case was just kind of excessive,” said D’Michelle DuPre, MD, a retired forensic pathologist and a former medical examiner in South Carolina who reviewed the documents.

Dietary supplements, which include a broad range of vitamins, herbs, and minerals, are regulated by the FDA. However, they are classified as food and don’t undergo the rigorous scientific and safety testing the government requires of prescription drugs and over-the-counter medicines.

Lawmakers aren’t proposing to put supplements into the same category as pharmaceuticals, but some say they are alarmed that neither the FDA nor the industry knows how many dietary supplements are out there – making it almost impossible for the government to oversee them and punish bad actors.

The FDA estimates 40,000 to 80,000 supplement products are on the market in the United States, and industry surveys estimate 80% of Americans use them.

Legislation by Sen. Durbin and U.S. Sen. Mike Braun (R-Ind.) would require manufacturers to register with the FDA and provide a public list of ingredients in their products, two provisions that are backed by the Council for Responsible Nutrition, another industry group that represents supplement makers.

But the council is lobbying against a provision that would require supplement makers to provide consumers with the ingredient amounts – or the blend – in their products, something they say is akin to giving a recipe to competitors. That’s proprietary information only government regulators should have access to, said Megan Olsen, the group’s senior vice president and general counsel.

Ms. Olsen explained that supplement manufacturers are regulated just like other food companies and are subject to strict labeling requirements and inspections by the FDA. They also must inform the agency about any adverse effects reported by consumers or doctors.

“Companies are testing products throughout the process, are reviewing how they’re being manufactured and what’s going into them,” Ms. Olsen said. “All of that is overseen and dictated by FDA regulation.”

The dietary supplement provisions were rolled into a larger Senate health committee bill that reauthorizes FDA programs, and senators are currently in negotiations with the House of Representatives. The Natural Products Association opposes all of the dietary supplement provisions.

Because dietary pills, teas, and other supplements are regulated as food products, manufacturers can’t advertise them as treatments or cures for health issues. But they can make claims about how the supplements affect the body. So someone who wants to lose weight or get their diabetes under control might reach for a bottle of white mulberry leaf extract because some supplement makers advertise it as a natural remedy that can lower blood sugar levels and promote weight loss.

Those kinds of claims are appealing to Americans and have been especially potent during the pandemic, as people sought to boost their immune systems and fend off COVID-19, said Debbie Petitpain, a registered dietitian nutritionist and a spokesperson for the Academy of Nutrition and Dietetics.

But dietary supplements can be dangerous and don’t affect everyone the same way. Mixing supplements and prescription medicines can compound the problem, according to the FDA.

“I think a lot of people are thinking, ‘Oh, it’s a plant.’ Or, ‘Oh, it’s just a vitamin. Certainly, that means that it’s not going to hurt me,’ ” Ms. Petitpain said. “But there’s always a risk for taking anything.”

It’s not clear why Lori McClintock was taking white mulberry leaf. Friends and family who gathered for her funeral described a vibrant, happy woman who loved her family and her work and already had wrapped Christmas presents under the tree in mid-December. She was planning to buy a recreational vehicle with her husband in retirement.

“We grieve the loss because of all the things she was looking forward to doing and all the years yet ahead,” Tom McClintock told mourners. “And we grieve for something else, because we’ve all lost a genuinely good person in our lives.”
 

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

The wife of a Northern California congressman died late in 2021 after ingesting a plant that is generally considered safe and is used as an herbal remedy for a variety of ailments, including diabetes, obesity, and high cholesterol.

Lori McClintock, the wife of U.S. Rep. Tom McClintock, died from dehydration due to gastroenteritis – an inflammation of the stomach and intestines – that was caused by “adverse effects of white mulberry leaf ingestion,” according to a report from the Sacramento County coroner that is dated March 10 but was not immediately released to the public. KHN obtained that report – in addition to the autopsy report and an amended death certificate containing an updated cause of death – in July.

The coroner’s office ruled her death an accident. The original death certificate, dated Dec. 20, 2021, listed the cause of death as “pending.”

Tom McClintock, a Republican who represents a district that spans multiple counties in northern and central California, found his 61-year-old wife unresponsive at their Elk Grove, Calif., home on Dec. 15, 2021, according to the coroner’s report. He had just returned from Washington after voting in Congress the night before.

It’s unclear from the autopsy report whether Lori McClintock took a dietary supplement containing white mulberry leaf, ate fresh or dried leaves, or drank them in a tea, but a “partially intact” white mulberry leaf was found in her stomach, according to the report.

Ms. McClintock’s death underscores the risks of the vast, booming market of dietary supplements and herbal remedies, which have grown into a $54 billion industry in the United States – one that both lawmakers and health care experts say needs more government scrutiny.

“Many people assume if that product is sold in the United States of America, somebody has inspected it, and it must be safe. Unfortunately, that’s not always true,” U.S. Sen. Richard Durbin (D-Ill.) said on the Senate floor this spring when he introduced legislation to strengthen oversight of dietary supplements.

Daniel Fabricant, CEO and president of the Natural Products Association, which represents the dietary supplements industry, questioned whether Ms. McClintock’s death was related to a supplement.

“It’s completely speculative. There’s a science to this. It’s not just what a coroner feels,” said Mr. Fabricant, who oversaw dietary supplements at the Food and Drug Administration during the Obama administration. “People unfortunately pass from dehydration every day, and there’s a lot of different reasons and a lot of different causes.”

Mr. Fabricant said it would have been ideal had the coroner or the family reported her death to the FDA so the agency could have launched an investigation.

Such reports are voluntary, and it’s not clear whether anyone reported her death to the agency. FDA spokesperson Courtney Rhodes said the agency does not discuss possible or ongoing investigations.

The FDA, Mr. Fabricant added, has a system in place to investigate deaths that might be linked to a supplement or drug. “It’s casework,” he said. “It’s good, old-fashioned police work that needs to be done.”

Tom McClintock has remained mostly silent about his wife’s death since he released a statement on Dec. 19, 2021, announcing it and gave a tribute to her at her Jan. 4 funeral. Until now, the cause of death had not been reported.

Mr. McClintock, contacted multiple times by phone and email Wednesday, was not immediately available for comment.

At his wife’s funeral, McClintock told mourners that she was fine when he spoke with her the day before he returned. She had told a friend that “she was on a roll” at a new job she loved in a Sacramento real estate office, he said, and “she was carefully dieting.”

“She just joined a gym,” he said. “At home, she was counting down the days to Christmas, wrapping all the gifts and making all the plans to make it the best family Christmas ever, and it would have been.”

According to the coroner’s report, however, the day before her death, “she had complaints of an upset stomach.”

Sacramento County spokesperson Kim Nava said via email Wednesday that the law prohibits the coroner’s office from discussing many details of specific cases. As part of any death investigation, the office “attempts to locate and review medical records and speak to family/witnesses to establish events leading up to and surrounding a death,” she said.

If any medications or supplements are found at the scene or if pertinent information is in the person’s medical records, those are passed along to the pathologist to help establish cause of death, Ms. Nava said.

“Any information the office obtains from medical records can’t be disseminated to a third party except by court order,” she said.

The leaves and fruit of the white mulberry tree, which is native to China, have been used for centuries in traditional medicine. Academic studies over the past decade have found that the extract from its leaves can lower blood sugar levels and help with weight loss. People take it in capsule or pill form, as an extract or powder. They can also brew the leaves as an herbal tea.

Lori McClintock’s reaction seems unusual. No deaths from the white mulberry plant have been reported to poison control officials in the past 10 years, according to the American Association of Poison Control Centers.

Since 2012, 148 cases of white mulberry plant ingestion were voluntarily reported to poison control officials nationally, most involving accidental ingestion by children 12 and under, said Kaitlyn Brown, clinical managing director for the association. Only one case required medical follow-up, she said.

While poison control centers track exposures to the white mulberry plant, the FDA oversees dietary supplements, such as products that contain white mulberry leaf extract. Since 2004, two cases of people sickened by mulberry supplements have been reported to the FDA, according to its database that tracks “adverse events.” It relies heavily on voluntary reports from health care professionals and consumers. At least one of those cases led to hospitalization.

White mulberry leaf can have side effects, including nausea and diarrhea, according to research. Independent lab tests ordered by the coroner’s office showed Ms. McClintock’s body had elevated levels of nitrogen, sodium, and creatinine – all signs of dehydration, according to three pathologists who reviewed the coroner’s documents, which KHN redacted to remove Ms. McClintock’s name.

White mulberry leaves “do tend to cause dehydration, and part of the uses for that can be to help someone lose weight, mostly through fluid loss, which in this case was just kind of excessive,” said D’Michelle DuPre, MD, a retired forensic pathologist and a former medical examiner in South Carolina who reviewed the documents.

Dietary supplements, which include a broad range of vitamins, herbs, and minerals, are regulated by the FDA. However, they are classified as food and don’t undergo the rigorous scientific and safety testing the government requires of prescription drugs and over-the-counter medicines.

Lawmakers aren’t proposing to put supplements into the same category as pharmaceuticals, but some say they are alarmed that neither the FDA nor the industry knows how many dietary supplements are out there – making it almost impossible for the government to oversee them and punish bad actors.

The FDA estimates 40,000 to 80,000 supplement products are on the market in the United States, and industry surveys estimate 80% of Americans use them.

Legislation by Sen. Durbin and U.S. Sen. Mike Braun (R-Ind.) would require manufacturers to register with the FDA and provide a public list of ingredients in their products, two provisions that are backed by the Council for Responsible Nutrition, another industry group that represents supplement makers.

But the council is lobbying against a provision that would require supplement makers to provide consumers with the ingredient amounts – or the blend – in their products, something they say is akin to giving a recipe to competitors. That’s proprietary information only government regulators should have access to, said Megan Olsen, the group’s senior vice president and general counsel.

Ms. Olsen explained that supplement manufacturers are regulated just like other food companies and are subject to strict labeling requirements and inspections by the FDA. They also must inform the agency about any adverse effects reported by consumers or doctors.

“Companies are testing products throughout the process, are reviewing how they’re being manufactured and what’s going into them,” Ms. Olsen said. “All of that is overseen and dictated by FDA regulation.”

The dietary supplement provisions were rolled into a larger Senate health committee bill that reauthorizes FDA programs, and senators are currently in negotiations with the House of Representatives. The Natural Products Association opposes all of the dietary supplement provisions.

Because dietary pills, teas, and other supplements are regulated as food products, manufacturers can’t advertise them as treatments or cures for health issues. But they can make claims about how the supplements affect the body. So someone who wants to lose weight or get their diabetes under control might reach for a bottle of white mulberry leaf extract because some supplement makers advertise it as a natural remedy that can lower blood sugar levels and promote weight loss.

Those kinds of claims are appealing to Americans and have been especially potent during the pandemic, as people sought to boost their immune systems and fend off COVID-19, said Debbie Petitpain, a registered dietitian nutritionist and a spokesperson for the Academy of Nutrition and Dietetics.

But dietary supplements can be dangerous and don’t affect everyone the same way. Mixing supplements and prescription medicines can compound the problem, according to the FDA.

“I think a lot of people are thinking, ‘Oh, it’s a plant.’ Or, ‘Oh, it’s just a vitamin. Certainly, that means that it’s not going to hurt me,’ ” Ms. Petitpain said. “But there’s always a risk for taking anything.”

It’s not clear why Lori McClintock was taking white mulberry leaf. Friends and family who gathered for her funeral described a vibrant, happy woman who loved her family and her work and already had wrapped Christmas presents under the tree in mid-December. She was planning to buy a recreational vehicle with her husband in retirement.

“We grieve the loss because of all the things she was looking forward to doing and all the years yet ahead,” Tom McClintock told mourners. “And we grieve for something else, because we’ve all lost a genuinely good person in our lives.”
 

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

SEOUL, South Korea – Menopause before age 40 is associated with elevated risk of heart failure and atrial fibrillation, according to a study published in European Heart Journal, from the European Society of Cardiology (ESC). The study of more than 1.4 million women revealed that the younger the age at menopause, the higher the risk of heart failure and atrial fibrillation.

“Women with premature menopause should be aware that they may be more likely to develop heart failure or atrial fibrillation than their peers,” said study author Ga Eun Nam, MD, PhD, of Korea University College of Medicine, Seoul. “This may be good motivation to improve lifestyle habits known to be linked with heart disease, such as quitting smoking and exercising.”

Cardiovascular disease typically occurs up to 10 years later in women than men. Premenopausal women are thought to benefit from estrogen’s protective effect on the cardiovascular system. The cessation of menstruation and subsequent decline of estrogen levels may make women more vulnerable to cardiovascular disease.
 

A national population

Premature menopause affects 1% of women younger than 40 years, the ESC press release stated. Prior studies have found a link between premature (before age 40 years) and early (before age 45 years) menopause and cardiovascular disease overall, but the evidence for heart failure or atrial fibrillation alone is limited. This study examined the associations between premature menopause, age at menopause, and incident heart failure and atrial fibrillation. Data were obtained from the Korean National Health Insurance System (NHIS), which provides health screening at least every 2 years and includes 97% of the population.

The study included 1,401,175 postmenopausal women aged 30 years and older who completed the NHIS health checkup in 2009. Participants were monitored until the end of 2018 for new-onset heart failure and atrial fibrillation. Information was collected on demographics, health behaviors, and reproductive factors, including age at menopause and use of hormone replacement therapy (HRT). Age at menopause was split into four categories: younger than 40 years, 40-44 years, 45-49 years, and 50 years or older. Premature menopause was defined as having the final menstrual period before age 40 years.

Some 28,111 (2%) participants had a history of premature menopause. For these women, the average age at menopause was 36.7 years. The average age at study enrollment for women with and for those without a history of premature menopause was 60 and 61.5 years, respectively. During an average follow-up of 9.1 years, 42,699 (3.0%) developed heart failure, and 44,834 (3.2%) developed atrial fibrillation.

The researchers analyzed the association between history of premature menopause and incident heart failure and atrial fibrillation after adjusting for age, smoking, alcohol use, physical activity, income, body mass index, hypertension, type 2 diabetes, dyslipidemia, chronic kidney disease, coronary heart disease, HRT, and age at menarche. Women who experienced premature menopause had a 33% higher risk for heart failure and 9% higher risk for atrial fibrillation, compared with those who did not.
 

Reproductive history

The researchers then analyzed the associations between age at menopause and incidence of heart failure and atrial fibrillation after adjusting for the same factors as in the previous analyses. The risk for incident heart failure increased as the age at menopause decreased. Compared with women aged 50 years and older at menopause, those aged 45-49 years, 40-44 years, and younger than 40 years at menopause had 11%, 23%, and 39% greater risk for incident heart failure, respectively. Similarly, the risk for incident atrial fibrillation increased as the age at menopause decreased; the risk was 4%, 10%, and 11% higher for those aged 45-49 years, 40-44 years, and younger than 40 years at menopause, respectively, compared with women aged 50 years and older at menopause.

The authors said that several factors may explain the associations between menopausal age, heart failure, and atrial fibrillation, such as the drop in estrogen levels and changes in body fat distribution.

Dr. Nam concluded, “The misconception that heart disease primarily affects men has meant that sex-specific risk factors have been largely ignored. Evidence is growing that undergoing menopause before the age of 40 years may increase the likelihood of heart disease later in life. Our study indicates that reproductive history should be routinely considered in addition to traditional risk factors such as smoking when evaluating the future likelihood of heart failure and atrial fibrillation.”

A version of this article appeared on Medscape.com. This article was translated from the Medscape French edition.

SEOUL, South Korea – Menopause before age 40 is associated with elevated risk of heart failure and atrial fibrillation, according to a study published in European Heart Journal, from the European Society of Cardiology (ESC). The study of more than 1.4 million women revealed that the younger the age at menopause, the higher the risk of heart failure and atrial fibrillation.

“Women with premature menopause should be aware that they may be more likely to develop heart failure or atrial fibrillation than their peers,” said study author Ga Eun Nam, MD, PhD, of Korea University College of Medicine, Seoul. “This may be good motivation to improve lifestyle habits known to be linked with heart disease, such as quitting smoking and exercising.”

Cardiovascular disease typically occurs up to 10 years later in women than men. Premenopausal women are thought to benefit from estrogen’s protective effect on the cardiovascular system. The cessation of menstruation and subsequent decline of estrogen levels may make women more vulnerable to cardiovascular disease.
 

A national population

Premature menopause affects 1% of women younger than 40 years, the ESC press release stated. Prior studies have found a link between premature (before age 40 years) and early (before age 45 years) menopause and cardiovascular disease overall, but the evidence for heart failure or atrial fibrillation alone is limited. This study examined the associations between premature menopause, age at menopause, and incident heart failure and atrial fibrillation. Data were obtained from the Korean National Health Insurance System (NHIS), which provides health screening at least every 2 years and includes 97% of the population.

The study included 1,401,175 postmenopausal women aged 30 years and older who completed the NHIS health checkup in 2009. Participants were monitored until the end of 2018 for new-onset heart failure and atrial fibrillation. Information was collected on demographics, health behaviors, and reproductive factors, including age at menopause and use of hormone replacement therapy (HRT). Age at menopause was split into four categories: younger than 40 years, 40-44 years, 45-49 years, and 50 years or older. Premature menopause was defined as having the final menstrual period before age 40 years.

Some 28,111 (2%) participants had a history of premature menopause. For these women, the average age at menopause was 36.7 years. The average age at study enrollment for women with and for those without a history of premature menopause was 60 and 61.5 years, respectively. During an average follow-up of 9.1 years, 42,699 (3.0%) developed heart failure, and 44,834 (3.2%) developed atrial fibrillation.

The researchers analyzed the association between history of premature menopause and incident heart failure and atrial fibrillation after adjusting for age, smoking, alcohol use, physical activity, income, body mass index, hypertension, type 2 diabetes, dyslipidemia, chronic kidney disease, coronary heart disease, HRT, and age at menarche. Women who experienced premature menopause had a 33% higher risk for heart failure and 9% higher risk for atrial fibrillation, compared with those who did not.
 

Reproductive history

The researchers then analyzed the associations between age at menopause and incidence of heart failure and atrial fibrillation after adjusting for the same factors as in the previous analyses. The risk for incident heart failure increased as the age at menopause decreased. Compared with women aged 50 years and older at menopause, those aged 45-49 years, 40-44 years, and younger than 40 years at menopause had 11%, 23%, and 39% greater risk for incident heart failure, respectively. Similarly, the risk for incident atrial fibrillation increased as the age at menopause decreased; the risk was 4%, 10%, and 11% higher for those aged 45-49 years, 40-44 years, and younger than 40 years at menopause, respectively, compared with women aged 50 years and older at menopause.

The authors said that several factors may explain the associations between menopausal age, heart failure, and atrial fibrillation, such as the drop in estrogen levels and changes in body fat distribution.

Dr. Nam concluded, “The misconception that heart disease primarily affects men has meant that sex-specific risk factors have been largely ignored. Evidence is growing that undergoing menopause before the age of 40 years may increase the likelihood of heart disease later in life. Our study indicates that reproductive history should be routinely considered in addition to traditional risk factors such as smoking when evaluating the future likelihood of heart failure and atrial fibrillation.”

A version of this article appeared on Medscape.com. This article was translated from the Medscape French edition.

SEOUL, South Korea – Menopause before age 40 is associated with elevated risk of heart failure and atrial fibrillation, according to a study published in European Heart Journal, from the European Society of Cardiology (ESC). The study of more than 1.4 million women revealed that the younger the age at menopause, the higher the risk of heart failure and atrial fibrillation.

“Women with premature menopause should be aware that they may be more likely to develop heart failure or atrial fibrillation than their peers,” said study author Ga Eun Nam, MD, PhD, of Korea University College of Medicine, Seoul. “This may be good motivation to improve lifestyle habits known to be linked with heart disease, such as quitting smoking and exercising.”

Cardiovascular disease typically occurs up to 10 years later in women than men. Premenopausal women are thought to benefit from estrogen’s protective effect on the cardiovascular system. The cessation of menstruation and subsequent decline of estrogen levels may make women more vulnerable to cardiovascular disease.
 

A national population

Premature menopause affects 1% of women younger than 40 years, the ESC press release stated. Prior studies have found a link between premature (before age 40 years) and early (before age 45 years) menopause and cardiovascular disease overall, but the evidence for heart failure or atrial fibrillation alone is limited. This study examined the associations between premature menopause, age at menopause, and incident heart failure and atrial fibrillation. Data were obtained from the Korean National Health Insurance System (NHIS), which provides health screening at least every 2 years and includes 97% of the population.

The study included 1,401,175 postmenopausal women aged 30 years and older who completed the NHIS health checkup in 2009. Participants were monitored until the end of 2018 for new-onset heart failure and atrial fibrillation. Information was collected on demographics, health behaviors, and reproductive factors, including age at menopause and use of hormone replacement therapy (HRT). Age at menopause was split into four categories: younger than 40 years, 40-44 years, 45-49 years, and 50 years or older. Premature menopause was defined as having the final menstrual period before age 40 years.

Some 28,111 (2%) participants had a history of premature menopause. For these women, the average age at menopause was 36.7 years. The average age at study enrollment for women with and for those without a history of premature menopause was 60 and 61.5 years, respectively. During an average follow-up of 9.1 years, 42,699 (3.0%) developed heart failure, and 44,834 (3.2%) developed atrial fibrillation.

The researchers analyzed the association between history of premature menopause and incident heart failure and atrial fibrillation after adjusting for age, smoking, alcohol use, physical activity, income, body mass index, hypertension, type 2 diabetes, dyslipidemia, chronic kidney disease, coronary heart disease, HRT, and age at menarche. Women who experienced premature menopause had a 33% higher risk for heart failure and 9% higher risk for atrial fibrillation, compared with those who did not.
 

Reproductive history

The researchers then analyzed the associations between age at menopause and incidence of heart failure and atrial fibrillation after adjusting for the same factors as in the previous analyses. The risk for incident heart failure increased as the age at menopause decreased. Compared with women aged 50 years and older at menopause, those aged 45-49 years, 40-44 years, and younger than 40 years at menopause had 11%, 23%, and 39% greater risk for incident heart failure, respectively. Similarly, the risk for incident atrial fibrillation increased as the age at menopause decreased; the risk was 4%, 10%, and 11% higher for those aged 45-49 years, 40-44 years, and younger than 40 years at menopause, respectively, compared with women aged 50 years and older at menopause.

The authors said that several factors may explain the associations between menopausal age, heart failure, and atrial fibrillation, such as the drop in estrogen levels and changes in body fat distribution.

Dr. Nam concluded, “The misconception that heart disease primarily affects men has meant that sex-specific risk factors have been largely ignored. Evidence is growing that undergoing menopause before the age of 40 years may increase the likelihood of heart disease later in life. Our study indicates that reproductive history should be routinely considered in addition to traditional risk factors such as smoking when evaluating the future likelihood of heart failure and atrial fibrillation.”

A version of this article appeared on Medscape.com. This article was translated from the Medscape French edition.

People with diabetes who take nonsteroidal anti-inflammatory drugs even on a short-term basis may have about a 50% greater risk of developing heart failure, according to results from a national registry study of more than 330,000 patients to be presented at the annual congress of the European Society of Cardiology.

“According to data from this study, even short-term NSAID use – within 28 days – in patients with type 2 diabetes mellitus are associated with an increased risk of first-time heart failure hospitalization,” lead author Anders Holt, MD, said in an interview.

“Further, it seems that patients above 79 years of age or with elevated hemoglobin A1c levels, along with new users of NSAIDs, are particularly susceptible.” He added that no such association was found in patients below age 65 years with normal A1c levels.

Dr. Holt has a dual appointment as a cardiologist at Copenhagen University and Herlev-Gentofte Hospital in Hellerup, Denmark, and the department of epidemiology and biostatistics at the University of Auckland (New Zealand). Jarl Emmanuel Strange, MD, PhD, a fellow at Copenhagen University, is to present the abstract on Aug. 26.

“This is quite an important observation given that, unfortunately, NSAIDs continue to be prescribed rather easily to people with diabetes and these agents do have risk,” said Rodica Busui, MD, PhD, codirector of the JDRF Center of Excellence at the University of Michigan, Ann Arbor, and president-elect for medicine and science of the American Diabetes Association. Dr. Busui is also lead author of an ADA/American College of Cardiology consensus report on heart failure in diabetes.

The study hypothesized that fluid retention “is a known but underappreciated side effect” of NSAID use and that short-term NSAID use could lead to heart failure in patients with type 2 diabetes, which has been linked to subclinical cardiomyopathy and kidney dysfunction.

“According to this study and particularly the subgroups analyses, it seems that incident heart failure associated with short-term NSAID use could be more than ‘just fluid overload,’ ” Dr. Holt said. “Further investigations into the specific mechanisms causing these associations are warranted.”

The study identified 331,189 patients with type 2 diabetes in nationwide Danish registries from 1998 to 2018. Median age was 62 years, and 23,308 (7%) were hospitalized with heart failure during follow-up, Dr. Holt said. Of them, 16% claimed at least one NSAID prescription within 2 years and 3% claimed they had at least three prescriptions.

Study follow-up started 120 days after the first-time type 2 diabetes diagnosis and focused on patients who had no previous diagnosis of heart failure or rheumatologic disease. The investigators reported on patients who had one, two, three or four prescriptions for NSAID within a year of starting follow-up.

The study used a case-crossover design, which, the abstract stated, “uses each individual as his or her own control making it suitable to study the effect of short-term exposure on immediate events while mitigating unmeasured confounding.”

Dr. Holt noted that short-term NSAID use was linked to increased risk of heart failure hospitalization (odds ratio, 1.43; 95% confidence interval, 1.27-1.63). The investigators identified even greater risks in three subgroups: age of at least 80 years (OR, 1.78; 95% CI, 1.39-2.28), elevated A1c levels treated with one or less antidiabetic medication (OR 1.68; 95% CI, 1-2.88), and patients without previous NSAID use (OR, 2.71; 95% CI, 1.78-4.23).

In the cohort, celecoxib and naproxen were rarely used (0.4 and 0.9%, respectively), while 3.3% of patients took diclofenac or 12.2% ibuprofen. The latter two NSAIDs had ORs of 1.48 and 1.46, respectively, for hospitalization for new-onset heart failure using 28-day exposure windows (95% CI for both, 1.1­-2 and 1.26-1.69). No increased risk emerged for celecoxib or naproxen.

“High age and A1c levels and being a new user were tied to the strongest associations, along with known use of RASi [renin-angiotensin system inhibitors] and diuretics,” Dr. Holt said. “On the contrary, it seemed safe – from our data – to prescribe short-term NSAIDs for patients below 65 years of age and patients with normal A1c levels.

“Interestingly,” he added, “subclinical structural heart disease among patients with type 2 diabetes could play an important role.”

The findings are noteworthy, Dr. Busui said. “Although there are some limitations with the study design in general when one looks at data extracted from registers, the very large sample size and the fact that the Danish national register captures data in a standardized fashion does make the findings very relevant, especially now that we have confirmed that heart failure is the most prevalent cardiovascular complication in people with diabetes, as we have highlighted in the most recent ADA/ACC consensus on heart failure in diabetes.”

The study received funding from the Danish Heart Foundation and a number of private foundations. Dr. Holt and colleagues have no disclosures. Dr. Busui disclosed relationships with AstraZeneca, Boehringer Ingelheim–Lilly Alliance, Novo Nordisk, Averitas Pharma, Nevro, Regenacy Pharmaceuticals and Roche Diagnostics.

 

People with diabetes who take nonsteroidal anti-inflammatory drugs even on a short-term basis may have about a 50% greater risk of developing heart failure, according to results from a national registry study of more than 330,000 patients to be presented at the annual congress of the European Society of Cardiology.

“According to data from this study, even short-term NSAID use – within 28 days – in patients with type 2 diabetes mellitus are associated with an increased risk of first-time heart failure hospitalization,” lead author Anders Holt, MD, said in an interview.

“Further, it seems that patients above 79 years of age or with elevated hemoglobin A1c levels, along with new users of NSAIDs, are particularly susceptible.” He added that no such association was found in patients below age 65 years with normal A1c levels.

Dr. Holt has a dual appointment as a cardiologist at Copenhagen University and Herlev-Gentofte Hospital in Hellerup, Denmark, and the department of epidemiology and biostatistics at the University of Auckland (New Zealand). Jarl Emmanuel Strange, MD, PhD, a fellow at Copenhagen University, is to present the abstract on Aug. 26.

“This is quite an important observation given that, unfortunately, NSAIDs continue to be prescribed rather easily to people with diabetes and these agents do have risk,” said Rodica Busui, MD, PhD, codirector of the JDRF Center of Excellence at the University of Michigan, Ann Arbor, and president-elect for medicine and science of the American Diabetes Association. Dr. Busui is also lead author of an ADA/American College of Cardiology consensus report on heart failure in diabetes.

The study hypothesized that fluid retention “is a known but underappreciated side effect” of NSAID use and that short-term NSAID use could lead to heart failure in patients with type 2 diabetes, which has been linked to subclinical cardiomyopathy and kidney dysfunction.

“According to this study and particularly the subgroups analyses, it seems that incident heart failure associated with short-term NSAID use could be more than ‘just fluid overload,’ ” Dr. Holt said. “Further investigations into the specific mechanisms causing these associations are warranted.”

The study identified 331,189 patients with type 2 diabetes in nationwide Danish registries from 1998 to 2018. Median age was 62 years, and 23,308 (7%) were hospitalized with heart failure during follow-up, Dr. Holt said. Of them, 16% claimed at least one NSAID prescription within 2 years and 3% claimed they had at least three prescriptions.

Study follow-up started 120 days after the first-time type 2 diabetes diagnosis and focused on patients who had no previous diagnosis of heart failure or rheumatologic disease. The investigators reported on patients who had one, two, three or four prescriptions for NSAID within a year of starting follow-up.

The study used a case-crossover design, which, the abstract stated, “uses each individual as his or her own control making it suitable to study the effect of short-term exposure on immediate events while mitigating unmeasured confounding.”

Dr. Holt noted that short-term NSAID use was linked to increased risk of heart failure hospitalization (odds ratio, 1.43; 95% confidence interval, 1.27-1.63). The investigators identified even greater risks in three subgroups: age of at least 80 years (OR, 1.78; 95% CI, 1.39-2.28), elevated A1c levels treated with one or less antidiabetic medication (OR 1.68; 95% CI, 1-2.88), and patients without previous NSAID use (OR, 2.71; 95% CI, 1.78-4.23).

In the cohort, celecoxib and naproxen were rarely used (0.4 and 0.9%, respectively), while 3.3% of patients took diclofenac or 12.2% ibuprofen. The latter two NSAIDs had ORs of 1.48 and 1.46, respectively, for hospitalization for new-onset heart failure using 28-day exposure windows (95% CI for both, 1.1­-2 and 1.26-1.69). No increased risk emerged for celecoxib or naproxen.

“High age and A1c levels and being a new user were tied to the strongest associations, along with known use of RASi [renin-angiotensin system inhibitors] and diuretics,” Dr. Holt said. “On the contrary, it seemed safe – from our data – to prescribe short-term NSAIDs for patients below 65 years of age and patients with normal A1c levels.

“Interestingly,” he added, “subclinical structural heart disease among patients with type 2 diabetes could play an important role.”

The findings are noteworthy, Dr. Busui said. “Although there are some limitations with the study design in general when one looks at data extracted from registers, the very large sample size and the fact that the Danish national register captures data in a standardized fashion does make the findings very relevant, especially now that we have confirmed that heart failure is the most prevalent cardiovascular complication in people with diabetes, as we have highlighted in the most recent ADA/ACC consensus on heart failure in diabetes.”

The study received funding from the Danish Heart Foundation and a number of private foundations. Dr. Holt and colleagues have no disclosures. Dr. Busui disclosed relationships with AstraZeneca, Boehringer Ingelheim–Lilly Alliance, Novo Nordisk, Averitas Pharma, Nevro, Regenacy Pharmaceuticals and Roche Diagnostics.

 

People with diabetes who take nonsteroidal anti-inflammatory drugs even on a short-term basis may have about a 50% greater risk of developing heart failure, according to results from a national registry study of more than 330,000 patients to be presented at the annual congress of the European Society of Cardiology.

“According to data from this study, even short-term NSAID use – within 28 days – in patients with type 2 diabetes mellitus are associated with an increased risk of first-time heart failure hospitalization,” lead author Anders Holt, MD, said in an interview.

“Further, it seems that patients above 79 years of age or with elevated hemoglobin A1c levels, along with new users of NSAIDs, are particularly susceptible.” He added that no such association was found in patients below age 65 years with normal A1c levels.

Dr. Holt has a dual appointment as a cardiologist at Copenhagen University and Herlev-Gentofte Hospital in Hellerup, Denmark, and the department of epidemiology and biostatistics at the University of Auckland (New Zealand). Jarl Emmanuel Strange, MD, PhD, a fellow at Copenhagen University, is to present the abstract on Aug. 26.

“This is quite an important observation given that, unfortunately, NSAIDs continue to be prescribed rather easily to people with diabetes and these agents do have risk,” said Rodica Busui, MD, PhD, codirector of the JDRF Center of Excellence at the University of Michigan, Ann Arbor, and president-elect for medicine and science of the American Diabetes Association. Dr. Busui is also lead author of an ADA/American College of Cardiology consensus report on heart failure in diabetes.

The study hypothesized that fluid retention “is a known but underappreciated side effect” of NSAID use and that short-term NSAID use could lead to heart failure in patients with type 2 diabetes, which has been linked to subclinical cardiomyopathy and kidney dysfunction.

“According to this study and particularly the subgroups analyses, it seems that incident heart failure associated with short-term NSAID use could be more than ‘just fluid overload,’ ” Dr. Holt said. “Further investigations into the specific mechanisms causing these associations are warranted.”

The study identified 331,189 patients with type 2 diabetes in nationwide Danish registries from 1998 to 2018. Median age was 62 years, and 23,308 (7%) were hospitalized with heart failure during follow-up, Dr. Holt said. Of them, 16% claimed at least one NSAID prescription within 2 years and 3% claimed they had at least three prescriptions.

Study follow-up started 120 days after the first-time type 2 diabetes diagnosis and focused on patients who had no previous diagnosis of heart failure or rheumatologic disease. The investigators reported on patients who had one, two, three or four prescriptions for NSAID within a year of starting follow-up.

The study used a case-crossover design, which, the abstract stated, “uses each individual as his or her own control making it suitable to study the effect of short-term exposure on immediate events while mitigating unmeasured confounding.”

Dr. Holt noted that short-term NSAID use was linked to increased risk of heart failure hospitalization (odds ratio, 1.43; 95% confidence interval, 1.27-1.63). The investigators identified even greater risks in three subgroups: age of at least 80 years (OR, 1.78; 95% CI, 1.39-2.28), elevated A1c levels treated with one or less antidiabetic medication (OR 1.68; 95% CI, 1-2.88), and patients without previous NSAID use (OR, 2.71; 95% CI, 1.78-4.23).

In the cohort, celecoxib and naproxen were rarely used (0.4 and 0.9%, respectively), while 3.3% of patients took diclofenac or 12.2% ibuprofen. The latter two NSAIDs had ORs of 1.48 and 1.46, respectively, for hospitalization for new-onset heart failure using 28-day exposure windows (95% CI for both, 1.1­-2 and 1.26-1.69). No increased risk emerged for celecoxib or naproxen.

“High age and A1c levels and being a new user were tied to the strongest associations, along with known use of RASi [renin-angiotensin system inhibitors] and diuretics,” Dr. Holt said. “On the contrary, it seemed safe – from our data – to prescribe short-term NSAIDs for patients below 65 years of age and patients with normal A1c levels.

“Interestingly,” he added, “subclinical structural heart disease among patients with type 2 diabetes could play an important role.”

The findings are noteworthy, Dr. Busui said. “Although there are some limitations with the study design in general when one looks at data extracted from registers, the very large sample size and the fact that the Danish national register captures data in a standardized fashion does make the findings very relevant, especially now that we have confirmed that heart failure is the most prevalent cardiovascular complication in people with diabetes, as we have highlighted in the most recent ADA/ACC consensus on heart failure in diabetes.”

The study received funding from the Danish Heart Foundation and a number of private foundations. Dr. Holt and colleagues have no disclosures. Dr. Busui disclosed relationships with AstraZeneca, Boehringer Ingelheim–Lilly Alliance, Novo Nordisk, Averitas Pharma, Nevro, Regenacy Pharmaceuticals and Roche Diagnostics.

 

Elderly patients with atrial fibrillation (AF) who are at high risk of bleeding may benefit from a low 15-mg dose of edoxaban, regardless of their frailty status, a subanalysis of the ELDERCARE-AF trial suggests.  

Major bleeding and major or clinically relevant nonmajor bleeding events were both numerically higher in the edoxaban group than placebo, the authors reported, with no heterogeneity by frailty status.

The subanalysis extends findings of the overall study by teasing out stroke, systemic embolism (SSE) and bleeding events across frailty status among Japanese patients aged 80 and older who were ineligible for oral anticoagulants (OACs) at usual doses.

Findings from the original phase 3 ELDERCARE-AF study were previously reported during the virtual European Society of Cardiology Congress 2020 and simultaneously published in The New England Journal of Medicine. The current study was published online in JAMA Network Open.
 

All frailty levels benefited

Shintaro Akashi, MD, PhD, of National Hospital Organization Hamada Medical Center, Shimane, Japan, and colleagues analyzed data from 944 patients randomly assigned to edoxaban 15 mg or placebo for about 3 years. The mean age of participants was 86.6 years and 57% were women. Baseline characteristics, including history of bleeding, were similar between groups.

Patient physical condition was assessed via five parameters: weight loss, grip strength, walking speed, exhaustion, and activity level. This yielded a frailty score, with one point given for each parameter: 0 indicated robust; 1 or 2, prefrail; and 3 or higher, frail. For this analysis, robust (6.5% of patients) and prefrail (51%) were combined and categorized as nonfrail.

In the placebo group, estimated event rates for stroke or SSE were 7.1% per patient-year among frail patients and 6.1% per patient-year among those who were nonfrail.

In the edoxaban group, SSE occurred at an estimated event rate of 2.5% of frail patients and 1.5% of nonfrail patients (adjusted HR, 1.41).

The edoxaban group “consistently had fewer SSE events regardless of frailty status including each frailty assessment parameter, and there was no heterogeneity between the groups,” the authors wrote, with similar trends for the association of edoxaban 15 mg for each frailty assessment parameter.

However, major bleeding and major or clinically relevant nonmajor (CRNM) bleeding events were both higher with edoxaban, regardless of frailty status.

More specifically, in the placebo group, the incidence of major bleeding was 2.3% in the frail group and 1.5% in the nonfrail group (adjusted HR, 1.48) versus 3.7% and 2.9%, respectively, in the edoxaban group (adjusted HR, 1.04).

In addition, exhaustion was related to a significantly increased risk of major or CRNM bleeding in frail versus nonfrail patients (16.3% vs. 8.4%; adjusted HR, 1.97). The incidences were all higher in the edoxaban group, irrespective of frailty status.

Furthermore, although both all-cause death and the net clinical composite outcome of stroke or SSE occurred more frequently in frail than in nonfrail patients, there was no association with frailty status between the edoxaban and placebo groups.

Findings unrelated to edoxaban were also noteworthy. “Surprisingly, grip strength showed an association with adverse events,” the authors wrote. Among those with lower grip strength, “there was nearly a 3-fold increase in risk of SSE and major bleeding and a more than 16-fold significant increase in risk of death. In addition, in those with exhaustion, there was nearly a 2-fold significant increase in major or CRNM bleeding.”

Thus, they suggested, in this patient population, “an objective physical assessment of grip strength or exhaustion in addition to the well-known walking speed may more accurately estimate the risks of clinical outcomes than the overall frailty assessment.”

Head-to-head comparisons needed

Commenting on the findings, Richard Kovach, MD, chair of the interventional cardiology division at Deborah Heart and Lung Center, Browns Mills, N.J., said, “It is interesting that the lower dose of edoxaban still appears to have a statistically significant reduction in the incidence of stroke in this subgroup of extremely frail elderly patients, and it may be useful in this highly selected subset.

“That being said,” he added, “the major complication of oral anticoagulants – major bleeding – appears to be similar to other NOACs prescribed more frequently in the U.S., specifically rivaroxaban and apixaban.”

“Furthermore, in the U.S., frail or complex patients who are not candidates for oral anticoagulant therapy are much more likely to receive a left atrial appendage closure device such as a Watchman or Amulet in order to avoid the risk of bleeding complications completely,” he said. “Procedural success with these devices is extremely high and procedural complications are extremely low. With both devices, the long-term reduction in stroke risk is equivalent to the use of anticoagulant therapy.

“Clearly, more research is needed to compare the outcomes with edoxaban against other NOACs,” Dr. Kovach concluded. “A head-to-head comparison of low-dose edoxaban versus left atrial appendage closure in this high-risk group would also be of great clinical value.”

The study was funded by Daiichi Sankyo. Two coauthors are employees of and five have received fees from the company. Dr. Kovach has reported no relevant financial relationships.

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

Elderly patients with atrial fibrillation (AF) who are at high risk of bleeding may benefit from a low 15-mg dose of edoxaban, regardless of their frailty status, a subanalysis of the ELDERCARE-AF trial suggests.  

Major bleeding and major or clinically relevant nonmajor bleeding events were both numerically higher in the edoxaban group than placebo, the authors reported, with no heterogeneity by frailty status.

The subanalysis extends findings of the overall study by teasing out stroke, systemic embolism (SSE) and bleeding events across frailty status among Japanese patients aged 80 and older who were ineligible for oral anticoagulants (OACs) at usual doses.

Findings from the original phase 3 ELDERCARE-AF study were previously reported during the virtual European Society of Cardiology Congress 2020 and simultaneously published in The New England Journal of Medicine. The current study was published online in JAMA Network Open.
 

All frailty levels benefited

Shintaro Akashi, MD, PhD, of National Hospital Organization Hamada Medical Center, Shimane, Japan, and colleagues analyzed data from 944 patients randomly assigned to edoxaban 15 mg or placebo for about 3 years. The mean age of participants was 86.6 years and 57% were women. Baseline characteristics, including history of bleeding, were similar between groups.

Patient physical condition was assessed via five parameters: weight loss, grip strength, walking speed, exhaustion, and activity level. This yielded a frailty score, with one point given for each parameter: 0 indicated robust; 1 or 2, prefrail; and 3 or higher, frail. For this analysis, robust (6.5% of patients) and prefrail (51%) were combined and categorized as nonfrail.

In the placebo group, estimated event rates for stroke or SSE were 7.1% per patient-year among frail patients and 6.1% per patient-year among those who were nonfrail.

In the edoxaban group, SSE occurred at an estimated event rate of 2.5% of frail patients and 1.5% of nonfrail patients (adjusted HR, 1.41).

The edoxaban group “consistently had fewer SSE events regardless of frailty status including each frailty assessment parameter, and there was no heterogeneity between the groups,” the authors wrote, with similar trends for the association of edoxaban 15 mg for each frailty assessment parameter.

However, major bleeding and major or clinically relevant nonmajor (CRNM) bleeding events were both higher with edoxaban, regardless of frailty status.

More specifically, in the placebo group, the incidence of major bleeding was 2.3% in the frail group and 1.5% in the nonfrail group (adjusted HR, 1.48) versus 3.7% and 2.9%, respectively, in the edoxaban group (adjusted HR, 1.04).

In addition, exhaustion was related to a significantly increased risk of major or CRNM bleeding in frail versus nonfrail patients (16.3% vs. 8.4%; adjusted HR, 1.97). The incidences were all higher in the edoxaban group, irrespective of frailty status.

Furthermore, although both all-cause death and the net clinical composite outcome of stroke or SSE occurred more frequently in frail than in nonfrail patients, there was no association with frailty status between the edoxaban and placebo groups.

Findings unrelated to edoxaban were also noteworthy. “Surprisingly, grip strength showed an association with adverse events,” the authors wrote. Among those with lower grip strength, “there was nearly a 3-fold increase in risk of SSE and major bleeding and a more than 16-fold significant increase in risk of death. In addition, in those with exhaustion, there was nearly a 2-fold significant increase in major or CRNM bleeding.”

Thus, they suggested, in this patient population, “an objective physical assessment of grip strength or exhaustion in addition to the well-known walking speed may more accurately estimate the risks of clinical outcomes than the overall frailty assessment.”

Head-to-head comparisons needed

Commenting on the findings, Richard Kovach, MD, chair of the interventional cardiology division at Deborah Heart and Lung Center, Browns Mills, N.J., said, “It is interesting that the lower dose of edoxaban still appears to have a statistically significant reduction in the incidence of stroke in this subgroup of extremely frail elderly patients, and it may be useful in this highly selected subset.

“That being said,” he added, “the major complication of oral anticoagulants – major bleeding – appears to be similar to other NOACs prescribed more frequently in the U.S., specifically rivaroxaban and apixaban.”

“Furthermore, in the U.S., frail or complex patients who are not candidates for oral anticoagulant therapy are much more likely to receive a left atrial appendage closure device such as a Watchman or Amulet in order to avoid the risk of bleeding complications completely,” he said. “Procedural success with these devices is extremely high and procedural complications are extremely low. With both devices, the long-term reduction in stroke risk is equivalent to the use of anticoagulant therapy.

“Clearly, more research is needed to compare the outcomes with edoxaban against other NOACs,” Dr. Kovach concluded. “A head-to-head comparison of low-dose edoxaban versus left atrial appendage closure in this high-risk group would also be of great clinical value.”

The study was funded by Daiichi Sankyo. Two coauthors are employees of and five have received fees from the company. Dr. Kovach has reported no relevant financial relationships.

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

Elderly patients with atrial fibrillation (AF) who are at high risk of bleeding may benefit from a low 15-mg dose of edoxaban, regardless of their frailty status, a subanalysis of the ELDERCARE-AF trial suggests.  

Major bleeding and major or clinically relevant nonmajor bleeding events were both numerically higher in the edoxaban group than placebo, the authors reported, with no heterogeneity by frailty status.

The subanalysis extends findings of the overall study by teasing out stroke, systemic embolism (SSE) and bleeding events across frailty status among Japanese patients aged 80 and older who were ineligible for oral anticoagulants (OACs) at usual doses.

Findings from the original phase 3 ELDERCARE-AF study were previously reported during the virtual European Society of Cardiology Congress 2020 and simultaneously published in The New England Journal of Medicine. The current study was published online in JAMA Network Open.
 

All frailty levels benefited

Shintaro Akashi, MD, PhD, of National Hospital Organization Hamada Medical Center, Shimane, Japan, and colleagues analyzed data from 944 patients randomly assigned to edoxaban 15 mg or placebo for about 3 years. The mean age of participants was 86.6 years and 57% were women. Baseline characteristics, including history of bleeding, were similar between groups.

Patient physical condition was assessed via five parameters: weight loss, grip strength, walking speed, exhaustion, and activity level. This yielded a frailty score, with one point given for each parameter: 0 indicated robust; 1 or 2, prefrail; and 3 or higher, frail. For this analysis, robust (6.5% of patients) and prefrail (51%) were combined and categorized as nonfrail.

In the placebo group, estimated event rates for stroke or SSE were 7.1% per patient-year among frail patients and 6.1% per patient-year among those who were nonfrail.

In the edoxaban group, SSE occurred at an estimated event rate of 2.5% of frail patients and 1.5% of nonfrail patients (adjusted HR, 1.41).

The edoxaban group “consistently had fewer SSE events regardless of frailty status including each frailty assessment parameter, and there was no heterogeneity between the groups,” the authors wrote, with similar trends for the association of edoxaban 15 mg for each frailty assessment parameter.

However, major bleeding and major or clinically relevant nonmajor (CRNM) bleeding events were both higher with edoxaban, regardless of frailty status.

More specifically, in the placebo group, the incidence of major bleeding was 2.3% in the frail group and 1.5% in the nonfrail group (adjusted HR, 1.48) versus 3.7% and 2.9%, respectively, in the edoxaban group (adjusted HR, 1.04).

In addition, exhaustion was related to a significantly increased risk of major or CRNM bleeding in frail versus nonfrail patients (16.3% vs. 8.4%; adjusted HR, 1.97). The incidences were all higher in the edoxaban group, irrespective of frailty status.

Furthermore, although both all-cause death and the net clinical composite outcome of stroke or SSE occurred more frequently in frail than in nonfrail patients, there was no association with frailty status between the edoxaban and placebo groups.

Findings unrelated to edoxaban were also noteworthy. “Surprisingly, grip strength showed an association with adverse events,” the authors wrote. Among those with lower grip strength, “there was nearly a 3-fold increase in risk of SSE and major bleeding and a more than 16-fold significant increase in risk of death. In addition, in those with exhaustion, there was nearly a 2-fold significant increase in major or CRNM bleeding.”

Thus, they suggested, in this patient population, “an objective physical assessment of grip strength or exhaustion in addition to the well-known walking speed may more accurately estimate the risks of clinical outcomes than the overall frailty assessment.”

Head-to-head comparisons needed

Commenting on the findings, Richard Kovach, MD, chair of the interventional cardiology division at Deborah Heart and Lung Center, Browns Mills, N.J., said, “It is interesting that the lower dose of edoxaban still appears to have a statistically significant reduction in the incidence of stroke in this subgroup of extremely frail elderly patients, and it may be useful in this highly selected subset.

“That being said,” he added, “the major complication of oral anticoagulants – major bleeding – appears to be similar to other NOACs prescribed more frequently in the U.S., specifically rivaroxaban and apixaban.”

“Furthermore, in the U.S., frail or complex patients who are not candidates for oral anticoagulant therapy are much more likely to receive a left atrial appendage closure device such as a Watchman or Amulet in order to avoid the risk of bleeding complications completely,” he said. “Procedural success with these devices is extremely high and procedural complications are extremely low. With both devices, the long-term reduction in stroke risk is equivalent to the use of anticoagulant therapy.

“Clearly, more research is needed to compare the outcomes with edoxaban against other NOACs,” Dr. Kovach concluded. “A head-to-head comparison of low-dose edoxaban versus left atrial appendage closure in this high-risk group would also be of great clinical value.”

The study was funded by Daiichi Sankyo. Two coauthors are employees of and five have received fees from the company. Dr. Kovach has reported no relevant financial relationships.

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

Questions about how to prescribe statins for primary prevention abound more than 3 decades after the drugs swept into clinical practice to become a first-line medical approach to cutting cardiovascular (CV) risk. Statin usage recommendations from different bodies can vary in ways both limited and fundamental, spurring the kind of debate that accompanies such a document newly issued by the United States Preventive Services Task Force.

The document, little changed from the draft guidance released for public comment in February, was published online Aug. 23 in JAMA and the USPSTF website. It replaces a similar document issued by the task force in 2016.

The guidance has much in common with, but also sharp differences from, the influential 2018 guidelines on blood cholesterol management developed by the American College of Cardiology, American Heart Association, and 10 other medical societies.

And it is provocative enough to elicit at least four editorials issued the same day across the JAMA family of journals. They highlight key differences between the two documents, among them the USPSTF guidance’s consistent, narrow reliance on 7.5% and 10% cut points for 10-year risk levels as estimated from the ACC/AHA pooled cohort equations (PCE).  

The guidance pairs the 10-year risk metric with at least one of only four prescribed CV risk factors to arrive at a limited choice of statin therapy recommendations. But its decision process isn’t bolstered by coronary artery calcium (CAC) scores or the prespecified “risk enhancers” that allowed the ACC/AHA-multisociety guidelines to be applied broadly and still be closely personalized. Those guidelines provide more PCE-based risk tiers for greater discrimination of risk and allow statins to be considered across a broader age group.

The USPSTF guidance’s evidence base consists of 23 clinical trials and three observational studies that directly compared a statin to either placebo or no statin, task force member John B. Wong, MD, Tufts University School of Medicine, Boston, told this news organization.

“In either kind of study, we found that the vast majority of patients had one or more of four risk factors – dyslipidemia, hypertension, diabetes, or smoking. So, when we categorized high risk or increased risk, we included the presence of one or more of those risk factors,” said Dr. Wong, who is director of comparative effectiveness research at Tufts Clinical Translational Science Institute.
 

‘Sensible and practical’

The USPSTF guidance applies only to adults aged 40-75 without CV signs or symptoms and recommends a statin prescription for persons at “high risk,” that is with an estimated 10-year PCE-based risk for death or CV events of 10% or higher plus at least one of the four risk factors, a level B recommendation.

It recommends that “clinicians selectively offer a statin” to such persons at “increased risk,” who have at least one of the risk factors and an estimated 10-year risk for death or CV events of 7.5% to less than 10%, a level C recommendation. “The likelihood of benefit is smaller in this group” than in persons at high risk, the document states.

“These recommendations from the USPSTF are sensible and practical,” states Salim S. Virani, MD, PhD, DeBakey Veterans Affairs Medical Center, Houston, in a related editorial published the same day in JAMA Network Open. He calls the former B-level recommendation “a conservative approach” and the latter C-level recommendation a “nuanced approach.”

Both are “understandable” given that some studies suggest that the PCE may overestimate the CV risk, Dr. Virani observes. “On the other hand, statin therapy has been shown to be efficacious” at 10-year CV-risk levels down to about 5%.

The USPSTF document “I think is going to perpetuate a problem that we have in this country, which is vast undertreatment of lipids,” Eric D. Peterson, MD, MPH, University of Texas Southwestern Medical Center, Dallas, said in an interview.

“We have a ton of good drugs that can lower cholesterol like crazy. If you lower cholesterol a lot, you improve outcomes,” he said. Dyslipidemia needs to be more widely and consistently treated, but “right now we have a pool of people in primary prevention who undertreat lipids and wait until disease happens – and then cardiologists get engaged. That’s an avoidable miss,” Dr. Peterson adds. He and JAMA Cardiology associate editor Ann Marie Navar, MD, PhD, provided JAMA with an editorial that accompanies the USPSTF guidance.

“My own personal bias would be that the [ACC/AHA-multisociety guidelines] are closer to being right,” Dr. Peterson said. They – unlike the USPSTF guidance – cover people with risk levels below 7.5%, down to at least 5%. They allow risk enhancers like metabolic syndrome, inflammatory diseases, or family history into the decision process. “And they’re more aggressive in diabetes and more aggressive in older people,” he said.
 

Higher threshold for therapy

The USPSTF guidance also explicitly omits some high-risk groups and makes little accommodation for others who might especially benefit from statins, several of the editorials contend. For example, states a related JAMA Cardiology editorial published the same day, “The USPSTF does not comment on familial hypercholesterolemia or an LDL-C level of 190 mg/dL or higher,” yet they are covered by the ACC/AHA-multispecialty guidelines.

In addition, write the editorialists, led by Neil J. Stone, MD, Northwestern University, Chicago, “the USPSTF uses a slightly higher threshold for initiation of statin therapy” than was used in the ACC/AHA-multisociety guidelines. USPSTF, for example, calls for 10-year risk to reach 10% before recommending a statin prescription.

“One concern about the USPSTF setting the bar higher for statin initiation is that it reduces the number of young patients (age 40-50 years) at risk for premature myocardial infarction considered for treatment,” write Dr. Stone and colleagues.

That may be related to a weakness of the PCE-based decision process. “Because the PCE estimates of 10-year CV disease risk rely so heavily on age, sex, and race, use of these estimates to identify candidates for statins results in significant skewing of the population recommended for statins,” write Dr. Navar and Dr. Peterson in their JAMA editorial.

The risk enhancers in the ACC/AHA-multispecialty guidelines, about a dozen of them, compensate for that limitation to some extent. But the PCE-dominated USPSTF risk estimates will likely miss some groups that could potentially benefit from statin therapy, Dr. Peterson agreed in an interview.  

For example, younger adults facing years of high LDL-cholesterol levels could easily have PCE-based 10-year risk below 10%. “Having a high LDL over a lifetime puts you at really high risk,” he said. “Young people are missed even though their longitudinal risk is high.” So, by waiting for the lofty 10% level of risk over 10 years, “we limit the use of medicine that’s pretty cheap and highly effective.”

Dose intensity, adverse events

Also at variance from the ACC/AHA-multispecialty guidelines, the USPSTF states that, “Based on available evidence, use of moderate-intensity statin therapy seems reasonable for the primary prevention of CV disease in most persons.”  

The task force specifically explored whether evidence supports some use of high-intensity vs. moderate-intensity statins, Tufts University’s Dr. Wong said. “We found only one study that looked at that particular question, and it didn’t give us a strong answer.” An elevated rosuvastatin-related diabetes risk was apparent in the JUPITER trial, “but for the other studies, we did not find that association.”  

Most of the studies that explored statins for reducing risk for a first stroke or myocardial infarction used a moderate-dose statin, Dr. Wong said. “So that’s what we would usually recommend.”

But, Dr. Virani writes, consistent with the ACC/AHA-multispecialty guidelines, “clinicians should consider titrating the intensity of therapy to the risk of the individual.” Persons in certain high-risk primary prevention groups, such as those with end-organ injury from diabetes or LDL cholesterol at least 190 mg/dL, “may derive further benefit from the use of high-intensity statin therapy.”

Low-intensity statins are another potential option, but “in contrast with its 2016 recommendations, the USPSTF no longer recommends use of low-intensity statins in certain situations,” observes a fourth editorial published the same day in JAMA Internal Medicine, with lead author Anand R. Habib, MD, MPhil, and senior author Rita F. Redberg, MD, MSc, both of the University of California, San Francisco. Dr. Redberg is the journal’s editor and has long expressed cautions about statin safety.

“While it is understandable that the Task Force was limited by lack of data on dosing, this change is unfortunate for patients because the frequency of adverse effects increases as the statin dose increases,” the editorial states. Although USPSTF did not find statistically significant harm from the drugs, “in clinical practice, adverse events are commonly reported with use of statins.”

It continues: “At present, there are further reasons to curb our enthusiasm about the use of statins for primary prevention of CV disease.” To illustrate, the editorial questioned primary-prevention statins’ balance of risk vs. clinically meaningful benefit, not benefit that is merely statistically significant.

“The purported benefits of statins in terms of relative risk reduction are fairly constant across baseline lipid levels and cardiovascular risk score categories for primary prevention,” the editorial states.

“Therefore, the absolute benefit for those in lower-risk categories is likely small given that their baseline absolute risk is low, while the chance of adverse effects is constant across risk categories.”

However, USPSTF states, “In pooled analyses of trial data, statin therapy was not associated with increased risk of study withdrawal due to adverse events or serious adverse events.” Nor did it find significant associations with cancers, liver enzyme abnormalities, or diabetes, including new-onset diabetes.

And, the USPSTF adds, “Evidence on the association between statins and renal or cognitive harms is very limited but does not indicate increased risk.”

USPSTF is supported by the U.S. Agency for Healthcare Research and Quality. Dr. Virani discloses receiving grants from the Department of Veterans Affairs, National Institutes of Health, and the World Heart Federation; and personal fees from the American College of Cardiology. Dr. Peterson discloses serving on the JAMA editorial board and receiving research support to his institution from Amgen, Bristol-Myers Squibb, Esperion, and Janssen; and consulting fees from Novo Nordisk, Bayer, and Novartis. Dr. Navar discloses receiving research support to her institution from Amgen, Bristol-Myers Squibb, Esperion, and Janssen; and receiving honoraria and consulting fees from AstraZeneca, Boehringer Ingelheim, Bayer, Janssen, Lilly, Novo Nordisk, Novartis, New Amsterdam, and Pfizer. Dr. Stone discloses receiving an honorarium from Knowledge to Practice, an educational company not associated with the pharmaceutical industry; disclosures for the other authors are in the report. Dr. Redberg discloses receiving research funding from the Arnold Ventures Foundation and the Greenwall Foundation.

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

Questions about how to prescribe statins for primary prevention abound more than 3 decades after the drugs swept into clinical practice to become a first-line medical approach to cutting cardiovascular (CV) risk. Statin usage recommendations from different bodies can vary in ways both limited and fundamental, spurring the kind of debate that accompanies such a document newly issued by the United States Preventive Services Task Force.

The document, little changed from the draft guidance released for public comment in February, was published online Aug. 23 in JAMA and the USPSTF website. It replaces a similar document issued by the task force in 2016.

The guidance has much in common with, but also sharp differences from, the influential 2018 guidelines on blood cholesterol management developed by the American College of Cardiology, American Heart Association, and 10 other medical societies.

And it is provocative enough to elicit at least four editorials issued the same day across the JAMA family of journals. They highlight key differences between the two documents, among them the USPSTF guidance’s consistent, narrow reliance on 7.5% and 10% cut points for 10-year risk levels as estimated from the ACC/AHA pooled cohort equations (PCE).  

The guidance pairs the 10-year risk metric with at least one of only four prescribed CV risk factors to arrive at a limited choice of statin therapy recommendations. But its decision process isn’t bolstered by coronary artery calcium (CAC) scores or the prespecified “risk enhancers” that allowed the ACC/AHA-multisociety guidelines to be applied broadly and still be closely personalized. Those guidelines provide more PCE-based risk tiers for greater discrimination of risk and allow statins to be considered across a broader age group.

The USPSTF guidance’s evidence base consists of 23 clinical trials and three observational studies that directly compared a statin to either placebo or no statin, task force member John B. Wong, MD, Tufts University School of Medicine, Boston, told this news organization.

“In either kind of study, we found that the vast majority of patients had one or more of four risk factors – dyslipidemia, hypertension, diabetes, or smoking. So, when we categorized high risk or increased risk, we included the presence of one or more of those risk factors,” said Dr. Wong, who is director of comparative effectiveness research at Tufts Clinical Translational Science Institute.
 

‘Sensible and practical’

The USPSTF guidance applies only to adults aged 40-75 without CV signs or symptoms and recommends a statin prescription for persons at “high risk,” that is with an estimated 10-year PCE-based risk for death or CV events of 10% or higher plus at least one of the four risk factors, a level B recommendation.

It recommends that “clinicians selectively offer a statin” to such persons at “increased risk,” who have at least one of the risk factors and an estimated 10-year risk for death or CV events of 7.5% to less than 10%, a level C recommendation. “The likelihood of benefit is smaller in this group” than in persons at high risk, the document states.

“These recommendations from the USPSTF are sensible and practical,” states Salim S. Virani, MD, PhD, DeBakey Veterans Affairs Medical Center, Houston, in a related editorial published the same day in JAMA Network Open. He calls the former B-level recommendation “a conservative approach” and the latter C-level recommendation a “nuanced approach.”

Both are “understandable” given that some studies suggest that the PCE may overestimate the CV risk, Dr. Virani observes. “On the other hand, statin therapy has been shown to be efficacious” at 10-year CV-risk levels down to about 5%.

The USPSTF document “I think is going to perpetuate a problem that we have in this country, which is vast undertreatment of lipids,” Eric D. Peterson, MD, MPH, University of Texas Southwestern Medical Center, Dallas, said in an interview.

“We have a ton of good drugs that can lower cholesterol like crazy. If you lower cholesterol a lot, you improve outcomes,” he said. Dyslipidemia needs to be more widely and consistently treated, but “right now we have a pool of people in primary prevention who undertreat lipids and wait until disease happens – and then cardiologists get engaged. That’s an avoidable miss,” Dr. Peterson adds. He and JAMA Cardiology associate editor Ann Marie Navar, MD, PhD, provided JAMA with an editorial that accompanies the USPSTF guidance.

“My own personal bias would be that the [ACC/AHA-multisociety guidelines] are closer to being right,” Dr. Peterson said. They – unlike the USPSTF guidance – cover people with risk levels below 7.5%, down to at least 5%. They allow risk enhancers like metabolic syndrome, inflammatory diseases, or family history into the decision process. “And they’re more aggressive in diabetes and more aggressive in older people,” he said.
 

Higher threshold for therapy

The USPSTF guidance also explicitly omits some high-risk groups and makes little accommodation for others who might especially benefit from statins, several of the editorials contend. For example, states a related JAMA Cardiology editorial published the same day, “The USPSTF does not comment on familial hypercholesterolemia or an LDL-C level of 190 mg/dL or higher,” yet they are covered by the ACC/AHA-multispecialty guidelines.

In addition, write the editorialists, led by Neil J. Stone, MD, Northwestern University, Chicago, “the USPSTF uses a slightly higher threshold for initiation of statin therapy” than was used in the ACC/AHA-multisociety guidelines. USPSTF, for example, calls for 10-year risk to reach 10% before recommending a statin prescription.

“One concern about the USPSTF setting the bar higher for statin initiation is that it reduces the number of young patients (age 40-50 years) at risk for premature myocardial infarction considered for treatment,” write Dr. Stone and colleagues.

That may be related to a weakness of the PCE-based decision process. “Because the PCE estimates of 10-year CV disease risk rely so heavily on age, sex, and race, use of these estimates to identify candidates for statins results in significant skewing of the population recommended for statins,” write Dr. Navar and Dr. Peterson in their JAMA editorial.

The risk enhancers in the ACC/AHA-multispecialty guidelines, about a dozen of them, compensate for that limitation to some extent. But the PCE-dominated USPSTF risk estimates will likely miss some groups that could potentially benefit from statin therapy, Dr. Peterson agreed in an interview.  

For example, younger adults facing years of high LDL-cholesterol levels could easily have PCE-based 10-year risk below 10%. “Having a high LDL over a lifetime puts you at really high risk,” he said. “Young people are missed even though their longitudinal risk is high.” So, by waiting for the lofty 10% level of risk over 10 years, “we limit the use of medicine that’s pretty cheap and highly effective.”

Dose intensity, adverse events

Also at variance from the ACC/AHA-multispecialty guidelines, the USPSTF states that, “Based on available evidence, use of moderate-intensity statin therapy seems reasonable for the primary prevention of CV disease in most persons.”  

The task force specifically explored whether evidence supports some use of high-intensity vs. moderate-intensity statins, Tufts University’s Dr. Wong said. “We found only one study that looked at that particular question, and it didn’t give us a strong answer.” An elevated rosuvastatin-related diabetes risk was apparent in the JUPITER trial, “but for the other studies, we did not find that association.”  

Most of the studies that explored statins for reducing risk for a first stroke or myocardial infarction used a moderate-dose statin, Dr. Wong said. “So that’s what we would usually recommend.”

But, Dr. Virani writes, consistent with the ACC/AHA-multispecialty guidelines, “clinicians should consider titrating the intensity of therapy to the risk of the individual.” Persons in certain high-risk primary prevention groups, such as those with end-organ injury from diabetes or LDL cholesterol at least 190 mg/dL, “may derive further benefit from the use of high-intensity statin therapy.”

Low-intensity statins are another potential option, but “in contrast with its 2016 recommendations, the USPSTF no longer recommends use of low-intensity statins in certain situations,” observes a fourth editorial published the same day in JAMA Internal Medicine, with lead author Anand R. Habib, MD, MPhil, and senior author Rita F. Redberg, MD, MSc, both of the University of California, San Francisco. Dr. Redberg is the journal’s editor and has long expressed cautions about statin safety.

“While it is understandable that the Task Force was limited by lack of data on dosing, this change is unfortunate for patients because the frequency of adverse effects increases as the statin dose increases,” the editorial states. Although USPSTF did not find statistically significant harm from the drugs, “in clinical practice, adverse events are commonly reported with use of statins.”

It continues: “At present, there are further reasons to curb our enthusiasm about the use of statins for primary prevention of CV disease.” To illustrate, the editorial questioned primary-prevention statins’ balance of risk vs. clinically meaningful benefit, not benefit that is merely statistically significant.

“The purported benefits of statins in terms of relative risk reduction are fairly constant across baseline lipid levels and cardiovascular risk score categories for primary prevention,” the editorial states.

“Therefore, the absolute benefit for those in lower-risk categories is likely small given that their baseline absolute risk is low, while the chance of adverse effects is constant across risk categories.”

However, USPSTF states, “In pooled analyses of trial data, statin therapy was not associated with increased risk of study withdrawal due to adverse events or serious adverse events.” Nor did it find significant associations with cancers, liver enzyme abnormalities, or diabetes, including new-onset diabetes.

And, the USPSTF adds, “Evidence on the association between statins and renal or cognitive harms is very limited but does not indicate increased risk.”

USPSTF is supported by the U.S. Agency for Healthcare Research and Quality. Dr. Virani discloses receiving grants from the Department of Veterans Affairs, National Institutes of Health, and the World Heart Federation; and personal fees from the American College of Cardiology. Dr. Peterson discloses serving on the JAMA editorial board and receiving research support to his institution from Amgen, Bristol-Myers Squibb, Esperion, and Janssen; and consulting fees from Novo Nordisk, Bayer, and Novartis. Dr. Navar discloses receiving research support to her institution from Amgen, Bristol-Myers Squibb, Esperion, and Janssen; and receiving honoraria and consulting fees from AstraZeneca, Boehringer Ingelheim, Bayer, Janssen, Lilly, Novo Nordisk, Novartis, New Amsterdam, and Pfizer. Dr. Stone discloses receiving an honorarium from Knowledge to Practice, an educational company not associated with the pharmaceutical industry; disclosures for the other authors are in the report. Dr. Redberg discloses receiving research funding from the Arnold Ventures Foundation and the Greenwall Foundation.

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

Questions about how to prescribe statins for primary prevention abound more than 3 decades after the drugs swept into clinical practice to become a first-line medical approach to cutting cardiovascular (CV) risk. Statin usage recommendations from different bodies can vary in ways both limited and fundamental, spurring the kind of debate that accompanies such a document newly issued by the United States Preventive Services Task Force.

The document, little changed from the draft guidance released for public comment in February, was published online Aug. 23 in JAMA and the USPSTF website. It replaces a similar document issued by the task force in 2016.

The guidance has much in common with, but also sharp differences from, the influential 2018 guidelines on blood cholesterol management developed by the American College of Cardiology, American Heart Association, and 10 other medical societies.

And it is provocative enough to elicit at least four editorials issued the same day across the JAMA family of journals. They highlight key differences between the two documents, among them the USPSTF guidance’s consistent, narrow reliance on 7.5% and 10% cut points for 10-year risk levels as estimated from the ACC/AHA pooled cohort equations (PCE).  

The guidance pairs the 10-year risk metric with at least one of only four prescribed CV risk factors to arrive at a limited choice of statin therapy recommendations. But its decision process isn’t bolstered by coronary artery calcium (CAC) scores or the prespecified “risk enhancers” that allowed the ACC/AHA-multisociety guidelines to be applied broadly and still be closely personalized. Those guidelines provide more PCE-based risk tiers for greater discrimination of risk and allow statins to be considered across a broader age group.

The USPSTF guidance’s evidence base consists of 23 clinical trials and three observational studies that directly compared a statin to either placebo or no statin, task force member John B. Wong, MD, Tufts University School of Medicine, Boston, told this news organization.

“In either kind of study, we found that the vast majority of patients had one or more of four risk factors – dyslipidemia, hypertension, diabetes, or smoking. So, when we categorized high risk or increased risk, we included the presence of one or more of those risk factors,” said Dr. Wong, who is director of comparative effectiveness research at Tufts Clinical Translational Science Institute.
 

‘Sensible and practical’

The USPSTF guidance applies only to adults aged 40-75 without CV signs or symptoms and recommends a statin prescription for persons at “high risk,” that is with an estimated 10-year PCE-based risk for death or CV events of 10% or higher plus at least one of the four risk factors, a level B recommendation.

It recommends that “clinicians selectively offer a statin” to such persons at “increased risk,” who have at least one of the risk factors and an estimated 10-year risk for death or CV events of 7.5% to less than 10%, a level C recommendation. “The likelihood of benefit is smaller in this group” than in persons at high risk, the document states.

“These recommendations from the USPSTF are sensible and practical,” states Salim S. Virani, MD, PhD, DeBakey Veterans Affairs Medical Center, Houston, in a related editorial published the same day in JAMA Network Open. He calls the former B-level recommendation “a conservative approach” and the latter C-level recommendation a “nuanced approach.”

Both are “understandable” given that some studies suggest that the PCE may overestimate the CV risk, Dr. Virani observes. “On the other hand, statin therapy has been shown to be efficacious” at 10-year CV-risk levels down to about 5%.

The USPSTF document “I think is going to perpetuate a problem that we have in this country, which is vast undertreatment of lipids,” Eric D. Peterson, MD, MPH, University of Texas Southwestern Medical Center, Dallas, said in an interview.

“We have a ton of good drugs that can lower cholesterol like crazy. If you lower cholesterol a lot, you improve outcomes,” he said. Dyslipidemia needs to be more widely and consistently treated, but “right now we have a pool of people in primary prevention who undertreat lipids and wait until disease happens – and then cardiologists get engaged. That’s an avoidable miss,” Dr. Peterson adds. He and JAMA Cardiology associate editor Ann Marie Navar, MD, PhD, provided JAMA with an editorial that accompanies the USPSTF guidance.

“My own personal bias would be that the [ACC/AHA-multisociety guidelines] are closer to being right,” Dr. Peterson said. They – unlike the USPSTF guidance – cover people with risk levels below 7.5%, down to at least 5%. They allow risk enhancers like metabolic syndrome, inflammatory diseases, or family history into the decision process. “And they’re more aggressive in diabetes and more aggressive in older people,” he said.
 

Higher threshold for therapy

The USPSTF guidance also explicitly omits some high-risk groups and makes little accommodation for others who might especially benefit from statins, several of the editorials contend. For example, states a related JAMA Cardiology editorial published the same day, “The USPSTF does not comment on familial hypercholesterolemia or an LDL-C level of 190 mg/dL or higher,” yet they are covered by the ACC/AHA-multispecialty guidelines.

In addition, write the editorialists, led by Neil J. Stone, MD, Northwestern University, Chicago, “the USPSTF uses a slightly higher threshold for initiation of statin therapy” than was used in the ACC/AHA-multisociety guidelines. USPSTF, for example, calls for 10-year risk to reach 10% before recommending a statin prescription.

“One concern about the USPSTF setting the bar higher for statin initiation is that it reduces the number of young patients (age 40-50 years) at risk for premature myocardial infarction considered for treatment,” write Dr. Stone and colleagues.

That may be related to a weakness of the PCE-based decision process. “Because the PCE estimates of 10-year CV disease risk rely so heavily on age, sex, and race, use of these estimates to identify candidates for statins results in significant skewing of the population recommended for statins,” write Dr. Navar and Dr. Peterson in their JAMA editorial.

The risk enhancers in the ACC/AHA-multispecialty guidelines, about a dozen of them, compensate for that limitation to some extent. But the PCE-dominated USPSTF risk estimates will likely miss some groups that could potentially benefit from statin therapy, Dr. Peterson agreed in an interview.  

For example, younger adults facing years of high LDL-cholesterol levels could easily have PCE-based 10-year risk below 10%. “Having a high LDL over a lifetime puts you at really high risk,” he said. “Young people are missed even though their longitudinal risk is high.” So, by waiting for the lofty 10% level of risk over 10 years, “we limit the use of medicine that’s pretty cheap and highly effective.”

Dose intensity, adverse events

Also at variance from the ACC/AHA-multispecialty guidelines, the USPSTF states that, “Based on available evidence, use of moderate-intensity statin therapy seems reasonable for the primary prevention of CV disease in most persons.”  

The task force specifically explored whether evidence supports some use of high-intensity vs. moderate-intensity statins, Tufts University’s Dr. Wong said. “We found only one study that looked at that particular question, and it didn’t give us a strong answer.” An elevated rosuvastatin-related diabetes risk was apparent in the JUPITER trial, “but for the other studies, we did not find that association.”  

Most of the studies that explored statins for reducing risk for a first stroke or myocardial infarction used a moderate-dose statin, Dr. Wong said. “So that’s what we would usually recommend.”

But, Dr. Virani writes, consistent with the ACC/AHA-multispecialty guidelines, “clinicians should consider titrating the intensity of therapy to the risk of the individual.” Persons in certain high-risk primary prevention groups, such as those with end-organ injury from diabetes or LDL cholesterol at least 190 mg/dL, “may derive further benefit from the use of high-intensity statin therapy.”

Low-intensity statins are another potential option, but “in contrast with its 2016 recommendations, the USPSTF no longer recommends use of low-intensity statins in certain situations,” observes a fourth editorial published the same day in JAMA Internal Medicine, with lead author Anand R. Habib, MD, MPhil, and senior author Rita F. Redberg, MD, MSc, both of the University of California, San Francisco. Dr. Redberg is the journal’s editor and has long expressed cautions about statin safety.

“While it is understandable that the Task Force was limited by lack of data on dosing, this change is unfortunate for patients because the frequency of adverse effects increases as the statin dose increases,” the editorial states. Although USPSTF did not find statistically significant harm from the drugs, “in clinical practice, adverse events are commonly reported with use of statins.”

It continues: “At present, there are further reasons to curb our enthusiasm about the use of statins for primary prevention of CV disease.” To illustrate, the editorial questioned primary-prevention statins’ balance of risk vs. clinically meaningful benefit, not benefit that is merely statistically significant.

“The purported benefits of statins in terms of relative risk reduction are fairly constant across baseline lipid levels and cardiovascular risk score categories for primary prevention,” the editorial states.

“Therefore, the absolute benefit for those in lower-risk categories is likely small given that their baseline absolute risk is low, while the chance of adverse effects is constant across risk categories.”

However, USPSTF states, “In pooled analyses of trial data, statin therapy was not associated with increased risk of study withdrawal due to adverse events or serious adverse events.” Nor did it find significant associations with cancers, liver enzyme abnormalities, or diabetes, including new-onset diabetes.

And, the USPSTF adds, “Evidence on the association between statins and renal or cognitive harms is very limited but does not indicate increased risk.”

USPSTF is supported by the U.S. Agency for Healthcare Research and Quality. Dr. Virani discloses receiving grants from the Department of Veterans Affairs, National Institutes of Health, and the World Heart Federation; and personal fees from the American College of Cardiology. Dr. Peterson discloses serving on the JAMA editorial board and receiving research support to his institution from Amgen, Bristol-Myers Squibb, Esperion, and Janssen; and consulting fees from Novo Nordisk, Bayer, and Novartis. Dr. Navar discloses receiving research support to her institution from Amgen, Bristol-Myers Squibb, Esperion, and Janssen; and receiving honoraria and consulting fees from AstraZeneca, Boehringer Ingelheim, Bayer, Janssen, Lilly, Novo Nordisk, Novartis, New Amsterdam, and Pfizer. Dr. Stone discloses receiving an honorarium from Knowledge to Practice, an educational company not associated with the pharmaceutical industry; disclosures for the other authors are in the report. Dr. Redberg discloses receiving research funding from the Arnold Ventures Foundation and the Greenwall Foundation.

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

After 2 years of virtual gatherings, the annual European Society of Cardiology Congress 2022 is back and celebrating its 70th birthday live in the raucously beautiful city of Barcelona.

Much of the upcoming event, scheduled for Aug. 26 to 29, however, will also be broadcast online, and the full program will be available on-demand after the meeting.

The hybrid format is intentional, leveraging the social interaction that only live meetings can provide and the global reach of online access, Program Committee Chair Stephan Windecker, MD, Bern University Hospital, Switzerland, told this news organization.

“It enables a lot of people who, for some reason, cannot travel to still connect, and it also provides what we’ve done in the past, but I think in a more natural way of doing it,” he said. “You can connect later on again, read, digest, look at sessions that you may have missed, and that’s a nice experience to take advantage of.”

Thus far, early registrations are favoring the sunny climes, with about 14,000 onsite and 4,200 online attendees.

This year’s spotlight theme is cardiac imaging, with programming throughout the Congress devoted to its role in diagnosis, treatment, follow-up, and, increasingly, guidance of interventions.

“Particularly as it relates to the transcatheter heart valves, it’s really a new discipline, and I think you can’t overemphasize that enough, because the interventional result directly depends on the quality of imaging,” Dr. Windecker said. “This will certainly logarithmically increase during the next few years.”

The always highly anticipated Hot Line sessions mushroomed this year to 10, featuring 36 studies, up from just 4 sessions and 20 studies last year.

“Especially during the COVID pandemic, many investigators and trialists experienced difficulties in recruitment, difficulties in terms of also personnel shortages, and so on. So really, we feel very privileged at the large number of submissions,” he said. “I think there are really very interesting ones, which we tried to spread throughout the 4 days.”
 

Hot Line sessions 1-5

Among the studies Dr. Windecker highlighted is TIME, which kicks off Hot Line 1 on Friday, Aug. 26, and aimed to establish whether antihypertensive medications taken at night are truly more cardioprotective than those taken in the morning.

The topic has been hotly debated, with proponents pointing to a near halving of mortality and cardiovascular events with bedtime dosing in the Hygia Chronotherapy trial. Skeptics question the validity and conduct of the trial, however, prompting an investigation by the European Heart Journal, which found no evidence of misconduct but has many looking for more definitive data.

Also in this session is SECURE, pitting a cardiovascular polypill that contains aspirin, ramipril, and atorvastatin against usual care in secondary prevention, and PERSPECTIVE, comparing the effects of sacubitril/valsartan with valsartan on cognitive function in patients with chronic heart failure and preserved ejection fraction (HFpEF).

Hot Line 2, the first of three Hot Lines taking place on Saturday, Aug. 27, features the Danish cardiovascular screening trial DANCAVAS, the phase 4 ADVOR trial of acetazolamide (Diamox) in acute decompensated heart failure (HF), and the DANFLU-1 trial of high- versus standard-dose influenza vaccine in the elderly.

Also on tap is the BOX trial, comparing two blood pressure and two oxygenation targets in comatose out-of-hospital cardiac arrest patients.

“It addresses an understudied patient population, and the second element is that sometimes things you do out of ordinary application – so, the application of oxygen – may have beneficial but also adverse impact,” Dr. Windecker said. “So, to study this in a randomized clinical trial is really important.”

Additionally, he highlighted REVIVED, which will be presented in Hot Line 3 and is the first trial to examine percutaneous coronary intervention (PCI) with optimal medical therapy (OMT) versus OMT alone in the setting of severe ischemic cardiomyopathy.

“We have data from the STICH trial, where surgical revascularization was investigated in ischemic cardiomyopathy, but the open question is: What about PCI as revascularization?” Dr. Windecker said. “The other reason it’s interesting is that we have these evidence-based drugs that have dramatically improved outcomes in patients with heart failure, and REVIVED certainly has been conducted now in an era where at least some of these drugs are more systematically implemented.”

Rounding out this session are the Scottish ALL-HEART study of allopurinol in ischemic heart disease and EchoNet-RCT, looking at whether artificial intelligence (AI) can improve the accuracy of echocardiograms.

Hot Line 4 features DELIVER, a phase 3 trial of the SGLT2 inhibitor dapagliflozin (Farxiga) in HF with preserved or mildly reduced ejection fraction. Topline results, released in May, showed that the study has met its primary endpoint of cardiovascular death or worsening HF.

Dr. Windecker said DELIVER will be a “highlight” of the meeting, particularly because EMPEROR-Preserved, presented at ESC 2021, showed a benefit for another SGLT2 inhibitor, empagliflozin, in this very specific setting. Two prespecified analyses will also be presented, pooling data from EMPEROR-Preserved and from the DAPA-HF study of dapagliflozin in patients with reduced EF. “This will be a session very rich in terms of information.”

Another not-to-be-missed session is Hot Line 5, which will focus on antithrombotic therapy, according to Dr. Windecker, who will cochair the Sunday, Aug. 28 session.

First up is the investigator-initiated INVICTUS-VKA, testing rivaroxaban noninferiority versus standard vitamin K antagonists in patients with atrial fibrillation (AFib) and rheumatic heart disease, a setting in which non–vitamin K antagonists have not been sufficiently tested.

This is followed by three phase 2 trials – PACIFIC-AMI, PACIFIC-STROKE, and AXIOMATIC-SSP – investigating the novel factor XIa inhibitors BAY 2433334 and BMS-986177 in patients with myocardial infarction or stroke.
 

Hot Line sessions 6-10

Sunday’s Hot Line 6 takes another look at smartphone-based AFib screening in eBRAVE-HF, use of causal AI to improve the validity of cardiovascular risk prediction, and AI-enhanced detection of aortic stenosis.

Hot Line 7 rounds out the day, putting coronary imaging center stage. It includes perfusion scanning with MR or PET after a positive angiogram in DanNICAD-2, the PET tracer 18F-sodium fluoride as a marker of high-risk coronary plaques in patients with recent MIs in PREFFIR, and fractional flow reserve- versus angiography-guided PCI in acute MI with multivessel disease in FRAME-AMI.

After a weekend of top-notch science and, no doubt, a spot of revelry, the focus returns on Monday, Aug. 29 to three Hot Line sessions. The first of these, Hot Line 8, updates five clinical trials, including 5-year outcomes from ISCHEMIA-CKD EXTEND, 15-month results from MASTER DAPT, and primary results from FOURIER-OLE, the open-label extension study of evolocumab out to 5 years in approximately 1,600 study participants.

The session closes out with causes of mortality in the FIDELITY trial of finerenone and a win-ratio analysis of PARADISE-MI.

Hot Line 9, billed as an “evidence synthesis on clinically important questions,” includes a Cholesterol Treatment Trialists’ (CTT) Collaboration meta-analysis on the effects of statins on muscle symptoms and a meta-analysis of angiotensin-receptor blockers and beta-blockers in Marfan syndrome from the Marfan Treatment Trialists’ Collaboration.

Also featured is evidence on radial versus femoral access for coronary procedures, and PANTHER, a patient-level meta-analysis of aspirin or P2Y12 inhibitor monotherapy as secondary prevention in patients with established coronary artery disease.

COVID-19, deeply rooted in the minds of attendees and considered in 52 separate sessions, takes over the final Hot Line session of the Congress. Hot Line 10 will report on antithrombotic therapy in critically ill patients in COVID-PACT and on anti-inflammatory therapy with colchicine and antithrombotic therapy with aspirin alone or in combination with rivaroxaban in the ACT inpatient and outpatient trials. Although such early trials have been largely negative, the latest details will be interesting to see, Dr. Windecker suggested.

In terms of COVID-19 protocols, ESC will recommend but not mandate masks and will have test kits available should attendees wish to have a test or if they become symptomatic, he noted.
 

New guidelines released

Four new ESC guidelines will be released during the congress on cardio-oncology, ventricular arrhythmias and sudden cardiac death, pulmonary hypertension, and cardiovascular assessment and management of patients undergoing noncardiac surgery.

In addition to a guideline overview on Friday, one guideline will be featured each day in a 1-hour session, with additional time for discussions with guideline task force members, and six sessions devoted to the implementation of existing guidelines in clinical practice.

The ESC already has a position paper on cardio-oncology, but now, for the first time, has a full guideline with formal laws and level-of-evidence recommendations, Dr. Windecker pointed out.

“I think what will be the great asset, not only of the guideline but out of this emerging field, is that people in the future will probably not only be treated when it’s too late or suffer from toxicity but that there will be screening, and people will be aware before the implementation of therapy,” he added.

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

After 2 years of virtual gatherings, the annual European Society of Cardiology Congress 2022 is back and celebrating its 70th birthday live in the raucously beautiful city of Barcelona.

Much of the upcoming event, scheduled for Aug. 26 to 29, however, will also be broadcast online, and the full program will be available on-demand after the meeting.

The hybrid format is intentional, leveraging the social interaction that only live meetings can provide and the global reach of online access, Program Committee Chair Stephan Windecker, MD, Bern University Hospital, Switzerland, told this news organization.

“It enables a lot of people who, for some reason, cannot travel to still connect, and it also provides what we’ve done in the past, but I think in a more natural way of doing it,” he said. “You can connect later on again, read, digest, look at sessions that you may have missed, and that’s a nice experience to take advantage of.”

Thus far, early registrations are favoring the sunny climes, with about 14,000 onsite and 4,200 online attendees.

This year’s spotlight theme is cardiac imaging, with programming throughout the Congress devoted to its role in diagnosis, treatment, follow-up, and, increasingly, guidance of interventions.

“Particularly as it relates to the transcatheter heart valves, it’s really a new discipline, and I think you can’t overemphasize that enough, because the interventional result directly depends on the quality of imaging,” Dr. Windecker said. “This will certainly logarithmically increase during the next few years.”

The always highly anticipated Hot Line sessions mushroomed this year to 10, featuring 36 studies, up from just 4 sessions and 20 studies last year.

“Especially during the COVID pandemic, many investigators and trialists experienced difficulties in recruitment, difficulties in terms of also personnel shortages, and so on. So really, we feel very privileged at the large number of submissions,” he said. “I think there are really very interesting ones, which we tried to spread throughout the 4 days.”
 

Hot Line sessions 1-5

Among the studies Dr. Windecker highlighted is TIME, which kicks off Hot Line 1 on Friday, Aug. 26, and aimed to establish whether antihypertensive medications taken at night are truly more cardioprotective than those taken in the morning.

The topic has been hotly debated, with proponents pointing to a near halving of mortality and cardiovascular events with bedtime dosing in the Hygia Chronotherapy trial. Skeptics question the validity and conduct of the trial, however, prompting an investigation by the European Heart Journal, which found no evidence of misconduct but has many looking for more definitive data.

Also in this session is SECURE, pitting a cardiovascular polypill that contains aspirin, ramipril, and atorvastatin against usual care in secondary prevention, and PERSPECTIVE, comparing the effects of sacubitril/valsartan with valsartan on cognitive function in patients with chronic heart failure and preserved ejection fraction (HFpEF).

Hot Line 2, the first of three Hot Lines taking place on Saturday, Aug. 27, features the Danish cardiovascular screening trial DANCAVAS, the phase 4 ADVOR trial of acetazolamide (Diamox) in acute decompensated heart failure (HF), and the DANFLU-1 trial of high- versus standard-dose influenza vaccine in the elderly.

Also on tap is the BOX trial, comparing two blood pressure and two oxygenation targets in comatose out-of-hospital cardiac arrest patients.

“It addresses an understudied patient population, and the second element is that sometimes things you do out of ordinary application – so, the application of oxygen – may have beneficial but also adverse impact,” Dr. Windecker said. “So, to study this in a randomized clinical trial is really important.”

Additionally, he highlighted REVIVED, which will be presented in Hot Line 3 and is the first trial to examine percutaneous coronary intervention (PCI) with optimal medical therapy (OMT) versus OMT alone in the setting of severe ischemic cardiomyopathy.

“We have data from the STICH trial, where surgical revascularization was investigated in ischemic cardiomyopathy, but the open question is: What about PCI as revascularization?” Dr. Windecker said. “The other reason it’s interesting is that we have these evidence-based drugs that have dramatically improved outcomes in patients with heart failure, and REVIVED certainly has been conducted now in an era where at least some of these drugs are more systematically implemented.”

Rounding out this session are the Scottish ALL-HEART study of allopurinol in ischemic heart disease and EchoNet-RCT, looking at whether artificial intelligence (AI) can improve the accuracy of echocardiograms.

Hot Line 4 features DELIVER, a phase 3 trial of the SGLT2 inhibitor dapagliflozin (Farxiga) in HF with preserved or mildly reduced ejection fraction. Topline results, released in May, showed that the study has met its primary endpoint of cardiovascular death or worsening HF.

Dr. Windecker said DELIVER will be a “highlight” of the meeting, particularly because EMPEROR-Preserved, presented at ESC 2021, showed a benefit for another SGLT2 inhibitor, empagliflozin, in this very specific setting. Two prespecified analyses will also be presented, pooling data from EMPEROR-Preserved and from the DAPA-HF study of dapagliflozin in patients with reduced EF. “This will be a session very rich in terms of information.”

Another not-to-be-missed session is Hot Line 5, which will focus on antithrombotic therapy, according to Dr. Windecker, who will cochair the Sunday, Aug. 28 session.

First up is the investigator-initiated INVICTUS-VKA, testing rivaroxaban noninferiority versus standard vitamin K antagonists in patients with atrial fibrillation (AFib) and rheumatic heart disease, a setting in which non–vitamin K antagonists have not been sufficiently tested.

This is followed by three phase 2 trials – PACIFIC-AMI, PACIFIC-STROKE, and AXIOMATIC-SSP – investigating the novel factor XIa inhibitors BAY 2433334 and BMS-986177 in patients with myocardial infarction or stroke.
 

Hot Line sessions 6-10

Sunday’s Hot Line 6 takes another look at smartphone-based AFib screening in eBRAVE-HF, use of causal AI to improve the validity of cardiovascular risk prediction, and AI-enhanced detection of aortic stenosis.

Hot Line 7 rounds out the day, putting coronary imaging center stage. It includes perfusion scanning with MR or PET after a positive angiogram in DanNICAD-2, the PET tracer 18F-sodium fluoride as a marker of high-risk coronary plaques in patients with recent MIs in PREFFIR, and fractional flow reserve- versus angiography-guided PCI in acute MI with multivessel disease in FRAME-AMI.

After a weekend of top-notch science and, no doubt, a spot of revelry, the focus returns on Monday, Aug. 29 to three Hot Line sessions. The first of these, Hot Line 8, updates five clinical trials, including 5-year outcomes from ISCHEMIA-CKD EXTEND, 15-month results from MASTER DAPT, and primary results from FOURIER-OLE, the open-label extension study of evolocumab out to 5 years in approximately 1,600 study participants.

The session closes out with causes of mortality in the FIDELITY trial of finerenone and a win-ratio analysis of PARADISE-MI.

Hot Line 9, billed as an “evidence synthesis on clinically important questions,” includes a Cholesterol Treatment Trialists’ (CTT) Collaboration meta-analysis on the effects of statins on muscle symptoms and a meta-analysis of angiotensin-receptor blockers and beta-blockers in Marfan syndrome from the Marfan Treatment Trialists’ Collaboration.

Also featured is evidence on radial versus femoral access for coronary procedures, and PANTHER, a patient-level meta-analysis of aspirin or P2Y12 inhibitor monotherapy as secondary prevention in patients with established coronary artery disease.

COVID-19, deeply rooted in the minds of attendees and considered in 52 separate sessions, takes over the final Hot Line session of the Congress. Hot Line 10 will report on antithrombotic therapy in critically ill patients in COVID-PACT and on anti-inflammatory therapy with colchicine and antithrombotic therapy with aspirin alone or in combination with rivaroxaban in the ACT inpatient and outpatient trials. Although such early trials have been largely negative, the latest details will be interesting to see, Dr. Windecker suggested.

In terms of COVID-19 protocols, ESC will recommend but not mandate masks and will have test kits available should attendees wish to have a test or if they become symptomatic, he noted.
 

New guidelines released

Four new ESC guidelines will be released during the congress on cardio-oncology, ventricular arrhythmias and sudden cardiac death, pulmonary hypertension, and cardiovascular assessment and management of patients undergoing noncardiac surgery.

In addition to a guideline overview on Friday, one guideline will be featured each day in a 1-hour session, with additional time for discussions with guideline task force members, and six sessions devoted to the implementation of existing guidelines in clinical practice.

The ESC already has a position paper on cardio-oncology, but now, for the first time, has a full guideline with formal laws and level-of-evidence recommendations, Dr. Windecker pointed out.

“I think what will be the great asset, not only of the guideline but out of this emerging field, is that people in the future will probably not only be treated when it’s too late or suffer from toxicity but that there will be screening, and people will be aware before the implementation of therapy,” he added.

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

After 2 years of virtual gatherings, the annual European Society of Cardiology Congress 2022 is back and celebrating its 70th birthday live in the raucously beautiful city of Barcelona.

Much of the upcoming event, scheduled for Aug. 26 to 29, however, will also be broadcast online, and the full program will be available on-demand after the meeting.

The hybrid format is intentional, leveraging the social interaction that only live meetings can provide and the global reach of online access, Program Committee Chair Stephan Windecker, MD, Bern University Hospital, Switzerland, told this news organization.

“It enables a lot of people who, for some reason, cannot travel to still connect, and it also provides what we’ve done in the past, but I think in a more natural way of doing it,” he said. “You can connect later on again, read, digest, look at sessions that you may have missed, and that’s a nice experience to take advantage of.”

Thus far, early registrations are favoring the sunny climes, with about 14,000 onsite and 4,200 online attendees.

This year’s spotlight theme is cardiac imaging, with programming throughout the Congress devoted to its role in diagnosis, treatment, follow-up, and, increasingly, guidance of interventions.

“Particularly as it relates to the transcatheter heart valves, it’s really a new discipline, and I think you can’t overemphasize that enough, because the interventional result directly depends on the quality of imaging,” Dr. Windecker said. “This will certainly logarithmically increase during the next few years.”

The always highly anticipated Hot Line sessions mushroomed this year to 10, featuring 36 studies, up from just 4 sessions and 20 studies last year.

“Especially during the COVID pandemic, many investigators and trialists experienced difficulties in recruitment, difficulties in terms of also personnel shortages, and so on. So really, we feel very privileged at the large number of submissions,” he said. “I think there are really very interesting ones, which we tried to spread throughout the 4 days.”
 

Hot Line sessions 1-5

Among the studies Dr. Windecker highlighted is TIME, which kicks off Hot Line 1 on Friday, Aug. 26, and aimed to establish whether antihypertensive medications taken at night are truly more cardioprotective than those taken in the morning.

The topic has been hotly debated, with proponents pointing to a near halving of mortality and cardiovascular events with bedtime dosing in the Hygia Chronotherapy trial. Skeptics question the validity and conduct of the trial, however, prompting an investigation by the European Heart Journal, which found no evidence of misconduct but has many looking for more definitive data.

Also in this session is SECURE, pitting a cardiovascular polypill that contains aspirin, ramipril, and atorvastatin against usual care in secondary prevention, and PERSPECTIVE, comparing the effects of sacubitril/valsartan with valsartan on cognitive function in patients with chronic heart failure and preserved ejection fraction (HFpEF).

Hot Line 2, the first of three Hot Lines taking place on Saturday, Aug. 27, features the Danish cardiovascular screening trial DANCAVAS, the phase 4 ADVOR trial of acetazolamide (Diamox) in acute decompensated heart failure (HF), and the DANFLU-1 trial of high- versus standard-dose influenza vaccine in the elderly.

Also on tap is the BOX trial, comparing two blood pressure and two oxygenation targets in comatose out-of-hospital cardiac arrest patients.

“It addresses an understudied patient population, and the second element is that sometimes things you do out of ordinary application – so, the application of oxygen – may have beneficial but also adverse impact,” Dr. Windecker said. “So, to study this in a randomized clinical trial is really important.”

Additionally, he highlighted REVIVED, which will be presented in Hot Line 3 and is the first trial to examine percutaneous coronary intervention (PCI) with optimal medical therapy (OMT) versus OMT alone in the setting of severe ischemic cardiomyopathy.

“We have data from the STICH trial, where surgical revascularization was investigated in ischemic cardiomyopathy, but the open question is: What about PCI as revascularization?” Dr. Windecker said. “The other reason it’s interesting is that we have these evidence-based drugs that have dramatically improved outcomes in patients with heart failure, and REVIVED certainly has been conducted now in an era where at least some of these drugs are more systematically implemented.”

Rounding out this session are the Scottish ALL-HEART study of allopurinol in ischemic heart disease and EchoNet-RCT, looking at whether artificial intelligence (AI) can improve the accuracy of echocardiograms.

Hot Line 4 features DELIVER, a phase 3 trial of the SGLT2 inhibitor dapagliflozin (Farxiga) in HF with preserved or mildly reduced ejection fraction. Topline results, released in May, showed that the study has met its primary endpoint of cardiovascular death or worsening HF.

Dr. Windecker said DELIVER will be a “highlight” of the meeting, particularly because EMPEROR-Preserved, presented at ESC 2021, showed a benefit for another SGLT2 inhibitor, empagliflozin, in this very specific setting. Two prespecified analyses will also be presented, pooling data from EMPEROR-Preserved and from the DAPA-HF study of dapagliflozin in patients with reduced EF. “This will be a session very rich in terms of information.”

Another not-to-be-missed session is Hot Line 5, which will focus on antithrombotic therapy, according to Dr. Windecker, who will cochair the Sunday, Aug. 28 session.

First up is the investigator-initiated INVICTUS-VKA, testing rivaroxaban noninferiority versus standard vitamin K antagonists in patients with atrial fibrillation (AFib) and rheumatic heart disease, a setting in which non–vitamin K antagonists have not been sufficiently tested.

This is followed by three phase 2 trials – PACIFIC-AMI, PACIFIC-STROKE, and AXIOMATIC-SSP – investigating the novel factor XIa inhibitors BAY 2433334 and BMS-986177 in patients with myocardial infarction or stroke.
 

Hot Line sessions 6-10

Sunday’s Hot Line 6 takes another look at smartphone-based AFib screening in eBRAVE-HF, use of causal AI to improve the validity of cardiovascular risk prediction, and AI-enhanced detection of aortic stenosis.

Hot Line 7 rounds out the day, putting coronary imaging center stage. It includes perfusion scanning with MR or PET after a positive angiogram in DanNICAD-2, the PET tracer 18F-sodium fluoride as a marker of high-risk coronary plaques in patients with recent MIs in PREFFIR, and fractional flow reserve- versus angiography-guided PCI in acute MI with multivessel disease in FRAME-AMI.

After a weekend of top-notch science and, no doubt, a spot of revelry, the focus returns on Monday, Aug. 29 to three Hot Line sessions. The first of these, Hot Line 8, updates five clinical trials, including 5-year outcomes from ISCHEMIA-CKD EXTEND, 15-month results from MASTER DAPT, and primary results from FOURIER-OLE, the open-label extension study of evolocumab out to 5 years in approximately 1,600 study participants.

The session closes out with causes of mortality in the FIDELITY trial of finerenone and a win-ratio analysis of PARADISE-MI.

Hot Line 9, billed as an “evidence synthesis on clinically important questions,” includes a Cholesterol Treatment Trialists’ (CTT) Collaboration meta-analysis on the effects of statins on muscle symptoms and a meta-analysis of angiotensin-receptor blockers and beta-blockers in Marfan syndrome from the Marfan Treatment Trialists’ Collaboration.

Also featured is evidence on radial versus femoral access for coronary procedures, and PANTHER, a patient-level meta-analysis of aspirin or P2Y12 inhibitor monotherapy as secondary prevention in patients with established coronary artery disease.

COVID-19, deeply rooted in the minds of attendees and considered in 52 separate sessions, takes over the final Hot Line session of the Congress. Hot Line 10 will report on antithrombotic therapy in critically ill patients in COVID-PACT and on anti-inflammatory therapy with colchicine and antithrombotic therapy with aspirin alone or in combination with rivaroxaban in the ACT inpatient and outpatient trials. Although such early trials have been largely negative, the latest details will be interesting to see, Dr. Windecker suggested.

In terms of COVID-19 protocols, ESC will recommend but not mandate masks and will have test kits available should attendees wish to have a test or if they become symptomatic, he noted.
 

New guidelines released

Four new ESC guidelines will be released during the congress on cardio-oncology, ventricular arrhythmias and sudden cardiac death, pulmonary hypertension, and cardiovascular assessment and management of patients undergoing noncardiac surgery.

In addition to a guideline overview on Friday, one guideline will be featured each day in a 1-hour session, with additional time for discussions with guideline task force members, and six sessions devoted to the implementation of existing guidelines in clinical practice.

The ESC already has a position paper on cardio-oncology, but now, for the first time, has a full guideline with formal laws and level-of-evidence recommendations, Dr. Windecker pointed out.

“I think what will be the great asset, not only of the guideline but out of this emerging field, is that people in the future will probably not only be treated when it’s too late or suffer from toxicity but that there will be screening, and people will be aware before the implementation of therapy,” he added.

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

Adults aged 85 years and older who logged an hour or more of walking each week had a 40% reduced risk of all-cause mortality compared with less active peers, according to data from more than 7,000 individuals.

“Aging is accompanied by reduced physical activity and increased sedentary behavior, and reduced physical activity is associated with decreased life expectancy,” Moo-Nyun Jin, MD, of Inje University Sanggye Paik Hospital, Seoul, South Korea, said in an interview.

Reduced physical activity was especially likely in the elderly during the COVID-19 pandemic, he added.

oneinchpunch/Thinkstock

“Promoting walking may be a simple way to help older adults avoid inactivity and encourage an active lifestyle for all-cause and cardiovascular mortality risk reduction,” Dr. Jin said.

Although walking is generally an easy form of exercise for the older adult population, the specific benefit of walking on reducing mortality has not been well studied, according to Dr. Jin and colleagues.

For adults of any age, current guidelines recommend at least 150 minutes per week of moderate activity or 75 minutes per week of vigorous activity, but the amount of physical activity tends to decline with age, and activity recommendations are more difficult to meet, the authors wrote in a press release accompanying their study.

In the study, to be presented at the European Society of Cardiology Congress on Aug. 28 (Abstract 85643), the researchers reviewed data from 7,047 adults aged 85 years and older who participated in the Korean National Health Screening Program. The average age of the study population was 87 years, and 68% were women. Participants completed questionnaires about the amount of time spent in leisure time activities each week, including walking at a slow pace, moderate activity (such as cycling or brisk walking), and vigorous activity (such as running).

Those who walked at a slow pace for at least 1 hour per week had a 40% reduced risk of all-cause mortality and a 39% reduced risk of cardiovascular mortality, compared with inactive participants.

The proportions of participants who reported walking, moderate activity,­ and vigorous ­intensity physical activity were 42.5%, 14.7%, and 11.0%, respectively. Roughly one-third (33%) of those who reported slow walking each week also reported moderate or vigorous physical activity.

However, walking for 1 hour per week significantly reduced the risk for all-cause mortality and cardiovascular mortality among individuals who reported walking only, without other moderate or vigorous physical activity (hazard ratio, 0.50 and 0.46, respectively).

“Walking was linked with a lower likelihood of dying in older adults, regardless of whether or not they did any moderate to vigorous intensity physical activity,” Dr. Jin told this news organization. “Our study indicates that walking even just 1 hour every week is advantageous to those aged 85 years and older compared to being inactive.”

The hour of walking need not be in long bouts, 10 minutes each day will do, Dr. Jin added.

The participants were divided into five groups based on reported amount of weekly walking. More than half (57.5%) reported no slow walking, 8.5% walked less than 1 hour per week, 12.0% walked 1-2 hours, 8.7% walked 2-3 hours, and 13.3% walked more than 3 hours.

Although the study was limited by the reliance on self-reports, the results were strengthened by the large sample size and support the value of easy walking for adults aged 85 years and older compared to being inactive.

“Walking may present an opportunity for promoting physical activity among the elderly population, offering a simple way to avoid inactivity and increase physical activity,” said Dr. Jin. However, more research is needed to evaluate the association between mortality and walking by objective measurement of walking levels, using a device such as a smart watch, he noted.

 

Results are preliminary

“This is an observational study, not an experiment, so it means causality cannot be presumed,” said Maria Fiatarone Singh, MD, a geriatrician with a focus on exercise physiology at the University of Sydney, in an interview. “In other words, it is possible that diseases resulting in mortality prevented people from walking rather than the other way around,” she noted. The only published experimental study on exercise and mortality in older adults was conducted by Dr. Fiatarone Singh and colleagues in Norway. In that study, published in the British Medical Journal in 2020, high-intensity training programs were associated with reduced all-cause mortality compared with inactive controls and individuals who engaged in moderate intensity exercise.

The current study “would have needed to control for many factors related to mortality, such as cardiovascular disease, hypertension, diabetes, malnutrition, and dementia to see what residual benefit might be related to walking,” Dr. Fiatarone Singh said.

“Although walking seems easy and safe, in fact people who are frail, sarcopenic, osteoporotic, or have fallen are recommended to do resistance and balance training rather than walking, and add walking later when they are able to do it safely,” she emphasized.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Fiatarone Singh had no financial conflicts to disclose.

Adults aged 85 years and older who logged an hour or more of walking each week had a 40% reduced risk of all-cause mortality compared with less active peers, according to data from more than 7,000 individuals.

“Aging is accompanied by reduced physical activity and increased sedentary behavior, and reduced physical activity is associated with decreased life expectancy,” Moo-Nyun Jin, MD, of Inje University Sanggye Paik Hospital, Seoul, South Korea, said in an interview.

Reduced physical activity was especially likely in the elderly during the COVID-19 pandemic, he added.

oneinchpunch/Thinkstock

“Promoting walking may be a simple way to help older adults avoid inactivity and encourage an active lifestyle for all-cause and cardiovascular mortality risk reduction,” Dr. Jin said.

Although walking is generally an easy form of exercise for the older adult population, the specific benefit of walking on reducing mortality has not been well studied, according to Dr. Jin and colleagues.

For adults of any age, current guidelines recommend at least 150 minutes per week of moderate activity or 75 minutes per week of vigorous activity, but the amount of physical activity tends to decline with age, and activity recommendations are more difficult to meet, the authors wrote in a press release accompanying their study.

In the study, to be presented at the European Society of Cardiology Congress on Aug. 28 (Abstract 85643), the researchers reviewed data from 7,047 adults aged 85 years and older who participated in the Korean National Health Screening Program. The average age of the study population was 87 years, and 68% were women. Participants completed questionnaires about the amount of time spent in leisure time activities each week, including walking at a slow pace, moderate activity (such as cycling or brisk walking), and vigorous activity (such as running).

Those who walked at a slow pace for at least 1 hour per week had a 40% reduced risk of all-cause mortality and a 39% reduced risk of cardiovascular mortality, compared with inactive participants.

The proportions of participants who reported walking, moderate activity,­ and vigorous ­intensity physical activity were 42.5%, 14.7%, and 11.0%, respectively. Roughly one-third (33%) of those who reported slow walking each week also reported moderate or vigorous physical activity.

However, walking for 1 hour per week significantly reduced the risk for all-cause mortality and cardiovascular mortality among individuals who reported walking only, without other moderate or vigorous physical activity (hazard ratio, 0.50 and 0.46, respectively).

“Walking was linked with a lower likelihood of dying in older adults, regardless of whether or not they did any moderate to vigorous intensity physical activity,” Dr. Jin told this news organization. “Our study indicates that walking even just 1 hour every week is advantageous to those aged 85 years and older compared to being inactive.”

The hour of walking need not be in long bouts, 10 minutes each day will do, Dr. Jin added.

The participants were divided into five groups based on reported amount of weekly walking. More than half (57.5%) reported no slow walking, 8.5% walked less than 1 hour per week, 12.0% walked 1-2 hours, 8.7% walked 2-3 hours, and 13.3% walked more than 3 hours.

Although the study was limited by the reliance on self-reports, the results were strengthened by the large sample size and support the value of easy walking for adults aged 85 years and older compared to being inactive.

“Walking may present an opportunity for promoting physical activity among the elderly population, offering a simple way to avoid inactivity and increase physical activity,” said Dr. Jin. However, more research is needed to evaluate the association between mortality and walking by objective measurement of walking levels, using a device such as a smart watch, he noted.

 

Results are preliminary

“This is an observational study, not an experiment, so it means causality cannot be presumed,” said Maria Fiatarone Singh, MD, a geriatrician with a focus on exercise physiology at the University of Sydney, in an interview. “In other words, it is possible that diseases resulting in mortality prevented people from walking rather than the other way around,” she noted. The only published experimental study on exercise and mortality in older adults was conducted by Dr. Fiatarone Singh and colleagues in Norway. In that study, published in the British Medical Journal in 2020, high-intensity training programs were associated with reduced all-cause mortality compared with inactive controls and individuals who engaged in moderate intensity exercise.

The current study “would have needed to control for many factors related to mortality, such as cardiovascular disease, hypertension, diabetes, malnutrition, and dementia to see what residual benefit might be related to walking,” Dr. Fiatarone Singh said.

“Although walking seems easy and safe, in fact people who are frail, sarcopenic, osteoporotic, or have fallen are recommended to do resistance and balance training rather than walking, and add walking later when they are able to do it safely,” she emphasized.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Fiatarone Singh had no financial conflicts to disclose.

Adults aged 85 years and older who logged an hour or more of walking each week had a 40% reduced risk of all-cause mortality compared with less active peers, according to data from more than 7,000 individuals.

“Aging is accompanied by reduced physical activity and increased sedentary behavior, and reduced physical activity is associated with decreased life expectancy,” Moo-Nyun Jin, MD, of Inje University Sanggye Paik Hospital, Seoul, South Korea, said in an interview.

Reduced physical activity was especially likely in the elderly during the COVID-19 pandemic, he added.

oneinchpunch/Thinkstock

“Promoting walking may be a simple way to help older adults avoid inactivity and encourage an active lifestyle for all-cause and cardiovascular mortality risk reduction,” Dr. Jin said.

Although walking is generally an easy form of exercise for the older adult population, the specific benefit of walking on reducing mortality has not been well studied, according to Dr. Jin and colleagues.

For adults of any age, current guidelines recommend at least 150 minutes per week of moderate activity or 75 minutes per week of vigorous activity, but the amount of physical activity tends to decline with age, and activity recommendations are more difficult to meet, the authors wrote in a press release accompanying their study.

In the study, to be presented at the European Society of Cardiology Congress on Aug. 28 (Abstract 85643), the researchers reviewed data from 7,047 adults aged 85 years and older who participated in the Korean National Health Screening Program. The average age of the study population was 87 years, and 68% were women. Participants completed questionnaires about the amount of time spent in leisure time activities each week, including walking at a slow pace, moderate activity (such as cycling or brisk walking), and vigorous activity (such as running).

Those who walked at a slow pace for at least 1 hour per week had a 40% reduced risk of all-cause mortality and a 39% reduced risk of cardiovascular mortality, compared with inactive participants.

The proportions of participants who reported walking, moderate activity,­ and vigorous ­intensity physical activity were 42.5%, 14.7%, and 11.0%, respectively. Roughly one-third (33%) of those who reported slow walking each week also reported moderate or vigorous physical activity.

However, walking for 1 hour per week significantly reduced the risk for all-cause mortality and cardiovascular mortality among individuals who reported walking only, without other moderate or vigorous physical activity (hazard ratio, 0.50 and 0.46, respectively).

“Walking was linked with a lower likelihood of dying in older adults, regardless of whether or not they did any moderate to vigorous intensity physical activity,” Dr. Jin told this news organization. “Our study indicates that walking even just 1 hour every week is advantageous to those aged 85 years and older compared to being inactive.”

The hour of walking need not be in long bouts, 10 minutes each day will do, Dr. Jin added.

The participants were divided into five groups based on reported amount of weekly walking. More than half (57.5%) reported no slow walking, 8.5% walked less than 1 hour per week, 12.0% walked 1-2 hours, 8.7% walked 2-3 hours, and 13.3% walked more than 3 hours.

Although the study was limited by the reliance on self-reports, the results were strengthened by the large sample size and support the value of easy walking for adults aged 85 years and older compared to being inactive.

“Walking may present an opportunity for promoting physical activity among the elderly population, offering a simple way to avoid inactivity and increase physical activity,” said Dr. Jin. However, more research is needed to evaluate the association between mortality and walking by objective measurement of walking levels, using a device such as a smart watch, he noted.

 

Results are preliminary

“This is an observational study, not an experiment, so it means causality cannot be presumed,” said Maria Fiatarone Singh, MD, a geriatrician with a focus on exercise physiology at the University of Sydney, in an interview. “In other words, it is possible that diseases resulting in mortality prevented people from walking rather than the other way around,” she noted. The only published experimental study on exercise and mortality in older adults was conducted by Dr. Fiatarone Singh and colleagues in Norway. In that study, published in the British Medical Journal in 2020, high-intensity training programs were associated with reduced all-cause mortality compared with inactive controls and individuals who engaged in moderate intensity exercise.

The current study “would have needed to control for many factors related to mortality, such as cardiovascular disease, hypertension, diabetes, malnutrition, and dementia to see what residual benefit might be related to walking,” Dr. Fiatarone Singh said.

“Although walking seems easy and safe, in fact people who are frail, sarcopenic, osteoporotic, or have fallen are recommended to do resistance and balance training rather than walking, and add walking later when they are able to do it safely,” she emphasized.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Fiatarone Singh had no financial conflicts to disclose.

Cholesterol levels in American adults have improved over the previous decade, but a large cross-sectional analysis of more than 30,000 U.S. adults has found notable disparities in cholesterol control, particularly among Asian adults, lower lipid control rates among Black and other Hispanic adults compared to Whites, and no appreciable improvements for people taking statins.

“We found that total cholesterol improved significantly among U.S. adults from 2008 to 2018,” senior study author Rishi Wadhera, MD, of Beth Israel Deaconess Medical Center in Boston, said in an interview. “When we looked at rates of lipid control among adults treated with statins, we found no significant improvements from 2008 through 2018.”

He noted the patterns for lipid control were consistent for women and men, adding, “In contrast to all other racial and ethnic groups, Mexican American and Black adults did experience significant improvements in cholesterol control. Despite this progress, rates of cholesterol control still remained significantly lower in Black adults compared to White adults.”

The study analyzed lipid concentrations from 33,040 adults ages 20 and older from the National Health and Nutrition Examination Surveys (NHANES), using 2007-2008 as the baseline and 2017-2018 as the endpoint. With lipid control defined as total cholesterol of 200 mg/dL or less, the analysis showed that total cholesterol improved in the overall population from 197 to 189 mg/dL in that time (95% confidence interval, –12.2 to –4.9 mg/dL; P < .001).

The study analyzed lipid trends in several demographic categories. Age-adjusted total cholesterol for women improved significantly, from 199 to 192 mg/dL (95% confidence interval [CI], –11.6 to –3.6 mg/dL; P < .001), but improved slightly more for men, from 195 to 185 mg/dL (95% CI, –14 to –5.1 mg/dL; P < .001).

Overall, age-adjusted total cholesterol improved significantly for Blacks (–7.8 mg/dL), Mexican Americans (–11.3 mg/dL), other Hispanic adults (–8 mg/dL) and Whites (–8.8 mg/dL; P < .001 for all), but not for Asian adults, measured from 2011-2012 to 2017-2018: –.2 mg/dL (95% CI, –6.5 to 6.2 mg/dL; P = .9).

The study found that LDL cholesterol, on an age-adjusted basis, improved significantly overall, from 116 mg/dL in 2007-2008 to 111 mg/dL in 2017-2018 (95% CI, –8.3 to –1.4 mg/dL; P = .001). However, unlike total cholesterol, this improvement didn’t carry over to most ethnic groups. Mexican American adults (–8 mg/dL; P = .01) and Whites (–5.9 mg/dL; P = .001) showed significant improvements, but Asian, Black or other Hispanic adults didn’t.

The study also evaluated lipid control in people taking statins and found that, overall, it didn’t change significantly: from 78.5% in 2007-2008 to 79.5% in 2017-2018 (P = .27). Mexican American adults were the only ethnic group that showed significant improvement in lipid control, going from 73% in 2007-2008 to 86.5% in 2017-2018 (P = .008).

Disparities in lipid control

Women had notably lower lipid control rates than men, with an odds ratio of .52 in 2007-2010 (P < .001), with similar patterns found in 2011-2014 (OR, 0.48) and 2015-2018 (OR, 0.54, P < .001 for both).

Lipid control worsened over time for Black and other Hispanic adults compared to Whites. In 2007-2010, lipid control rates among the studied ethnic groups were similar, a trend that carried over to the 2011-2014 study interval and included Asian adults. However, in 2015-2018, Blacks had lower rates of lipid control compared to Whites (OR, 0.66; 95% CI, .47-.94; P = .03), as did other Hispanic adults (OR, 0.59; 95% CI, .37-.95; P = .04).

These disparities between sexes and ethnic groups warrant further investigation, Dr. Wadhera said. “We were surprised that women had significantly lower rates of cholesterol control than men,” he said. “We need to better understand whether gaps in care, such barriers in access, less frequent lab monitoring of cholesterol, or less intensive prescribing of important treatments, contribute to these differences.”

He called the lower lipid control rates in Black and Hispanic adults “concerning, especially because rates of heart attacks and strokes remain high in these groups. ... Efforts to identify gaps in care and increase and intensify medical therapy are needed, as treatment rates in these populations are low.”

While the study collected data before the COVID-19 pandemic, Dr. Wadhera acknowledged that the management of cardiovascular risk factors may have worsened because of it. “Monitoring cholesterol levels and control rates in the U.S. population as we emerge from the pandemic will be critically important,” he said.

In an accompanying editorial, Hermes Florez, MD, PhD, of the Medical University of South Carolina in Charleston, and colleagues called for adequately powered studies to further investigate the disparities in the Asian and Hispanic populations. “Worse rates of cholesterol control observed in women and in minority populations deserve special attention,” they wrote.

They noted that future studies should consider the impact of guidelines and recommendations that emerged since the study started, namely from the American College of Cardiology/American Heart Association 2013 guidelines, Healthy People 2030, and the U.S. Preventive Services Task Force (JAMA. 2022 Aug 23. doi: 10.1001/jama.2022.13044).

“More important, future work must focus on how to effectively eliminate those disparities and better control modifiable risk factors to enhance outcomes for all individuals regardless of race and ethnicity,” Dr. Florez and colleagues wrote.

The study received funding from the National Heart, Lung, and Blood Institute. Dr. Wadhera disclosed relationships with CVS Health and Abbott. Dr. Florez and colleagues have no disclosures.

Cholesterol levels in American adults have improved over the previous decade, but a large cross-sectional analysis of more than 30,000 U.S. adults has found notable disparities in cholesterol control, particularly among Asian adults, lower lipid control rates among Black and other Hispanic adults compared to Whites, and no appreciable improvements for people taking statins.

“We found that total cholesterol improved significantly among U.S. adults from 2008 to 2018,” senior study author Rishi Wadhera, MD, of Beth Israel Deaconess Medical Center in Boston, said in an interview. “When we looked at rates of lipid control among adults treated with statins, we found no significant improvements from 2008 through 2018.”

He noted the patterns for lipid control were consistent for women and men, adding, “In contrast to all other racial and ethnic groups, Mexican American and Black adults did experience significant improvements in cholesterol control. Despite this progress, rates of cholesterol control still remained significantly lower in Black adults compared to White adults.”

The study analyzed lipid concentrations from 33,040 adults ages 20 and older from the National Health and Nutrition Examination Surveys (NHANES), using 2007-2008 as the baseline and 2017-2018 as the endpoint. With lipid control defined as total cholesterol of 200 mg/dL or less, the analysis showed that total cholesterol improved in the overall population from 197 to 189 mg/dL in that time (95% confidence interval, –12.2 to –4.9 mg/dL; P < .001).

The study analyzed lipid trends in several demographic categories. Age-adjusted total cholesterol for women improved significantly, from 199 to 192 mg/dL (95% confidence interval [CI], –11.6 to –3.6 mg/dL; P < .001), but improved slightly more for men, from 195 to 185 mg/dL (95% CI, –14 to –5.1 mg/dL; P < .001).

Overall, age-adjusted total cholesterol improved significantly for Blacks (–7.8 mg/dL), Mexican Americans (–11.3 mg/dL), other Hispanic adults (–8 mg/dL) and Whites (–8.8 mg/dL; P < .001 for all), but not for Asian adults, measured from 2011-2012 to 2017-2018: –.2 mg/dL (95% CI, –6.5 to 6.2 mg/dL; P = .9).

The study found that LDL cholesterol, on an age-adjusted basis, improved significantly overall, from 116 mg/dL in 2007-2008 to 111 mg/dL in 2017-2018 (95% CI, –8.3 to –1.4 mg/dL; P = .001). However, unlike total cholesterol, this improvement didn’t carry over to most ethnic groups. Mexican American adults (–8 mg/dL; P = .01) and Whites (–5.9 mg/dL; P = .001) showed significant improvements, but Asian, Black or other Hispanic adults didn’t.

The study also evaluated lipid control in people taking statins and found that, overall, it didn’t change significantly: from 78.5% in 2007-2008 to 79.5% in 2017-2018 (P = .27). Mexican American adults were the only ethnic group that showed significant improvement in lipid control, going from 73% in 2007-2008 to 86.5% in 2017-2018 (P = .008).

Disparities in lipid control

Women had notably lower lipid control rates than men, with an odds ratio of .52 in 2007-2010 (P < .001), with similar patterns found in 2011-2014 (OR, 0.48) and 2015-2018 (OR, 0.54, P < .001 for both).

Lipid control worsened over time for Black and other Hispanic adults compared to Whites. In 2007-2010, lipid control rates among the studied ethnic groups were similar, a trend that carried over to the 2011-2014 study interval and included Asian adults. However, in 2015-2018, Blacks had lower rates of lipid control compared to Whites (OR, 0.66; 95% CI, .47-.94; P = .03), as did other Hispanic adults (OR, 0.59; 95% CI, .37-.95; P = .04).

These disparities between sexes and ethnic groups warrant further investigation, Dr. Wadhera said. “We were surprised that women had significantly lower rates of cholesterol control than men,” he said. “We need to better understand whether gaps in care, such barriers in access, less frequent lab monitoring of cholesterol, or less intensive prescribing of important treatments, contribute to these differences.”

He called the lower lipid control rates in Black and Hispanic adults “concerning, especially because rates of heart attacks and strokes remain high in these groups. ... Efforts to identify gaps in care and increase and intensify medical therapy are needed, as treatment rates in these populations are low.”

While the study collected data before the COVID-19 pandemic, Dr. Wadhera acknowledged that the management of cardiovascular risk factors may have worsened because of it. “Monitoring cholesterol levels and control rates in the U.S. population as we emerge from the pandemic will be critically important,” he said.

In an accompanying editorial, Hermes Florez, MD, PhD, of the Medical University of South Carolina in Charleston, and colleagues called for adequately powered studies to further investigate the disparities in the Asian and Hispanic populations. “Worse rates of cholesterol control observed in women and in minority populations deserve special attention,” they wrote.

They noted that future studies should consider the impact of guidelines and recommendations that emerged since the study started, namely from the American College of Cardiology/American Heart Association 2013 guidelines, Healthy People 2030, and the U.S. Preventive Services Task Force (JAMA. 2022 Aug 23. doi: 10.1001/jama.2022.13044).

“More important, future work must focus on how to effectively eliminate those disparities and better control modifiable risk factors to enhance outcomes for all individuals regardless of race and ethnicity,” Dr. Florez and colleagues wrote.

The study received funding from the National Heart, Lung, and Blood Institute. Dr. Wadhera disclosed relationships with CVS Health and Abbott. Dr. Florez and colleagues have no disclosures.

Cholesterol levels in American adults have improved over the previous decade, but a large cross-sectional analysis of more than 30,000 U.S. adults has found notable disparities in cholesterol control, particularly among Asian adults, lower lipid control rates among Black and other Hispanic adults compared to Whites, and no appreciable improvements for people taking statins.

“We found that total cholesterol improved significantly among U.S. adults from 2008 to 2018,” senior study author Rishi Wadhera, MD, of Beth Israel Deaconess Medical Center in Boston, said in an interview. “When we looked at rates of lipid control among adults treated with statins, we found no significant improvements from 2008 through 2018.”

He noted the patterns for lipid control were consistent for women and men, adding, “In contrast to all other racial and ethnic groups, Mexican American and Black adults did experience significant improvements in cholesterol control. Despite this progress, rates of cholesterol control still remained significantly lower in Black adults compared to White adults.”

The study analyzed lipid concentrations from 33,040 adults ages 20 and older from the National Health and Nutrition Examination Surveys (NHANES), using 2007-2008 as the baseline and 2017-2018 as the endpoint. With lipid control defined as total cholesterol of 200 mg/dL or less, the analysis showed that total cholesterol improved in the overall population from 197 to 189 mg/dL in that time (95% confidence interval, –12.2 to –4.9 mg/dL; P < .001).

The study analyzed lipid trends in several demographic categories. Age-adjusted total cholesterol for women improved significantly, from 199 to 192 mg/dL (95% confidence interval [CI], –11.6 to –3.6 mg/dL; P < .001), but improved slightly more for men, from 195 to 185 mg/dL (95% CI, –14 to –5.1 mg/dL; P < .001).

Overall, age-adjusted total cholesterol improved significantly for Blacks (–7.8 mg/dL), Mexican Americans (–11.3 mg/dL), other Hispanic adults (–8 mg/dL) and Whites (–8.8 mg/dL; P < .001 for all), but not for Asian adults, measured from 2011-2012 to 2017-2018: –.2 mg/dL (95% CI, –6.5 to 6.2 mg/dL; P = .9).

The study found that LDL cholesterol, on an age-adjusted basis, improved significantly overall, from 116 mg/dL in 2007-2008 to 111 mg/dL in 2017-2018 (95% CI, –8.3 to –1.4 mg/dL; P = .001). However, unlike total cholesterol, this improvement didn’t carry over to most ethnic groups. Mexican American adults (–8 mg/dL; P = .01) and Whites (–5.9 mg/dL; P = .001) showed significant improvements, but Asian, Black or other Hispanic adults didn’t.

The study also evaluated lipid control in people taking statins and found that, overall, it didn’t change significantly: from 78.5% in 2007-2008 to 79.5% in 2017-2018 (P = .27). Mexican American adults were the only ethnic group that showed significant improvement in lipid control, going from 73% in 2007-2008 to 86.5% in 2017-2018 (P = .008).

Disparities in lipid control

Women had notably lower lipid control rates than men, with an odds ratio of .52 in 2007-2010 (P < .001), with similar patterns found in 2011-2014 (OR, 0.48) and 2015-2018 (OR, 0.54, P < .001 for both).

Lipid control worsened over time for Black and other Hispanic adults compared to Whites. In 2007-2010, lipid control rates among the studied ethnic groups were similar, a trend that carried over to the 2011-2014 study interval and included Asian adults. However, in 2015-2018, Blacks had lower rates of lipid control compared to Whites (OR, 0.66; 95% CI, .47-.94; P = .03), as did other Hispanic adults (OR, 0.59; 95% CI, .37-.95; P = .04).

These disparities between sexes and ethnic groups warrant further investigation, Dr. Wadhera said. “We were surprised that women had significantly lower rates of cholesterol control than men,” he said. “We need to better understand whether gaps in care, such barriers in access, less frequent lab monitoring of cholesterol, or less intensive prescribing of important treatments, contribute to these differences.”

He called the lower lipid control rates in Black and Hispanic adults “concerning, especially because rates of heart attacks and strokes remain high in these groups. ... Efforts to identify gaps in care and increase and intensify medical therapy are needed, as treatment rates in these populations are low.”

While the study collected data before the COVID-19 pandemic, Dr. Wadhera acknowledged that the management of cardiovascular risk factors may have worsened because of it. “Monitoring cholesterol levels and control rates in the U.S. population as we emerge from the pandemic will be critically important,” he said.

In an accompanying editorial, Hermes Florez, MD, PhD, of the Medical University of South Carolina in Charleston, and colleagues called for adequately powered studies to further investigate the disparities in the Asian and Hispanic populations. “Worse rates of cholesterol control observed in women and in minority populations deserve special attention,” they wrote.

They noted that future studies should consider the impact of guidelines and recommendations that emerged since the study started, namely from the American College of Cardiology/American Heart Association 2013 guidelines, Healthy People 2030, and the U.S. Preventive Services Task Force (JAMA. 2022 Aug 23. doi: 10.1001/jama.2022.13044).

“More important, future work must focus on how to effectively eliminate those disparities and better control modifiable risk factors to enhance outcomes for all individuals regardless of race and ethnicity,” Dr. Florez and colleagues wrote.

The study received funding from the National Heart, Lung, and Blood Institute. Dr. Wadhera disclosed relationships with CVS Health and Abbott. Dr. Florez and colleagues have no disclosures.

A 5-minute bout of direct-to-consumer advertising (DTCA) for prescription heart drugs was associated with favorable perceptions of both medication use and pharmaceutical companies, but did not seem to negate intentions to use lifestyle interventions, a survey study shows.

Participants who watched ads for various prescription heart drugs, with or without price disclosure, were more likely to report positive perceptions of drug companies and intentions to take actions such as switching medications.

AlShadsky/Fotolia.com

The ads did not seem to affect intentions to eat healthfully and exercise.

The study was published online in JAMA Health Forum.
 

DTCA ‘unlikely to have an adverse effect’

“Increasing prevalence of DTCA may promote an overreliance on medication over healthy lifestyle choices to manage chronic conditions,” coauthor Yashaswini Singh, MPA, a PhD candidate at the Johns Hopkins University, Baltimore, told this news organization. “Thus, we hypothesized that DTCA exposure would reduce the likelihood of individuals engaging in preventive health behaviors.”

“However,” she said, “our results did not support this hypothesis, suggesting that exposure to DTCA for heart disease medication is unlikely to have an adverse effect on individuals’ intentions to engage in diet and exercise.”

That said, she added, “DTCA of prescription drugs can contribute to rising drug costs due to overprescribing of both inappropriate and brand-name drugs over cheaper generic alternatives. While we do not examine this mechanism in our paper, this remains an important question for future research.”

For the study, the team recruited 2,874 individuals (mean age, 53.8 years; 54% men; 83% White) from a U.S. nationally representative sample of people at high risk of cardiovascular disease, the Ipsos Public Affairs KnowledgePanel.

Participants were randomly assigned to one of three interventions: DTCA for heart disease medications, DTCA for heart disease medications with price disclosure, or nonpharmaceutical advertising (control). Each group watched five 1-minute videos for a total of 5 minutes of advertising exposure.

One group viewed ads for four heart disease medications – two ads for sacubitril/valsartan (Entresto, Novartis) and one each for rivaroxaban (Xarelto, Bayer), evolocumab (Repatha, Amgen), and ticagrelor (Brilinta, AstraZeneca); the second group saw the same ads, but with prices spliced in; and controls watched videos for nondrug products, such as consumer electronics.

Participants then completed a questionnaire to measure medication- and lifestyle-related intentions, as well as health-related beliefs and perceptions. Using a scale of 1 (highly unlikely) to 5 (highly likely), they rated the likelihood of their switching medication, asking a physician or insurer about a medication, searching for the drug online, or taking it as directed. The same scale was used to rate the likelihood of their being more physically active or eating more healthfully.

On a scale of 1 (always disagree) to 5 (always agree), they also related their perceptions of pharmaceutical manufacturers as being competent, innovative, and trustworthy.

To measure the magnitude of DTCA associations, the researchers calculated marginal effects (MEs) of treatment – that is, the difference in probability of an outcome between the treatment and control arms.

They found a positive association between DTCA and medication-related behavioral intentions, including intention to switch medication (ME, 0.004; P = .002) and engage in information-seeking behaviors (ME, 0.02; P = .01).

There was no evidence suggesting that pharmaceutical DTCA discouraged use of nonpharmacologic lifestyle interventions to help manage heart disease. DTCA also was positively associated with consumers’ favorable perceptions of pharmaceutical manufacturers (competence: ME, 0.03; P = .01; innovative: ME, 0.03; P = .008).

No differential associations were seen for price disclosures in DTCA.
 

Questions remain

The authors acknowledged that the study focused on short-term behavioral intentions and that “future research should focus on the long-term effects of advertising in a real-world randomized setting.”

Ms. Singh said additional questions, some of which her team is investigating, include “understanding the interaction between government policies [such as] drug pricing reforms and firms’ advertising decisions; understanding whether observed changes in individuals’ health beliefs translate into actual changes to information-seeking behavior and health care utilization; and whether the demographic, political, and social characteristics of individuals shape their behavioral responses to advertising.”

Johanna Contreras, MD, an advanced heart failure and transplantation cardiologist at Mount Sinai Hospital, New York, said in an interview that the findings don’t surprise her. “The caveat is that this study was an online survey, so it only captured the beliefs and intentions, but not patient demand for the product and use of the product.”

“I do believe DTCA can create positive intentions towards the product ... and could make people more receptive to interventions,” she said. However, the information must be presented in a balanced way.

In addition, she noted, “price is still important. I think people take pricing into account when deciding to proceed with an intervention. If the price is ‘right’ or a little lower than expected, then they will likely consider the product. But if the price is significantly lower, then they may not trust that it is a good product. Generic drugs are an example. Even though they are approved and far cheaper than brand names, patients are often skeptical to take them.”

The study was funded with a grant from the Blue Cross Blue Shield of Illinois Affordability Cures Consortium. Ms. Singh and coauthors disclosed no relevant financial relationships.

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

A 5-minute bout of direct-to-consumer advertising (DTCA) for prescription heart drugs was associated with favorable perceptions of both medication use and pharmaceutical companies, but did not seem to negate intentions to use lifestyle interventions, a survey study shows.

Participants who watched ads for various prescription heart drugs, with or without price disclosure, were more likely to report positive perceptions of drug companies and intentions to take actions such as switching medications.

AlShadsky/Fotolia.com

The ads did not seem to affect intentions to eat healthfully and exercise.

The study was published online in JAMA Health Forum.
 

DTCA ‘unlikely to have an adverse effect’

“Increasing prevalence of DTCA may promote an overreliance on medication over healthy lifestyle choices to manage chronic conditions,” coauthor Yashaswini Singh, MPA, a PhD candidate at the Johns Hopkins University, Baltimore, told this news organization. “Thus, we hypothesized that DTCA exposure would reduce the likelihood of individuals engaging in preventive health behaviors.”

“However,” she said, “our results did not support this hypothesis, suggesting that exposure to DTCA for heart disease medication is unlikely to have an adverse effect on individuals’ intentions to engage in diet and exercise.”

That said, she added, “DTCA of prescription drugs can contribute to rising drug costs due to overprescribing of both inappropriate and brand-name drugs over cheaper generic alternatives. While we do not examine this mechanism in our paper, this remains an important question for future research.”

For the study, the team recruited 2,874 individuals (mean age, 53.8 years; 54% men; 83% White) from a U.S. nationally representative sample of people at high risk of cardiovascular disease, the Ipsos Public Affairs KnowledgePanel.

Participants were randomly assigned to one of three interventions: DTCA for heart disease medications, DTCA for heart disease medications with price disclosure, or nonpharmaceutical advertising (control). Each group watched five 1-minute videos for a total of 5 minutes of advertising exposure.

One group viewed ads for four heart disease medications – two ads for sacubitril/valsartan (Entresto, Novartis) and one each for rivaroxaban (Xarelto, Bayer), evolocumab (Repatha, Amgen), and ticagrelor (Brilinta, AstraZeneca); the second group saw the same ads, but with prices spliced in; and controls watched videos for nondrug products, such as consumer electronics.

Participants then completed a questionnaire to measure medication- and lifestyle-related intentions, as well as health-related beliefs and perceptions. Using a scale of 1 (highly unlikely) to 5 (highly likely), they rated the likelihood of their switching medication, asking a physician or insurer about a medication, searching for the drug online, or taking it as directed. The same scale was used to rate the likelihood of their being more physically active or eating more healthfully.

On a scale of 1 (always disagree) to 5 (always agree), they also related their perceptions of pharmaceutical manufacturers as being competent, innovative, and trustworthy.

To measure the magnitude of DTCA associations, the researchers calculated marginal effects (MEs) of treatment – that is, the difference in probability of an outcome between the treatment and control arms.

They found a positive association between DTCA and medication-related behavioral intentions, including intention to switch medication (ME, 0.004; P = .002) and engage in information-seeking behaviors (ME, 0.02; P = .01).

There was no evidence suggesting that pharmaceutical DTCA discouraged use of nonpharmacologic lifestyle interventions to help manage heart disease. DTCA also was positively associated with consumers’ favorable perceptions of pharmaceutical manufacturers (competence: ME, 0.03; P = .01; innovative: ME, 0.03; P = .008).

No differential associations were seen for price disclosures in DTCA.
 

Questions remain

The authors acknowledged that the study focused on short-term behavioral intentions and that “future research should focus on the long-term effects of advertising in a real-world randomized setting.”

Ms. Singh said additional questions, some of which her team is investigating, include “understanding the interaction between government policies [such as] drug pricing reforms and firms’ advertising decisions; understanding whether observed changes in individuals’ health beliefs translate into actual changes to information-seeking behavior and health care utilization; and whether the demographic, political, and social characteristics of individuals shape their behavioral responses to advertising.”

Johanna Contreras, MD, an advanced heart failure and transplantation cardiologist at Mount Sinai Hospital, New York, said in an interview that the findings don’t surprise her. “The caveat is that this study was an online survey, so it only captured the beliefs and intentions, but not patient demand for the product and use of the product.”

“I do believe DTCA can create positive intentions towards the product ... and could make people more receptive to interventions,” she said. However, the information must be presented in a balanced way.

In addition, she noted, “price is still important. I think people take pricing into account when deciding to proceed with an intervention. If the price is ‘right’ or a little lower than expected, then they will likely consider the product. But if the price is significantly lower, then they may not trust that it is a good product. Generic drugs are an example. Even though they are approved and far cheaper than brand names, patients are often skeptical to take them.”

The study was funded with a grant from the Blue Cross Blue Shield of Illinois Affordability Cures Consortium. Ms. Singh and coauthors disclosed no relevant financial relationships.

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

A 5-minute bout of direct-to-consumer advertising (DTCA) for prescription heart drugs was associated with favorable perceptions of both medication use and pharmaceutical companies, but did not seem to negate intentions to use lifestyle interventions, a survey study shows.

Participants who watched ads for various prescription heart drugs, with or without price disclosure, were more likely to report positive perceptions of drug companies and intentions to take actions such as switching medications.

AlShadsky/Fotolia.com

The ads did not seem to affect intentions to eat healthfully and exercise.

The study was published online in JAMA Health Forum.
 

DTCA ‘unlikely to have an adverse effect’

“Increasing prevalence of DTCA may promote an overreliance on medication over healthy lifestyle choices to manage chronic conditions,” coauthor Yashaswini Singh, MPA, a PhD candidate at the Johns Hopkins University, Baltimore, told this news organization. “Thus, we hypothesized that DTCA exposure would reduce the likelihood of individuals engaging in preventive health behaviors.”

“However,” she said, “our results did not support this hypothesis, suggesting that exposure to DTCA for heart disease medication is unlikely to have an adverse effect on individuals’ intentions to engage in diet and exercise.”

That said, she added, “DTCA of prescription drugs can contribute to rising drug costs due to overprescribing of both inappropriate and brand-name drugs over cheaper generic alternatives. While we do not examine this mechanism in our paper, this remains an important question for future research.”

For the study, the team recruited 2,874 individuals (mean age, 53.8 years; 54% men; 83% White) from a U.S. nationally representative sample of people at high risk of cardiovascular disease, the Ipsos Public Affairs KnowledgePanel.

Participants were randomly assigned to one of three interventions: DTCA for heart disease medications, DTCA for heart disease medications with price disclosure, or nonpharmaceutical advertising (control). Each group watched five 1-minute videos for a total of 5 minutes of advertising exposure.

One group viewed ads for four heart disease medications – two ads for sacubitril/valsartan (Entresto, Novartis) and one each for rivaroxaban (Xarelto, Bayer), evolocumab (Repatha, Amgen), and ticagrelor (Brilinta, AstraZeneca); the second group saw the same ads, but with prices spliced in; and controls watched videos for nondrug products, such as consumer electronics.

Participants then completed a questionnaire to measure medication- and lifestyle-related intentions, as well as health-related beliefs and perceptions. Using a scale of 1 (highly unlikely) to 5 (highly likely), they rated the likelihood of their switching medication, asking a physician or insurer about a medication, searching for the drug online, or taking it as directed. The same scale was used to rate the likelihood of their being more physically active or eating more healthfully.

On a scale of 1 (always disagree) to 5 (always agree), they also related their perceptions of pharmaceutical manufacturers as being competent, innovative, and trustworthy.

To measure the magnitude of DTCA associations, the researchers calculated marginal effects (MEs) of treatment – that is, the difference in probability of an outcome between the treatment and control arms.

They found a positive association between DTCA and medication-related behavioral intentions, including intention to switch medication (ME, 0.004; P = .002) and engage in information-seeking behaviors (ME, 0.02; P = .01).

There was no evidence suggesting that pharmaceutical DTCA discouraged use of nonpharmacologic lifestyle interventions to help manage heart disease. DTCA also was positively associated with consumers’ favorable perceptions of pharmaceutical manufacturers (competence: ME, 0.03; P = .01; innovative: ME, 0.03; P = .008).

No differential associations were seen for price disclosures in DTCA.
 

Questions remain

The authors acknowledged that the study focused on short-term behavioral intentions and that “future research should focus on the long-term effects of advertising in a real-world randomized setting.”

Ms. Singh said additional questions, some of which her team is investigating, include “understanding the interaction between government policies [such as] drug pricing reforms and firms’ advertising decisions; understanding whether observed changes in individuals’ health beliefs translate into actual changes to information-seeking behavior and health care utilization; and whether the demographic, political, and social characteristics of individuals shape their behavioral responses to advertising.”

Johanna Contreras, MD, an advanced heart failure and transplantation cardiologist at Mount Sinai Hospital, New York, said in an interview that the findings don’t surprise her. “The caveat is that this study was an online survey, so it only captured the beliefs and intentions, but not patient demand for the product and use of the product.”

“I do believe DTCA can create positive intentions towards the product ... and could make people more receptive to interventions,” she said. However, the information must be presented in a balanced way.

In addition, she noted, “price is still important. I think people take pricing into account when deciding to proceed with an intervention. If the price is ‘right’ or a little lower than expected, then they will likely consider the product. But if the price is significantly lower, then they may not trust that it is a good product. Generic drugs are an example. Even though they are approved and far cheaper than brand names, patients are often skeptical to take them.”

The study was funded with a grant from the Blue Cross Blue Shield of Illinois Affordability Cures Consortium. Ms. Singh and coauthors disclosed no relevant financial relationships.

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