Cardiology

Adults older than 50 years who report experiencing persistently high levels of loneliness have a 56% increased risk for stroke, a new study showed.

The increased stroke risk did not apply to individuals who reported experiencing situational loneliness, a finding that investigators believe bolsters the hypothesis that chronic loneliness is driving the association.

“Our findings suggest that individuals who experience chronic loneliness are at higher risk for incident stroke,” lead investigator Yenee Soh, ScD, research associate of social and behavioral sciences in the Harvard T.H. Chan School of Public Health, Boston, told this news organization. “It is important to routinely assess loneliness, as the consequences may be worse if unidentified and/or ignored.”

The findings were published online in eClinicalMedicine.
 

Significant, Chronic Health Consequences

Exacerbated by the COVID-19 pandemic, loneliness is at an all-time high. A 2023 Surgeon General’s report highlighted the fact that loneliness and social isolation are linked to significant and chronic health consequences.

Previous research has linked loneliness to cardiovascular disease, yet few studies have examined the association between loneliness and stroke risk. The current study is one of the first to examine the association between changes in loneliness and stroke risk over time.

Using data from the 2006-2018 Health and Retirement Study, researchers assessed the link between loneliness and incident stroke over time. Between 2006 and 2008, 12,161 study participants, who were all older than 50 years with no history of stroke, responded to questions from the Revised UCLA Loneliness Scale. From these responses, researchers created summary loneliness scores.

Four years later, from 2010 to 2012, the 8936 remaining study participants responded to the same 20 questions again. Based on loneliness scores across the two time points, participants were divided into four groups:

• Consistently low (those who scored low on the loneliness scale at both baseline and follow-up).
• Remitting (those who scored high at baseline and low at follow-up).
• Recent onset (those who scored low at baseline and high at follow-up).
• Consistently high (those who scored high at both baseline and follow-up).

Incident stroke was determined by participant report and medical record data.

Among participants whose loneliness was measured at baseline only, 1237 strokes occurred during the 2006-2018 follow-up period. Among those who provided two loneliness assessments over time, 601 strokes occurred during the follow-up period.

Even after adjusting for social isolation, depressive symptoms, physical activity, body mass index, and other health conditions, investigators found that participants who reported being lonely at baseline only had a 25% increased stroke risk, compared with those who did not report being lonely at baseline (hazard ratio [HR], 1.25; 95% confidence interval (CI), 1.06-1.47).

Participants who reported having consistently high loneliness across both time points had a 56% increased risk for incident stroke vs those who did not report loneliness at both time points after adjusting for social isolation and depression (HR, 1.56; 95% CI, 1.11-2.18).

The researchers did not investigate any of the underlying issues that may contribute to the association between loneliness and stroke risk, but speculated there may be physiological factors at play. These could include inflammation caused by increased hypothalamic pituitary-adrenocortical activity, behavioral factors such as poor medication adherence, smoking and/or alcohol use, and psychosocial issues.

Those who experience chronic loneliness may represent individuals that are unable to develop or maintain satisfying social relationships, which may result in longer-term interpersonal difficulties, Dr. Soh noted.

“Since loneliness is a highly subjective experience, seeking help to address and intervene to address a patient’s specific personal needs is important. It’s important to distinguish loneliness from social isolation,” said Dr. Soh.

She added that “by screening for loneliness and providing care or referring patients to relevant behavioral healthcare providers, clinicians can play a crucial role in addressing loneliness and its associated health risks early on to help reduce the population burden of loneliness.”
 

Progressive Research

Commenting on the findings for this news organization, Elaine Jones, MD, medical director of Access TeleCare, who was not involved in the research, applauded the investigators for “advancing the topic by looking at the chronicity aspect of loneliness.”

She said more research is needed to investigate loneliness as a stroke risk factor and noted that there may be something inherently different among respondents who reported loneliness at both study time points.

“Personality types may play a role here. We know people with positive attitudes and outlooks can do better in challenging health situations than people who are negative in their attitudes, regardless of depression. Perhaps those who feel lonely initially decided to do something about it and join groups, take up a hobby, or re-engage with family or friends. Perhaps the people who are chronically lonely don’t, or can’t, do this,” Dr. Jones said.

Chronic loneliness can cause stress, she added, “and we know that stress chemicals and hormones can be harmful to health over long durations of time.”

The study was funded by the National Institute on Aging. There were no conflicts of interest noted.

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

Adults older than 50 years who report experiencing persistently high levels of loneliness have a 56% increased risk for stroke, a new study showed.

The increased stroke risk did not apply to individuals who reported experiencing situational loneliness, a finding that investigators believe bolsters the hypothesis that chronic loneliness is driving the association.

“Our findings suggest that individuals who experience chronic loneliness are at higher risk for incident stroke,” lead investigator Yenee Soh, ScD, research associate of social and behavioral sciences in the Harvard T.H. Chan School of Public Health, Boston, told this news organization. “It is important to routinely assess loneliness, as the consequences may be worse if unidentified and/or ignored.”

The findings were published online in eClinicalMedicine.
 

Significant, Chronic Health Consequences

Exacerbated by the COVID-19 pandemic, loneliness is at an all-time high. A 2023 Surgeon General’s report highlighted the fact that loneliness and social isolation are linked to significant and chronic health consequences.

Previous research has linked loneliness to cardiovascular disease, yet few studies have examined the association between loneliness and stroke risk. The current study is one of the first to examine the association between changes in loneliness and stroke risk over time.

Using data from the 2006-2018 Health and Retirement Study, researchers assessed the link between loneliness and incident stroke over time. Between 2006 and 2008, 12,161 study participants, who were all older than 50 years with no history of stroke, responded to questions from the Revised UCLA Loneliness Scale. From these responses, researchers created summary loneliness scores.

Four years later, from 2010 to 2012, the 8936 remaining study participants responded to the same 20 questions again. Based on loneliness scores across the two time points, participants were divided into four groups:

• Consistently low (those who scored low on the loneliness scale at both baseline and follow-up).
• Remitting (those who scored high at baseline and low at follow-up).
• Recent onset (those who scored low at baseline and high at follow-up).
• Consistently high (those who scored high at both baseline and follow-up).

Incident stroke was determined by participant report and medical record data.

Among participants whose loneliness was measured at baseline only, 1237 strokes occurred during the 2006-2018 follow-up period. Among those who provided two loneliness assessments over time, 601 strokes occurred during the follow-up period.

Even after adjusting for social isolation, depressive symptoms, physical activity, body mass index, and other health conditions, investigators found that participants who reported being lonely at baseline only had a 25% increased stroke risk, compared with those who did not report being lonely at baseline (hazard ratio [HR], 1.25; 95% confidence interval (CI), 1.06-1.47).

Participants who reported having consistently high loneliness across both time points had a 56% increased risk for incident stroke vs those who did not report loneliness at both time points after adjusting for social isolation and depression (HR, 1.56; 95% CI, 1.11-2.18).

The researchers did not investigate any of the underlying issues that may contribute to the association between loneliness and stroke risk, but speculated there may be physiological factors at play. These could include inflammation caused by increased hypothalamic pituitary-adrenocortical activity, behavioral factors such as poor medication adherence, smoking and/or alcohol use, and psychosocial issues.

Those who experience chronic loneliness may represent individuals that are unable to develop or maintain satisfying social relationships, which may result in longer-term interpersonal difficulties, Dr. Soh noted.

“Since loneliness is a highly subjective experience, seeking help to address and intervene to address a patient’s specific personal needs is important. It’s important to distinguish loneliness from social isolation,” said Dr. Soh.

She added that “by screening for loneliness and providing care or referring patients to relevant behavioral healthcare providers, clinicians can play a crucial role in addressing loneliness and its associated health risks early on to help reduce the population burden of loneliness.”
 

Progressive Research

Commenting on the findings for this news organization, Elaine Jones, MD, medical director of Access TeleCare, who was not involved in the research, applauded the investigators for “advancing the topic by looking at the chronicity aspect of loneliness.”

She said more research is needed to investigate loneliness as a stroke risk factor and noted that there may be something inherently different among respondents who reported loneliness at both study time points.

“Personality types may play a role here. We know people with positive attitudes and outlooks can do better in challenging health situations than people who are negative in their attitudes, regardless of depression. Perhaps those who feel lonely initially decided to do something about it and join groups, take up a hobby, or re-engage with family or friends. Perhaps the people who are chronically lonely don’t, or can’t, do this,” Dr. Jones said.

Chronic loneliness can cause stress, she added, “and we know that stress chemicals and hormones can be harmful to health over long durations of time.”

The study was funded by the National Institute on Aging. There were no conflicts of interest noted.

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

Adults older than 50 years who report experiencing persistently high levels of loneliness have a 56% increased risk for stroke, a new study showed.

The increased stroke risk did not apply to individuals who reported experiencing situational loneliness, a finding that investigators believe bolsters the hypothesis that chronic loneliness is driving the association.

“Our findings suggest that individuals who experience chronic loneliness are at higher risk for incident stroke,” lead investigator Yenee Soh, ScD, research associate of social and behavioral sciences in the Harvard T.H. Chan School of Public Health, Boston, told this news organization. “It is important to routinely assess loneliness, as the consequences may be worse if unidentified and/or ignored.”

The findings were published online in eClinicalMedicine.
 

Significant, Chronic Health Consequences

Exacerbated by the COVID-19 pandemic, loneliness is at an all-time high. A 2023 Surgeon General’s report highlighted the fact that loneliness and social isolation are linked to significant and chronic health consequences.

Previous research has linked loneliness to cardiovascular disease, yet few studies have examined the association between loneliness and stroke risk. The current study is one of the first to examine the association between changes in loneliness and stroke risk over time.

Using data from the 2006-2018 Health and Retirement Study, researchers assessed the link between loneliness and incident stroke over time. Between 2006 and 2008, 12,161 study participants, who were all older than 50 years with no history of stroke, responded to questions from the Revised UCLA Loneliness Scale. From these responses, researchers created summary loneliness scores.

Four years later, from 2010 to 2012, the 8936 remaining study participants responded to the same 20 questions again. Based on loneliness scores across the two time points, participants were divided into four groups:

• Consistently low (those who scored low on the loneliness scale at both baseline and follow-up).
• Remitting (those who scored high at baseline and low at follow-up).
• Recent onset (those who scored low at baseline and high at follow-up).
• Consistently high (those who scored high at both baseline and follow-up).

Incident stroke was determined by participant report and medical record data.

Among participants whose loneliness was measured at baseline only, 1237 strokes occurred during the 2006-2018 follow-up period. Among those who provided two loneliness assessments over time, 601 strokes occurred during the follow-up period.

Even after adjusting for social isolation, depressive symptoms, physical activity, body mass index, and other health conditions, investigators found that participants who reported being lonely at baseline only had a 25% increased stroke risk, compared with those who did not report being lonely at baseline (hazard ratio [HR], 1.25; 95% confidence interval (CI), 1.06-1.47).

Participants who reported having consistently high loneliness across both time points had a 56% increased risk for incident stroke vs those who did not report loneliness at both time points after adjusting for social isolation and depression (HR, 1.56; 95% CI, 1.11-2.18).

The researchers did not investigate any of the underlying issues that may contribute to the association between loneliness and stroke risk, but speculated there may be physiological factors at play. These could include inflammation caused by increased hypothalamic pituitary-adrenocortical activity, behavioral factors such as poor medication adherence, smoking and/or alcohol use, and psychosocial issues.

Those who experience chronic loneliness may represent individuals that are unable to develop or maintain satisfying social relationships, which may result in longer-term interpersonal difficulties, Dr. Soh noted.

“Since loneliness is a highly subjective experience, seeking help to address and intervene to address a patient’s specific personal needs is important. It’s important to distinguish loneliness from social isolation,” said Dr. Soh.

She added that “by screening for loneliness and providing care or referring patients to relevant behavioral healthcare providers, clinicians can play a crucial role in addressing loneliness and its associated health risks early on to help reduce the population burden of loneliness.”
 

Progressive Research

Commenting on the findings for this news organization, Elaine Jones, MD, medical director of Access TeleCare, who was not involved in the research, applauded the investigators for “advancing the topic by looking at the chronicity aspect of loneliness.”

She said more research is needed to investigate loneliness as a stroke risk factor and noted that there may be something inherently different among respondents who reported loneliness at both study time points.

“Personality types may play a role here. We know people with positive attitudes and outlooks can do better in challenging health situations than people who are negative in their attitudes, regardless of depression. Perhaps those who feel lonely initially decided to do something about it and join groups, take up a hobby, or re-engage with family or friends. Perhaps the people who are chronically lonely don’t, or can’t, do this,” Dr. Jones said.

Chronic loneliness can cause stress, she added, “and we know that stress chemicals and hormones can be harmful to health over long durations of time.”

The study was funded by the National Institute on Aging. There were no conflicts of interest noted.

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

TOPLINE:

A new analysis showed that preeclampsia is associated with an increased risk for young-onset dementia.

METHODOLOGY:

• Researchers analyzed data from the French Conception study, a nationwide prospective cohort study of more than 1.9 million pregnancies.
• Mothers were followed for an average of 9 years.

TAKEAWAY:

• Nearly 3% of the mothers had preeclampsia, and 128 developed young-onset dementia.
• Preeclampsia was associated with a 2.65-fold increased risk for young-onset dementia after adjusting for obesity, diabetes, smoking, drug or alcohol addiction, and social deprivation.
• The risk was greater when preeclampsia occurred before 34 weeks of gestation (hazard ratio [HR], 4.15) or was superimposed on chronic hypertension (HR, 4.76).
• Prior research has found an association between preeclampsia and vascular dementia, but this analysis “is the first to show an increase in early-onset dementia risk,” the authors of the study wrote.

IN PRACTICE:

“Individuals who have had preeclampsia should be reassured that young-onset dementia remains a very rare condition. Their absolute risk increases only imperceptibly,” Stephen Tong, PhD, and Roxanne Hastie, PhD, both with the University of Melbourne, Melbourne, Australia, wrote in a related commentary about the findings.

“Individuals who have been affected by preeclampsia in a prior pregnancy might instead focus on reducing their risk of developing the many chronic health ailments that are far more common,” they added. “Although it is yet to be proven in clinical trials, it is plausible that after an episode of preeclampsia, adopting a healthy lifestyle may improve vascular health and reduce the risk of many serious cardiovascular conditions.”

SOURCE:

Valérie Olié, PhD, of the Santé Publique France in Saint-Maurice, France, was the corresponding author on the paper. The research letter was published online in JAMA Network Open.

LIMITATIONS:

The investigators relied on hospital records to identify cases of dementia, which may have led to underestimation of incidence of the disease.

DISCLOSURES:

The study was funded by the French Hypertension Society, the French Hypertension Research Foundation, and the French Cardiology Federation. A co-author disclosed personal fees from pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

A new analysis showed that preeclampsia is associated with an increased risk for young-onset dementia.

METHODOLOGY:

• Researchers analyzed data from the French Conception study, a nationwide prospective cohort study of more than 1.9 million pregnancies.
• Mothers were followed for an average of 9 years.

TAKEAWAY:

• Nearly 3% of the mothers had preeclampsia, and 128 developed young-onset dementia.
• Preeclampsia was associated with a 2.65-fold increased risk for young-onset dementia after adjusting for obesity, diabetes, smoking, drug or alcohol addiction, and social deprivation.
• The risk was greater when preeclampsia occurred before 34 weeks of gestation (hazard ratio [HR], 4.15) or was superimposed on chronic hypertension (HR, 4.76).
• Prior research has found an association between preeclampsia and vascular dementia, but this analysis “is the first to show an increase in early-onset dementia risk,” the authors of the study wrote.

IN PRACTICE:

“Individuals who have had preeclampsia should be reassured that young-onset dementia remains a very rare condition. Their absolute risk increases only imperceptibly,” Stephen Tong, PhD, and Roxanne Hastie, PhD, both with the University of Melbourne, Melbourne, Australia, wrote in a related commentary about the findings.

“Individuals who have been affected by preeclampsia in a prior pregnancy might instead focus on reducing their risk of developing the many chronic health ailments that are far more common,” they added. “Although it is yet to be proven in clinical trials, it is plausible that after an episode of preeclampsia, adopting a healthy lifestyle may improve vascular health and reduce the risk of many serious cardiovascular conditions.”

SOURCE:

Valérie Olié, PhD, of the Santé Publique France in Saint-Maurice, France, was the corresponding author on the paper. The research letter was published online in JAMA Network Open.

LIMITATIONS:

The investigators relied on hospital records to identify cases of dementia, which may have led to underestimation of incidence of the disease.

DISCLOSURES:

The study was funded by the French Hypertension Society, the French Hypertension Research Foundation, and the French Cardiology Federation. A co-author disclosed personal fees from pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

A new analysis showed that preeclampsia is associated with an increased risk for young-onset dementia.

METHODOLOGY:

• Researchers analyzed data from the French Conception study, a nationwide prospective cohort study of more than 1.9 million pregnancies.
• Mothers were followed for an average of 9 years.

TAKEAWAY:

• Nearly 3% of the mothers had preeclampsia, and 128 developed young-onset dementia.
• Preeclampsia was associated with a 2.65-fold increased risk for young-onset dementia after adjusting for obesity, diabetes, smoking, drug or alcohol addiction, and social deprivation.
• The risk was greater when preeclampsia occurred before 34 weeks of gestation (hazard ratio [HR], 4.15) or was superimposed on chronic hypertension (HR, 4.76).
• Prior research has found an association between preeclampsia and vascular dementia, but this analysis “is the first to show an increase in early-onset dementia risk,” the authors of the study wrote.

IN PRACTICE:

“Individuals who have had preeclampsia should be reassured that young-onset dementia remains a very rare condition. Their absolute risk increases only imperceptibly,” Stephen Tong, PhD, and Roxanne Hastie, PhD, both with the University of Melbourne, Melbourne, Australia, wrote in a related commentary about the findings.

“Individuals who have been affected by preeclampsia in a prior pregnancy might instead focus on reducing their risk of developing the many chronic health ailments that are far more common,” they added. “Although it is yet to be proven in clinical trials, it is plausible that after an episode of preeclampsia, adopting a healthy lifestyle may improve vascular health and reduce the risk of many serious cardiovascular conditions.”

SOURCE:

Valérie Olié, PhD, of the Santé Publique France in Saint-Maurice, France, was the corresponding author on the paper. The research letter was published online in JAMA Network Open.

LIMITATIONS:

The investigators relied on hospital records to identify cases of dementia, which may have led to underestimation of incidence of the disease.

DISCLOSURES:

The study was funded by the French Hypertension Society, the French Hypertension Research Foundation, and the French Cardiology Federation. A co-author disclosed personal fees from pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Glucagon-like peptide 1 (GLP-1) receptor agonists such as semaglutide (marketed as Ozempic and Rybelsus for type 2 diabetes and as Wegovy for obesity) slow down digestion and curb hunger by working on the brain’s dopamine reward center. They are prescribed to promote weight loss, metabolic health in type 2 diabetes, and heart health in coronary artery disease.

Semaglutide can be prescribed in two forms: the brand-name version, which is approved and confirmed as safe and effective by the US Food and Drug Administration (FDA), and the versions that can be obtained from a compounding pharmacy. Compounding pharmacies are permitted by the FDA to produce what is “ essentially a copy” of approved medications when there’s an official shortage, which is currently the case with semaglutide and other GLP-1 receptor agonists.

Patients are often drawn to compounding pharmacies for pricing-related reasons. If semaglutide is prescribed for a clear indication like diabetes and is covered by insurance, the brand-name version is commonly dispensed. However, if it’s not covered, patients need to pay out of pocket for branded versions, which carry a monthly cost of $1000 or more. Alternatively, their doctors can prescribe compounded semaglutide, which some telehealth companies advertise at costs of approximately $150-$300 per month.
 

Potential Issues With Compounded Semaglutide 

Compounding pharmacies produce drugs from raw materials containing active pharmaceutical ingredients (APIs). Although compounders use many of the same ingredients found in brand-name medications, for drugs like semaglutide, they may opt for specific salts that are not identical to those involved in the production of the standard versions. These salts are typically reserved for research purposes and may not be suitable for general use.

In late 2023, the FDA issued a letter asking the public to exercise caution when using compounded products containing semaglutide or semaglutide salts. This was followed in January 2024 by an FDA communication citing adverse events reported with the use of compounded semaglutide and advising patients to avoid these versions if an approved form of the drug is available.
 

Compound Pharmacies: A Closer Look 

Compounding pharmacies have exploded in popularity in the past several decades. The compounding pharmacy market is expected to grow at 7.8% per year over the next decade. 

Historically, compounding pharmacies have filled a niche for specialty vitamins for intravenous administration as well as chemotherapy medications. They also offer controlled substances, such as ketamine lozenges and nasal sprays, which are unavailable or are in short supply from traditional manufacturers.

Compounding pharmacies fall into two categories. First are compounding pharmacies covered under Section 503A of the Federal Food, Drug and Cosmetic Act; these drugs are neither tested nor monitored. Such facilities do not have to report adverse events to the FDA. The second category is Section 503B outsourcing facilities. These pharmacies choose to be tested by, to be inspected by, and to report adverse events to the FDA. 
 

The FDA’s Latest Update on This Issue

This news organization contacted the FDA for an update on the adverse events reported about compounded semaglutide. From August 8, 2021, to March 31, 2024, they received more than 20,000 adverse events reports for FDA-approved semaglutide. Comparatively, there were 210 adverse events reported on compounded semaglutide products. 

The FDA went on to describe that many of the adverse events reported were consistent with known reactions in the labeling, like nausea, diarrhea, and headache. Yet, they added that, “the FDA is unable to determine how, or if, other factors may have contributed to these adverse events, such as differences in ingredients and formulation between FDA-approved and compounded semaglutide products.” They also noted there was variation in the data quality in the reports they have received, which came only from 503B compounding pharmacies.

In conclusion, given the concerns about compounded semaglutide, it is prudent for the prescribing physicians as well as the patients taking the medication to know that risks are “higher” according to the FDA. We eagerly await more specific information from the FDA to better understand reported adverse events. 
 

How to Help Patients Receive Safe Compounded Semaglutide 

For clinicians considering prescribing semaglutide from compounding pharmacies, there are several questions worth asking, according to the Alliance for Pharmacy Compounding. First, find out whether the pharmacy complies with United States Pharmacopeia compounding standards and whether they source their APIs from FDA-registered facilities, the latter being required by federal law. It’s also important to ensure that these facilities undergo periodic third-party testing to verify medication purity and dosing. 

Ask whether the pharmacy is accredited by the Pharmacy Compounding Accreditation Board (PCAB). Accreditation from the PCAB means that pharmacies have been assessed for processes related to continuous quality improvement. In addition, ask whether the pharmacy is designated as a 503B compounder and if not, why.

Finally, interviewing the pharmacist themselves can provide useful information about staffing, training, and their methods of preparing medications. For example, if they are preparing a sterile eye drop, it is important to ask about sterility testing.

Jesse M. Pines, MD, MBA, MSCE, is a clinical professor of emergency medicine at George Washington University in Washington, and a professor in the department of emergency medicine at Drexel University College of Medicine in Philadelphia, Pennsylvania. Dr. Pines is also the chief of clinical innovation at US Acute Care Solutions in Canton, Ohio. Robert D. Glatter, MD, is an assistant professor of emergency medicine at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. Dr. Pines reported conflicts of interest with CSL Behring and Abbott Point-of-Care. Dr. Glatter reported no relevant conflicts of interest.
 

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

Glucagon-like peptide 1 (GLP-1) receptor agonists such as semaglutide (marketed as Ozempic and Rybelsus for type 2 diabetes and as Wegovy for obesity) slow down digestion and curb hunger by working on the brain’s dopamine reward center. They are prescribed to promote weight loss, metabolic health in type 2 diabetes, and heart health in coronary artery disease.

Semaglutide can be prescribed in two forms: the brand-name version, which is approved and confirmed as safe and effective by the US Food and Drug Administration (FDA), and the versions that can be obtained from a compounding pharmacy. Compounding pharmacies are permitted by the FDA to produce what is “ essentially a copy” of approved medications when there’s an official shortage, which is currently the case with semaglutide and other GLP-1 receptor agonists.

Patients are often drawn to compounding pharmacies for pricing-related reasons. If semaglutide is prescribed for a clear indication like diabetes and is covered by insurance, the brand-name version is commonly dispensed. However, if it’s not covered, patients need to pay out of pocket for branded versions, which carry a monthly cost of $1000 or more. Alternatively, their doctors can prescribe compounded semaglutide, which some telehealth companies advertise at costs of approximately $150-$300 per month.
 

Potential Issues With Compounded Semaglutide 

Compounding pharmacies produce drugs from raw materials containing active pharmaceutical ingredients (APIs). Although compounders use many of the same ingredients found in brand-name medications, for drugs like semaglutide, they may opt for specific salts that are not identical to those involved in the production of the standard versions. These salts are typically reserved for research purposes and may not be suitable for general use.

In late 2023, the FDA issued a letter asking the public to exercise caution when using compounded products containing semaglutide or semaglutide salts. This was followed in January 2024 by an FDA communication citing adverse events reported with the use of compounded semaglutide and advising patients to avoid these versions if an approved form of the drug is available.
 

Compound Pharmacies: A Closer Look 

Compounding pharmacies have exploded in popularity in the past several decades. The compounding pharmacy market is expected to grow at 7.8% per year over the next decade. 

Historically, compounding pharmacies have filled a niche for specialty vitamins for intravenous administration as well as chemotherapy medications. They also offer controlled substances, such as ketamine lozenges and nasal sprays, which are unavailable or are in short supply from traditional manufacturers.

Compounding pharmacies fall into two categories. First are compounding pharmacies covered under Section 503A of the Federal Food, Drug and Cosmetic Act; these drugs are neither tested nor monitored. Such facilities do not have to report adverse events to the FDA. The second category is Section 503B outsourcing facilities. These pharmacies choose to be tested by, to be inspected by, and to report adverse events to the FDA. 
 

The FDA’s Latest Update on This Issue

This news organization contacted the FDA for an update on the adverse events reported about compounded semaglutide. From August 8, 2021, to March 31, 2024, they received more than 20,000 adverse events reports for FDA-approved semaglutide. Comparatively, there were 210 adverse events reported on compounded semaglutide products. 

The FDA went on to describe that many of the adverse events reported were consistent with known reactions in the labeling, like nausea, diarrhea, and headache. Yet, they added that, “the FDA is unable to determine how, or if, other factors may have contributed to these adverse events, such as differences in ingredients and formulation between FDA-approved and compounded semaglutide products.” They also noted there was variation in the data quality in the reports they have received, which came only from 503B compounding pharmacies.

In conclusion, given the concerns about compounded semaglutide, it is prudent for the prescribing physicians as well as the patients taking the medication to know that risks are “higher” according to the FDA. We eagerly await more specific information from the FDA to better understand reported adverse events. 
 

How to Help Patients Receive Safe Compounded Semaglutide 

For clinicians considering prescribing semaglutide from compounding pharmacies, there are several questions worth asking, according to the Alliance for Pharmacy Compounding. First, find out whether the pharmacy complies with United States Pharmacopeia compounding standards and whether they source their APIs from FDA-registered facilities, the latter being required by federal law. It’s also important to ensure that these facilities undergo periodic third-party testing to verify medication purity and dosing. 

Ask whether the pharmacy is accredited by the Pharmacy Compounding Accreditation Board (PCAB). Accreditation from the PCAB means that pharmacies have been assessed for processes related to continuous quality improvement. In addition, ask whether the pharmacy is designated as a 503B compounder and if not, why.

Finally, interviewing the pharmacist themselves can provide useful information about staffing, training, and their methods of preparing medications. For example, if they are preparing a sterile eye drop, it is important to ask about sterility testing.

Jesse M. Pines, MD, MBA, MSCE, is a clinical professor of emergency medicine at George Washington University in Washington, and a professor in the department of emergency medicine at Drexel University College of Medicine in Philadelphia, Pennsylvania. Dr. Pines is also the chief of clinical innovation at US Acute Care Solutions in Canton, Ohio. Robert D. Glatter, MD, is an assistant professor of emergency medicine at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. Dr. Pines reported conflicts of interest with CSL Behring and Abbott Point-of-Care. Dr. Glatter reported no relevant conflicts of interest.
 

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

Glucagon-like peptide 1 (GLP-1) receptor agonists such as semaglutide (marketed as Ozempic and Rybelsus for type 2 diabetes and as Wegovy for obesity) slow down digestion and curb hunger by working on the brain’s dopamine reward center. They are prescribed to promote weight loss, metabolic health in type 2 diabetes, and heart health in coronary artery disease.

Semaglutide can be prescribed in two forms: the brand-name version, which is approved and confirmed as safe and effective by the US Food and Drug Administration (FDA), and the versions that can be obtained from a compounding pharmacy. Compounding pharmacies are permitted by the FDA to produce what is “ essentially a copy” of approved medications when there’s an official shortage, which is currently the case with semaglutide and other GLP-1 receptor agonists.

Patients are often drawn to compounding pharmacies for pricing-related reasons. If semaglutide is prescribed for a clear indication like diabetes and is covered by insurance, the brand-name version is commonly dispensed. However, if it’s not covered, patients need to pay out of pocket for branded versions, which carry a monthly cost of $1000 or more. Alternatively, their doctors can prescribe compounded semaglutide, which some telehealth companies advertise at costs of approximately $150-$300 per month.
 

Potential Issues With Compounded Semaglutide 

Compounding pharmacies produce drugs from raw materials containing active pharmaceutical ingredients (APIs). Although compounders use many of the same ingredients found in brand-name medications, for drugs like semaglutide, they may opt for specific salts that are not identical to those involved in the production of the standard versions. These salts are typically reserved for research purposes and may not be suitable for general use.

In late 2023, the FDA issued a letter asking the public to exercise caution when using compounded products containing semaglutide or semaglutide salts. This was followed in January 2024 by an FDA communication citing adverse events reported with the use of compounded semaglutide and advising patients to avoid these versions if an approved form of the drug is available.
 

Compound Pharmacies: A Closer Look 

Compounding pharmacies have exploded in popularity in the past several decades. The compounding pharmacy market is expected to grow at 7.8% per year over the next decade. 

Historically, compounding pharmacies have filled a niche for specialty vitamins for intravenous administration as well as chemotherapy medications. They also offer controlled substances, such as ketamine lozenges and nasal sprays, which are unavailable or are in short supply from traditional manufacturers.

Compounding pharmacies fall into two categories. First are compounding pharmacies covered under Section 503A of the Federal Food, Drug and Cosmetic Act; these drugs are neither tested nor monitored. Such facilities do not have to report adverse events to the FDA. The second category is Section 503B outsourcing facilities. These pharmacies choose to be tested by, to be inspected by, and to report adverse events to the FDA. 
 

The FDA’s Latest Update on This Issue

This news organization contacted the FDA for an update on the adverse events reported about compounded semaglutide. From August 8, 2021, to March 31, 2024, they received more than 20,000 adverse events reports for FDA-approved semaglutide. Comparatively, there were 210 adverse events reported on compounded semaglutide products. 

The FDA went on to describe that many of the adverse events reported were consistent with known reactions in the labeling, like nausea, diarrhea, and headache. Yet, they added that, “the FDA is unable to determine how, or if, other factors may have contributed to these adverse events, such as differences in ingredients and formulation between FDA-approved and compounded semaglutide products.” They also noted there was variation in the data quality in the reports they have received, which came only from 503B compounding pharmacies.

In conclusion, given the concerns about compounded semaglutide, it is prudent for the prescribing physicians as well as the patients taking the medication to know that risks are “higher” according to the FDA. We eagerly await more specific information from the FDA to better understand reported adverse events. 
 

How to Help Patients Receive Safe Compounded Semaglutide 

For clinicians considering prescribing semaglutide from compounding pharmacies, there are several questions worth asking, according to the Alliance for Pharmacy Compounding. First, find out whether the pharmacy complies with United States Pharmacopeia compounding standards and whether they source their APIs from FDA-registered facilities, the latter being required by federal law. It’s also important to ensure that these facilities undergo periodic third-party testing to verify medication purity and dosing. 

Ask whether the pharmacy is accredited by the Pharmacy Compounding Accreditation Board (PCAB). Accreditation from the PCAB means that pharmacies have been assessed for processes related to continuous quality improvement. In addition, ask whether the pharmacy is designated as a 503B compounder and if not, why.

Finally, interviewing the pharmacist themselves can provide useful information about staffing, training, and their methods of preparing medications. For example, if they are preparing a sterile eye drop, it is important to ask about sterility testing.

Jesse M. Pines, MD, MBA, MSCE, is a clinical professor of emergency medicine at George Washington University in Washington, and a professor in the department of emergency medicine at Drexel University College of Medicine in Philadelphia, Pennsylvania. Dr. Pines is also the chief of clinical innovation at US Acute Care Solutions in Canton, Ohio. Robert D. Glatter, MD, is an assistant professor of emergency medicine at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. Dr. Pines reported conflicts of interest with CSL Behring and Abbott Point-of-Care. Dr. Glatter reported no relevant conflicts of interest.
 

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

Akira Endo, PhD, the Japanese microbiologist and biochemist known as the father of statins, died at the age of 90 on June 5. His research led to the discovery and rise of a class of drugs that revolutionized the prevention and treatment of cardiovascular diseases. This scientific journey began over half a century ago.

Inspired by Alexander Fleming

Born into a family of farmers in northern Japan, Dr. Endo was fascinated by natural sciences from a young age and showed a particular interest in fungi and molds. At the age of 10, he already knew he wanted to become a scientist.

He studied in Japan and the United States, conducting research at the Albert Einstein College of Medicine in New York City. He was struck by the high number of elderly and overweight individuals in the United States and realized the importance of developing a drug to combat cholesterol. It was upon his return to Japan, when he joined the Sankyo laboratory, that the development of statins began.

Inspired by Alexander Fleming, who discovered penicillin in the mold Penicillium, he hypothesized that fungi could produce antibiotics inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the enzyme that produces cholesterol precursors.

After a year of research on nearly 3800 strains, his team found a known substance, citrinin, that strongly inhibited HMG-CoA reductase and lowered serum cholesterol levels in rats. The research was halted because of its toxicity to the rodents’ kidneys. “Nevertheless, the experience with citrinin gave us hope and courage to quickly discover much more effective active substances,” said Dr. Endo in an article dedicated to the discovery of statins.
 

First Statin Discovered

In the summer of 1972, researchers discovered a second active culture broth, Penicillium citrinum Pen-51, which was isolated from a sample of rice collected in a grain store in Kyoto.

In July 1973, they isolated three active metabolites from this mold, one of which was compactin, which had structural similarities to HMG-CoA, the substrate of the HMG-CoA reductase reaction.

In 1976, they published two articles reporting the discovery and characterization of compactin (mevastatin), the first statin.
 

Several Setbacks

Unfortunately, when Sankyo biologists assessed the effectiveness of compactin by giving rats a diet supplemented with compactin for 7 days, no reduction in serum cholesterol was observed.

Only later did an unpublished study show that the statin significantly decreased plasma cholesterol after a month of treatment in laying hens. The hypocholesterolemic effects of compactin were then demonstrated in dogs and monkeys.

However, researchers faced a second challenge in April 1977. Microcrystalline structures were detected in the liver cells of rats that had been fed extremely high amounts of compactin (over 500 mg/kg per day for 5 weeks). Initially deemed toxic, the structures were ultimately found to be nontoxic.

A phase 2 trial began in the summer of 1979 with very encouraging preliminary results, but in August 1980, clinical development of compactin was halted, as the drug was suspected of causing lymphomas in dogs given very high doses: 100 or 200 mg/kg per day for 2 years.

This suspicion also led to the termination of trials on another statin, the closely related lovastatin, which was discovered simultaneously from different fungi by the Merck laboratory and Dr. Endo in February 1979.
 

First Statin Marketed

Subsequently, dramatic reductions in cholesterol levels observed in patients prompted Merck to conduct large-scale clinical trials of lovastatin in high-risk patients and long-term toxicity studies in dogs in 1984.

It was confirmed that the drug significantly reduced cholesterol levels and was well tolerated. No tumors were detected.

Lovastatin received approval from the Food and Drug Administration to become the first marketed statin in September 1987.

Dr. Endo received numerous awards for his work, including the Albert Lasker Award for Clinical Medical Research in 2008 and the Outstanding Achievement Award from the International Atherosclerosis Society in 2009.

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

Akira Endo, PhD, the Japanese microbiologist and biochemist known as the father of statins, died at the age of 90 on June 5. His research led to the discovery and rise of a class of drugs that revolutionized the prevention and treatment of cardiovascular diseases. This scientific journey began over half a century ago.

Inspired by Alexander Fleming

Born into a family of farmers in northern Japan, Dr. Endo was fascinated by natural sciences from a young age and showed a particular interest in fungi and molds. At the age of 10, he already knew he wanted to become a scientist.

He studied in Japan and the United States, conducting research at the Albert Einstein College of Medicine in New York City. He was struck by the high number of elderly and overweight individuals in the United States and realized the importance of developing a drug to combat cholesterol. It was upon his return to Japan, when he joined the Sankyo laboratory, that the development of statins began.

Inspired by Alexander Fleming, who discovered penicillin in the mold Penicillium, he hypothesized that fungi could produce antibiotics inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the enzyme that produces cholesterol precursors.

After a year of research on nearly 3800 strains, his team found a known substance, citrinin, that strongly inhibited HMG-CoA reductase and lowered serum cholesterol levels in rats. The research was halted because of its toxicity to the rodents’ kidneys. “Nevertheless, the experience with citrinin gave us hope and courage to quickly discover much more effective active substances,” said Dr. Endo in an article dedicated to the discovery of statins.
 

First Statin Discovered

In the summer of 1972, researchers discovered a second active culture broth, Penicillium citrinum Pen-51, which was isolated from a sample of rice collected in a grain store in Kyoto.

In July 1973, they isolated three active metabolites from this mold, one of which was compactin, which had structural similarities to HMG-CoA, the substrate of the HMG-CoA reductase reaction.

In 1976, they published two articles reporting the discovery and characterization of compactin (mevastatin), the first statin.
 

Several Setbacks

Unfortunately, when Sankyo biologists assessed the effectiveness of compactin by giving rats a diet supplemented with compactin for 7 days, no reduction in serum cholesterol was observed.

Only later did an unpublished study show that the statin significantly decreased plasma cholesterol after a month of treatment in laying hens. The hypocholesterolemic effects of compactin were then demonstrated in dogs and monkeys.

However, researchers faced a second challenge in April 1977. Microcrystalline structures were detected in the liver cells of rats that had been fed extremely high amounts of compactin (over 500 mg/kg per day for 5 weeks). Initially deemed toxic, the structures were ultimately found to be nontoxic.

A phase 2 trial began in the summer of 1979 with very encouraging preliminary results, but in August 1980, clinical development of compactin was halted, as the drug was suspected of causing lymphomas in dogs given very high doses: 100 or 200 mg/kg per day for 2 years.

This suspicion also led to the termination of trials on another statin, the closely related lovastatin, which was discovered simultaneously from different fungi by the Merck laboratory and Dr. Endo in February 1979.
 

First Statin Marketed

Subsequently, dramatic reductions in cholesterol levels observed in patients prompted Merck to conduct large-scale clinical trials of lovastatin in high-risk patients and long-term toxicity studies in dogs in 1984.

It was confirmed that the drug significantly reduced cholesterol levels and was well tolerated. No tumors were detected.

Lovastatin received approval from the Food and Drug Administration to become the first marketed statin in September 1987.

Dr. Endo received numerous awards for his work, including the Albert Lasker Award for Clinical Medical Research in 2008 and the Outstanding Achievement Award from the International Atherosclerosis Society in 2009.

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

Akira Endo, PhD, the Japanese microbiologist and biochemist known as the father of statins, died at the age of 90 on June 5. His research led to the discovery and rise of a class of drugs that revolutionized the prevention and treatment of cardiovascular diseases. This scientific journey began over half a century ago.

Inspired by Alexander Fleming

Born into a family of farmers in northern Japan, Dr. Endo was fascinated by natural sciences from a young age and showed a particular interest in fungi and molds. At the age of 10, he already knew he wanted to become a scientist.

He studied in Japan and the United States, conducting research at the Albert Einstein College of Medicine in New York City. He was struck by the high number of elderly and overweight individuals in the United States and realized the importance of developing a drug to combat cholesterol. It was upon his return to Japan, when he joined the Sankyo laboratory, that the development of statins began.

Inspired by Alexander Fleming, who discovered penicillin in the mold Penicillium, he hypothesized that fungi could produce antibiotics inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the enzyme that produces cholesterol precursors.

After a year of research on nearly 3800 strains, his team found a known substance, citrinin, that strongly inhibited HMG-CoA reductase and lowered serum cholesterol levels in rats. The research was halted because of its toxicity to the rodents’ kidneys. “Nevertheless, the experience with citrinin gave us hope and courage to quickly discover much more effective active substances,” said Dr. Endo in an article dedicated to the discovery of statins.
 

First Statin Discovered

In the summer of 1972, researchers discovered a second active culture broth, Penicillium citrinum Pen-51, which was isolated from a sample of rice collected in a grain store in Kyoto.

In July 1973, they isolated three active metabolites from this mold, one of which was compactin, which had structural similarities to HMG-CoA, the substrate of the HMG-CoA reductase reaction.

In 1976, they published two articles reporting the discovery and characterization of compactin (mevastatin), the first statin.
 

Several Setbacks

Unfortunately, when Sankyo biologists assessed the effectiveness of compactin by giving rats a diet supplemented with compactin for 7 days, no reduction in serum cholesterol was observed.

Only later did an unpublished study show that the statin significantly decreased plasma cholesterol after a month of treatment in laying hens. The hypocholesterolemic effects of compactin were then demonstrated in dogs and monkeys.

However, researchers faced a second challenge in April 1977. Microcrystalline structures were detected in the liver cells of rats that had been fed extremely high amounts of compactin (over 500 mg/kg per day for 5 weeks). Initially deemed toxic, the structures were ultimately found to be nontoxic.

A phase 2 trial began in the summer of 1979 with very encouraging preliminary results, but in August 1980, clinical development of compactin was halted, as the drug was suspected of causing lymphomas in dogs given very high doses: 100 or 200 mg/kg per day for 2 years.

This suspicion also led to the termination of trials on another statin, the closely related lovastatin, which was discovered simultaneously from different fungi by the Merck laboratory and Dr. Endo in February 1979.
 

First Statin Marketed

Subsequently, dramatic reductions in cholesterol levels observed in patients prompted Merck to conduct large-scale clinical trials of lovastatin in high-risk patients and long-term toxicity studies in dogs in 1984.

It was confirmed that the drug significantly reduced cholesterol levels and was well tolerated. No tumors were detected.

Lovastatin received approval from the Food and Drug Administration to become the first marketed statin in September 1987.

Dr. Endo received numerous awards for his work, including the Albert Lasker Award for Clinical Medical Research in 2008 and the Outstanding Achievement Award from the International Atherosclerosis Society in 2009.

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

Patients with atopic dermatitis (AD) had a lower risk for major adverse cardiovascular events (MACE) than the general population, and this risk was significantly lower than that of patients with rheumatoid arthritis (RA), according to an analysis of national claims data.

The results of the analysis were presented during a poster session at the Revolutionizing Atopic Dermatitis conference in Chicago. “While it is known that atopic dermatitis is associated with some comorbidities, the specific risk of major adverse cardiovascular events in patients with AD, especially those with moderate to severe AD within the US population, is unclear,” the study’s first author Christopher G. Bunick, MD, PhD, said in an interview following the conference.

To characterize the risk for MACE in patients with AD vs matched controls without AD (non-AD) and patients with RA, Dr. Bunick, associate professor of dermatology at Yale University, New Haven, Connecticut, and colleagues retrospectively evaluated US claims data from Optum’s Clinformatics Data Mart. The study population consisted of 381,221 patients aged 18 years and older who were diagnosed with AD from March 2017 to March 2023. Comparator groups included 381,221 non-AD controls matched by age, sex, and cohort entry, and 97,445 patients diagnosed with RA based on at least two claims for RA ≥ 7 days apart.

Patients were classified as having moderate to severe disease if they received dupilumab for AD or advanced systemic therapy for RA at any time during the follow-up period. The matched moderate to severe AD and non-AD cohorts were composed of 7134 patients each. The incidence of MACE was defined as inpatient hospitalization with myocardial infarction or stroke. The researchers used multivariable Cox proportional hazard models adjusted for baseline demographics, comorbidities, and medications to calculate the relative risk for MACE.
 

MACE Incidence, Relative Risk

The mean age of the AD cohort and non-AD matched controls was 58 years, and the mean age of the RA cohort was 67 years. The incidence of MACE per 100 patient-years was 1.78 among patients with AD, 1.83 among non-AD matched controls, and 2.12 among patients with RA. Patients with moderate to severe AD had a MACE incidence of 1.18 per 100 patient-years, which was lower than that of non-AD matched controls (1.52) and patients with moderate to severe RA (1.67).

In other findings, the relative risk for MACE in patients with AD was lower vs non-AD controls (adjusted hazard ratio [aHR], 0.91; 95% CI, 0.89-0.93; P < .001) and patients with RA (aHR, 0.83; 95% CI, 0.80-0.85; P < .001). Among patients with moderate to severe AD, MACE risk was similar to that of non-AD matched controls (aHR, 0.92; 95% CI, 0.73-1.14) and lower vs those with moderate to severe RA (aHR, 0.83; 95% CI, 0.73-0.94; P < .01).

MACE risk associated with AD was greater in patients who were older (per year, aHR, 1.05; 95% CI, 1.05-1.05), male (aHR, 0.81; 95% CI, 0.79-0.84), and Black vs White (aHR, 1.16; 95% CI, 1.11-1.21), and among those who received systemic corticosteroids in the 3 months before diagnosis (aHR, 1.10; 95% CI, 1.06-1.14), were hospitalized in the year before diagnosis (aHR, 1.35; 95% CI, 1.30-1.41), and had a history of smoking (aHR, 1.20; 95% CI, 1.16-1.24) and drug abuse (aHR, 1.34; 95% CI, 1.25-1.43).
 

Unexpected Results

“One surprising finding was that the incidence of MACE in patients with moderate to severe AD was actually lower than that in non-AD matched controls and significantly lower compared to patients with moderate to severe RA,” Dr. Bunick said. “This contrasts with the expectation that increased systemic inflammation in moderate to severe AD would correspond with a higher incidence of MACE.”

Another unexpected result, he said, was that, among patients with moderate to severe AD, the risk for MACE was not significantly different from that of non-AD matched controls, suggesting that the inflammatory burden in AD might not translate to as high a cardiovascular risk as previously assumed.

Dr. Bunick noted that advanced treatments for AD such as Janus kinase (JAK) inhibitors (upadacitinib and abrocitinib) have a class boxed warning for MACE based on a study of another JAK inhibitor (tofacitinib) in patients with RA, but “this may not apply to AD because patients with AD have a lower risk for MACE.”

In his opinion, he said, the study “underscores the importance of understanding the specific risks associated with different inflammatory conditions.” Moreover, “it emphasizes the potential benefits of newer systemic therapies in potentially mitigating cardiovascular risks in patients with moderate to severe AD.”

Dr. Bunick acknowledged certain limitations of the study, including its retrospective design and reliance on administrative claims data, which “may introduce coding errors and misclassification,” and the generalizability of the results, which may be limited to the US population.

AbbVie funded the study, and three of the coauthors are employees of the company. Dr. Bunick disclosed that he has served as an investigator and/or a consultant for AbbVie, Almirall, Apogee, Arcutis Biotherapeutics, Connect Biopharma, Daiichi Sankyo, EPI Health/Novan, LEO, Lilly, Novartis, Ortho Dermatologics, Palvella Therapeutics, Pfizer, Sanofi Regeneron, Sun, Takeda, Timber, and UCB.

A version of this article appeared on Medscape.com.

Patients with atopic dermatitis (AD) had a lower risk for major adverse cardiovascular events (MACE) than the general population, and this risk was significantly lower than that of patients with rheumatoid arthritis (RA), according to an analysis of national claims data.

The results of the analysis were presented during a poster session at the Revolutionizing Atopic Dermatitis conference in Chicago. “While it is known that atopic dermatitis is associated with some comorbidities, the specific risk of major adverse cardiovascular events in patients with AD, especially those with moderate to severe AD within the US population, is unclear,” the study’s first author Christopher G. Bunick, MD, PhD, said in an interview following the conference.

To characterize the risk for MACE in patients with AD vs matched controls without AD (non-AD) and patients with RA, Dr. Bunick, associate professor of dermatology at Yale University, New Haven, Connecticut, and colleagues retrospectively evaluated US claims data from Optum’s Clinformatics Data Mart. The study population consisted of 381,221 patients aged 18 years and older who were diagnosed with AD from March 2017 to March 2023. Comparator groups included 381,221 non-AD controls matched by age, sex, and cohort entry, and 97,445 patients diagnosed with RA based on at least two claims for RA ≥ 7 days apart.

Patients were classified as having moderate to severe disease if they received dupilumab for AD or advanced systemic therapy for RA at any time during the follow-up period. The matched moderate to severe AD and non-AD cohorts were composed of 7134 patients each. The incidence of MACE was defined as inpatient hospitalization with myocardial infarction or stroke. The researchers used multivariable Cox proportional hazard models adjusted for baseline demographics, comorbidities, and medications to calculate the relative risk for MACE.
 

MACE Incidence, Relative Risk

The mean age of the AD cohort and non-AD matched controls was 58 years, and the mean age of the RA cohort was 67 years. The incidence of MACE per 100 patient-years was 1.78 among patients with AD, 1.83 among non-AD matched controls, and 2.12 among patients with RA. Patients with moderate to severe AD had a MACE incidence of 1.18 per 100 patient-years, which was lower than that of non-AD matched controls (1.52) and patients with moderate to severe RA (1.67).

In other findings, the relative risk for MACE in patients with AD was lower vs non-AD controls (adjusted hazard ratio [aHR], 0.91; 95% CI, 0.89-0.93; P < .001) and patients with RA (aHR, 0.83; 95% CI, 0.80-0.85; P < .001). Among patients with moderate to severe AD, MACE risk was similar to that of non-AD matched controls (aHR, 0.92; 95% CI, 0.73-1.14) and lower vs those with moderate to severe RA (aHR, 0.83; 95% CI, 0.73-0.94; P < .01).

MACE risk associated with AD was greater in patients who were older (per year, aHR, 1.05; 95% CI, 1.05-1.05), male (aHR, 0.81; 95% CI, 0.79-0.84), and Black vs White (aHR, 1.16; 95% CI, 1.11-1.21), and among those who received systemic corticosteroids in the 3 months before diagnosis (aHR, 1.10; 95% CI, 1.06-1.14), were hospitalized in the year before diagnosis (aHR, 1.35; 95% CI, 1.30-1.41), and had a history of smoking (aHR, 1.20; 95% CI, 1.16-1.24) and drug abuse (aHR, 1.34; 95% CI, 1.25-1.43).
 

Unexpected Results

“One surprising finding was that the incidence of MACE in patients with moderate to severe AD was actually lower than that in non-AD matched controls and significantly lower compared to patients with moderate to severe RA,” Dr. Bunick said. “This contrasts with the expectation that increased systemic inflammation in moderate to severe AD would correspond with a higher incidence of MACE.”

Another unexpected result, he said, was that, among patients with moderate to severe AD, the risk for MACE was not significantly different from that of non-AD matched controls, suggesting that the inflammatory burden in AD might not translate to as high a cardiovascular risk as previously assumed.

Dr. Bunick noted that advanced treatments for AD such as Janus kinase (JAK) inhibitors (upadacitinib and abrocitinib) have a class boxed warning for MACE based on a study of another JAK inhibitor (tofacitinib) in patients with RA, but “this may not apply to AD because patients with AD have a lower risk for MACE.”

In his opinion, he said, the study “underscores the importance of understanding the specific risks associated with different inflammatory conditions.” Moreover, “it emphasizes the potential benefits of newer systemic therapies in potentially mitigating cardiovascular risks in patients with moderate to severe AD.”

Dr. Bunick acknowledged certain limitations of the study, including its retrospective design and reliance on administrative claims data, which “may introduce coding errors and misclassification,” and the generalizability of the results, which may be limited to the US population.

AbbVie funded the study, and three of the coauthors are employees of the company. Dr. Bunick disclosed that he has served as an investigator and/or a consultant for AbbVie, Almirall, Apogee, Arcutis Biotherapeutics, Connect Biopharma, Daiichi Sankyo, EPI Health/Novan, LEO, Lilly, Novartis, Ortho Dermatologics, Palvella Therapeutics, Pfizer, Sanofi Regeneron, Sun, Takeda, Timber, and UCB.

A version of this article appeared on Medscape.com.

Patients with atopic dermatitis (AD) had a lower risk for major adverse cardiovascular events (MACE) than the general population, and this risk was significantly lower than that of patients with rheumatoid arthritis (RA), according to an analysis of national claims data.

The results of the analysis were presented during a poster session at the Revolutionizing Atopic Dermatitis conference in Chicago. “While it is known that atopic dermatitis is associated with some comorbidities, the specific risk of major adverse cardiovascular events in patients with AD, especially those with moderate to severe AD within the US population, is unclear,” the study’s first author Christopher G. Bunick, MD, PhD, said in an interview following the conference.

To characterize the risk for MACE in patients with AD vs matched controls without AD (non-AD) and patients with RA, Dr. Bunick, associate professor of dermatology at Yale University, New Haven, Connecticut, and colleagues retrospectively evaluated US claims data from Optum’s Clinformatics Data Mart. The study population consisted of 381,221 patients aged 18 years and older who were diagnosed with AD from March 2017 to March 2023. Comparator groups included 381,221 non-AD controls matched by age, sex, and cohort entry, and 97,445 patients diagnosed with RA based on at least two claims for RA ≥ 7 days apart.

Patients were classified as having moderate to severe disease if they received dupilumab for AD or advanced systemic therapy for RA at any time during the follow-up period. The matched moderate to severe AD and non-AD cohorts were composed of 7134 patients each. The incidence of MACE was defined as inpatient hospitalization with myocardial infarction or stroke. The researchers used multivariable Cox proportional hazard models adjusted for baseline demographics, comorbidities, and medications to calculate the relative risk for MACE.
 

MACE Incidence, Relative Risk

The mean age of the AD cohort and non-AD matched controls was 58 years, and the mean age of the RA cohort was 67 years. The incidence of MACE per 100 patient-years was 1.78 among patients with AD, 1.83 among non-AD matched controls, and 2.12 among patients with RA. Patients with moderate to severe AD had a MACE incidence of 1.18 per 100 patient-years, which was lower than that of non-AD matched controls (1.52) and patients with moderate to severe RA (1.67).

In other findings, the relative risk for MACE in patients with AD was lower vs non-AD controls (adjusted hazard ratio [aHR], 0.91; 95% CI, 0.89-0.93; P < .001) and patients with RA (aHR, 0.83; 95% CI, 0.80-0.85; P < .001). Among patients with moderate to severe AD, MACE risk was similar to that of non-AD matched controls (aHR, 0.92; 95% CI, 0.73-1.14) and lower vs those with moderate to severe RA (aHR, 0.83; 95% CI, 0.73-0.94; P < .01).

MACE risk associated with AD was greater in patients who were older (per year, aHR, 1.05; 95% CI, 1.05-1.05), male (aHR, 0.81; 95% CI, 0.79-0.84), and Black vs White (aHR, 1.16; 95% CI, 1.11-1.21), and among those who received systemic corticosteroids in the 3 months before diagnosis (aHR, 1.10; 95% CI, 1.06-1.14), were hospitalized in the year before diagnosis (aHR, 1.35; 95% CI, 1.30-1.41), and had a history of smoking (aHR, 1.20; 95% CI, 1.16-1.24) and drug abuse (aHR, 1.34; 95% CI, 1.25-1.43).
 

Unexpected Results

“One surprising finding was that the incidence of MACE in patients with moderate to severe AD was actually lower than that in non-AD matched controls and significantly lower compared to patients with moderate to severe RA,” Dr. Bunick said. “This contrasts with the expectation that increased systemic inflammation in moderate to severe AD would correspond with a higher incidence of MACE.”

Another unexpected result, he said, was that, among patients with moderate to severe AD, the risk for MACE was not significantly different from that of non-AD matched controls, suggesting that the inflammatory burden in AD might not translate to as high a cardiovascular risk as previously assumed.

Dr. Bunick noted that advanced treatments for AD such as Janus kinase (JAK) inhibitors (upadacitinib and abrocitinib) have a class boxed warning for MACE based on a study of another JAK inhibitor (tofacitinib) in patients with RA, but “this may not apply to AD because patients with AD have a lower risk for MACE.”

In his opinion, he said, the study “underscores the importance of understanding the specific risks associated with different inflammatory conditions.” Moreover, “it emphasizes the potential benefits of newer systemic therapies in potentially mitigating cardiovascular risks in patients with moderate to severe AD.”

Dr. Bunick acknowledged certain limitations of the study, including its retrospective design and reliance on administrative claims data, which “may introduce coding errors and misclassification,” and the generalizability of the results, which may be limited to the US population.

AbbVie funded the study, and three of the coauthors are employees of the company. Dr. Bunick disclosed that he has served as an investigator and/or a consultant for AbbVie, Almirall, Apogee, Arcutis Biotherapeutics, Connect Biopharma, Daiichi Sankyo, EPI Health/Novan, LEO, Lilly, Novartis, Ortho Dermatologics, Palvella Therapeutics, Pfizer, Sanofi Regeneron, Sun, Takeda, Timber, and UCB.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Hi. I’m Dr Eileen Hsich. I’m the medical director for heart transplantation at the Cleveland Clinic, and my specialty is sex differences in heart failure. I’m excited to talk to you about heart failure treatment in women, addressing the differences in managing heart failure in women as well as practical tips for clinicians. You think that I’m going to be starting off by telling you about the differences in how we’re going to manage the patients, but I’m not. The reason I’m not going to do that is because our national guidelines are not sex specific.

What I’m really going to discuss with you today are the data so that you can decide for yourself what we should do and whether there really are differences. As we begin, I always think about the prevalence of the disease. Currently, there are 6.7 million Americans with heart failure, and approximately 45% of them are women. Globally, our best research shows that there are over 56 million people living with heart failure, and half of them are women.

We also know that there are different underlying causes in women and men. For women, the four risk factors are hypertension, diabetes, atrial fibrillation (AFib), and left bundle branch block. I know you knew about hypertension. Diabetes may not have been right up there in your mind. You see many women with AFib, so I know that you were thinking about it. We’re going to come back to left bundle branch block; it really is very interesting.

For men, it is the risk for heart failure development after a myocardial infarction. Men are more likely to have an ischemic cardiomyopathy. It is also important to state that when women have heart failure, it is often with more preserved ejection fraction. We know that heart failure with preserved ejection fraction (HFpEF) is more common in women and heart failure with reduced ejection fraction (HFrEF) is more common in men.

Now we’re going to talk about the four pillars in medical management, and we’re going to start out with the easy medications that show no sex differences in benefit. The mineralocorticoid receptor antagonists (MRAs) show that there are no sex differences in regard to benefit. Women benefit as much as men, based on two of the largest studies, which were the RALES study, which studied heart failure that was ischemic and nonischemic, and then the EPHESUS study, which was specific to patients who had myocardial infarction. There was a mortality benefit in the women.

The next set of drugs that we’re going to mention are the sodium-glucose cotransporter 2 (SGLT2) inhibitors. The combined endpoint for women and men was a combined endpoint of death and heart failure hospitalization. No matter what the ejection fraction was, women benefited like men for this drug.

The third class of agents that I want to discuss is the beta-blockers, which are really very interesting because they’re so powerful. The studies for these drugs were stopped prematurely. When you take into consideration that women are underenrolled in clinical trials, remember that the studies for these drugs were stopped, so there weren’t that many women. The fact that we showed a mortality benefit is really important.

The first drug that we’re going to refer to is bisoprolol because CIBIS II was the first trial for this drug to demonstrate a mortality benefit in women and men. The second drug that I want to mention is metoprolol XL, which did not demonstrate a mortality benefit in the MERIT-HF study, but did demonstrate a benefit in reduced heart failure hospitalizations, which is also very important.

The third drug is carvedilol, which had been shown to reduce a combined endpoint of mortality and heart failure hospitalizations for patients with moderate symptoms. When I talk about these studies, they have anywhere from 250 to 1000 women enrolled, so these are relatively small studies and they still did demonstrate a benefit.

When we talk about angiotensin receptor–neprilysin inhibitors (ARNI), I think that’s when it gets a little complex. The data are not very clear because ARNI is a combination pill — sacubitril combined with valsartan. When you have an ideal control for a study and you want to know what your magic ingredient is, which is the sacubitril, you really want to compare valsartan with ARNI so that you can find out what your magic little ingredient is doing.

When we had the PARAGON-HF study, which was for HFpEF patients who had an ejection fraction greater than 45%, there was a benefit in the women and not in the men, and that really was in the women with the lower ejection fractions. That’s very interesting because the control was valsartan.

When we had the PARADIGM-HF study, that was more complex. The control was an angiotensin-converting enzyme (ACE) inhibitor, which is not an ideal control for women since, even in a meta-analysis that had over 1000 women, there has not been a proven benefit. The confidence intervals remain wide. Therefore, it’s not quite a fair comparison to randomize women to ARNI versus an ACE inhibitor. Comparing ARNI to valsartan would be better in order to determine the additional benefit of sacubitril since valsartan alone has already been shown, in the Val-HeFT study, to reduce heart failure hospitalizations in women — although not mortality. There was a benefit.

When you look at the PARADIGM-HF study, which was for HFrEF patients, and you see that there is a benefit in the women, where the combined endpoint was heart failure hospitalization and mortality, you then see that there’s a figure that shows what happens when we look at mortality alone. The benefit is not driven by mortality; it’s driven by heart failure hospitalizations for the women, for which valsartan already had been shown to do this. Therefore, I don’t know if sacubitril/valsartan is more powerful because we didn’t have the right control in studies. From my standpoint, the data really are not there. We can all have our own biased opinions.

When we talk about devices, that gets really interesting because it goes back to those risk factors. We’re going to start with implantable cardioverter defibrillators (ICDs). We have shown in many ICD trials that women and men had similar survival. There were very few women in these device trials. If you think the medical trials had only a few women, just imagine what the ICD trials had.

Santangeli and colleagues hypothesized that an ICD only saves you from sudden death. It doesn›t really save you from anything else. In heart failure, women do live longer than men. Is this device really saving you? They weren’t interested in all-cause mortality; they were interested in whether the device fired appropriately for ventricular tachycardia or ventricular fibrillation. They demonstrated in that meta-analysis that it was not very clear that women had the benefit. The rationale behind that comes from the MADIT studies that showed that men were more likely than women to have ventricular arrhythmias.

This is also true based on the Seattle Heart Failure Model. The derivation cohort had very few ICDs at that time, and women were less likely than men to have ventricular arrhythmias as the cause of death. It’s not that we shouldn’t put them in — I very strongly believe that we should — but we don’t have that data.

In fact, in the Santangeli and colleagues study, women were more likely to have inappropriate firing for AFib. Remember that we talked about how one of the risk factors for heart failure was AFib. Women are more likely to have AFib and the ICD firing for AFib and not ventricular arrhythmias. This may be dependent on the type of cardiomyopathy.

Next, we’re going to talk about biventricular pacemakers. Women tend to benefit more so that there is an improvement in symptoms and survival. What is fascinating is that left bundle branch block is a risk factor for the development of heart failure in women, which makes this next statement even more fascinating.

The FDA does their own analysis when they are reviewing devices and everything else, and they published one of them in JAMA Internal Medicine, taking three studies and seeing the benefit in women and men. They found that everybody benefits when the left bundle branch block has a QRS greater than 150 milliseconds. But with a QRS between 130 and 149 milliseconds, only the women benefited. That›s fascinating because that is a risk factor — the development of the left bundle branch block causing heart failure in women. It makes you wonder whether you are correcting something that actually was responsible for their heart failure.

In advanced heart failure, we have left ventricular assist devices (LVADs) and heart transplantation. For years, we couldn’t get LVADs small enough to fit in women. When they were larger, there were complications that were more common in women, such as stroke. With the newer devices — the HeartMate 3 is small, for instance — complications for everyone are very infrequent, and women and men benefit. I’m going to encourage clinicians to use them.

For heart transplantation, as I mentioned before, women tend to get HFpEF. I didn’t mention that they get heart failure when they’re older, for the most part. There are fewer women who are transplanted than men and eligible at younger ages. What we had for decades was that women were dying while they were on the waitlist for heart transplantation at a faster rate than men but living longer after transplantation. As LVADs became more appropriately sized for women, the complication rates went down; and we did see an improvement on the waitlist mortality rate before we changed the allocation system. But it really wasn’t until after we changed the allocation system in 2018 that we saw great success. Now, women have similar survival while on the waitlist. They’re transplanted at a faster rate despite the fact that they’re less likely to receive the temporary mechanical support, and they tend to still do very well.

I’ll leave you with the thought that women and men are different. We have different underlying diseases, different onset for the development of heart failure, and different ejection fractions in instances when heart failure develops. We have some differences in therapy response. Thank you.

Dr. Hsich disclosed ties with Natera, DEFINE steering committee (no money), and MEDCAC (Medicare/Medicaid) committee. She received research grant from the National Institutes of Health.
 

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Hi. I’m Dr Eileen Hsich. I’m the medical director for heart transplantation at the Cleveland Clinic, and my specialty is sex differences in heart failure. I’m excited to talk to you about heart failure treatment in women, addressing the differences in managing heart failure in women as well as practical tips for clinicians. You think that I’m going to be starting off by telling you about the differences in how we’re going to manage the patients, but I’m not. The reason I’m not going to do that is because our national guidelines are not sex specific.

What I’m really going to discuss with you today are the data so that you can decide for yourself what we should do and whether there really are differences. As we begin, I always think about the prevalence of the disease. Currently, there are 6.7 million Americans with heart failure, and approximately 45% of them are women. Globally, our best research shows that there are over 56 million people living with heart failure, and half of them are women.

We also know that there are different underlying causes in women and men. For women, the four risk factors are hypertension, diabetes, atrial fibrillation (AFib), and left bundle branch block. I know you knew about hypertension. Diabetes may not have been right up there in your mind. You see many women with AFib, so I know that you were thinking about it. We’re going to come back to left bundle branch block; it really is very interesting.

For men, it is the risk for heart failure development after a myocardial infarction. Men are more likely to have an ischemic cardiomyopathy. It is also important to state that when women have heart failure, it is often with more preserved ejection fraction. We know that heart failure with preserved ejection fraction (HFpEF) is more common in women and heart failure with reduced ejection fraction (HFrEF) is more common in men.

Now we’re going to talk about the four pillars in medical management, and we’re going to start out with the easy medications that show no sex differences in benefit. The mineralocorticoid receptor antagonists (MRAs) show that there are no sex differences in regard to benefit. Women benefit as much as men, based on two of the largest studies, which were the RALES study, which studied heart failure that was ischemic and nonischemic, and then the EPHESUS study, which was specific to patients who had myocardial infarction. There was a mortality benefit in the women.

The next set of drugs that we’re going to mention are the sodium-glucose cotransporter 2 (SGLT2) inhibitors. The combined endpoint for women and men was a combined endpoint of death and heart failure hospitalization. No matter what the ejection fraction was, women benefited like men for this drug.

The third class of agents that I want to discuss is the beta-blockers, which are really very interesting because they’re so powerful. The studies for these drugs were stopped prematurely. When you take into consideration that women are underenrolled in clinical trials, remember that the studies for these drugs were stopped, so there weren’t that many women. The fact that we showed a mortality benefit is really important.

The first drug that we’re going to refer to is bisoprolol because CIBIS II was the first trial for this drug to demonstrate a mortality benefit in women and men. The second drug that I want to mention is metoprolol XL, which did not demonstrate a mortality benefit in the MERIT-HF study, but did demonstrate a benefit in reduced heart failure hospitalizations, which is also very important.

The third drug is carvedilol, which had been shown to reduce a combined endpoint of mortality and heart failure hospitalizations for patients with moderate symptoms. When I talk about these studies, they have anywhere from 250 to 1000 women enrolled, so these are relatively small studies and they still did demonstrate a benefit.

When we talk about angiotensin receptor–neprilysin inhibitors (ARNI), I think that’s when it gets a little complex. The data are not very clear because ARNI is a combination pill — sacubitril combined with valsartan. When you have an ideal control for a study and you want to know what your magic ingredient is, which is the sacubitril, you really want to compare valsartan with ARNI so that you can find out what your magic little ingredient is doing.

When we had the PARAGON-HF study, which was for HFpEF patients who had an ejection fraction greater than 45%, there was a benefit in the women and not in the men, and that really was in the women with the lower ejection fractions. That’s very interesting because the control was valsartan.

When we had the PARADIGM-HF study, that was more complex. The control was an angiotensin-converting enzyme (ACE) inhibitor, which is not an ideal control for women since, even in a meta-analysis that had over 1000 women, there has not been a proven benefit. The confidence intervals remain wide. Therefore, it’s not quite a fair comparison to randomize women to ARNI versus an ACE inhibitor. Comparing ARNI to valsartan would be better in order to determine the additional benefit of sacubitril since valsartan alone has already been shown, in the Val-HeFT study, to reduce heart failure hospitalizations in women — although not mortality. There was a benefit.

When you look at the PARADIGM-HF study, which was for HFrEF patients, and you see that there is a benefit in the women, where the combined endpoint was heart failure hospitalization and mortality, you then see that there’s a figure that shows what happens when we look at mortality alone. The benefit is not driven by mortality; it’s driven by heart failure hospitalizations for the women, for which valsartan already had been shown to do this. Therefore, I don’t know if sacubitril/valsartan is more powerful because we didn’t have the right control in studies. From my standpoint, the data really are not there. We can all have our own biased opinions.

When we talk about devices, that gets really interesting because it goes back to those risk factors. We’re going to start with implantable cardioverter defibrillators (ICDs). We have shown in many ICD trials that women and men had similar survival. There were very few women in these device trials. If you think the medical trials had only a few women, just imagine what the ICD trials had.

Santangeli and colleagues hypothesized that an ICD only saves you from sudden death. It doesn›t really save you from anything else. In heart failure, women do live longer than men. Is this device really saving you? They weren’t interested in all-cause mortality; they were interested in whether the device fired appropriately for ventricular tachycardia or ventricular fibrillation. They demonstrated in that meta-analysis that it was not very clear that women had the benefit. The rationale behind that comes from the MADIT studies that showed that men were more likely than women to have ventricular arrhythmias.

This is also true based on the Seattle Heart Failure Model. The derivation cohort had very few ICDs at that time, and women were less likely than men to have ventricular arrhythmias as the cause of death. It’s not that we shouldn’t put them in — I very strongly believe that we should — but we don’t have that data.

In fact, in the Santangeli and colleagues study, women were more likely to have inappropriate firing for AFib. Remember that we talked about how one of the risk factors for heart failure was AFib. Women are more likely to have AFib and the ICD firing for AFib and not ventricular arrhythmias. This may be dependent on the type of cardiomyopathy.

Next, we’re going to talk about biventricular pacemakers. Women tend to benefit more so that there is an improvement in symptoms and survival. What is fascinating is that left bundle branch block is a risk factor for the development of heart failure in women, which makes this next statement even more fascinating.

The FDA does their own analysis when they are reviewing devices and everything else, and they published one of them in JAMA Internal Medicine, taking three studies and seeing the benefit in women and men. They found that everybody benefits when the left bundle branch block has a QRS greater than 150 milliseconds. But with a QRS between 130 and 149 milliseconds, only the women benefited. That›s fascinating because that is a risk factor — the development of the left bundle branch block causing heart failure in women. It makes you wonder whether you are correcting something that actually was responsible for their heart failure.

In advanced heart failure, we have left ventricular assist devices (LVADs) and heart transplantation. For years, we couldn’t get LVADs small enough to fit in women. When they were larger, there were complications that were more common in women, such as stroke. With the newer devices — the HeartMate 3 is small, for instance — complications for everyone are very infrequent, and women and men benefit. I’m going to encourage clinicians to use them.

For heart transplantation, as I mentioned before, women tend to get HFpEF. I didn’t mention that they get heart failure when they’re older, for the most part. There are fewer women who are transplanted than men and eligible at younger ages. What we had for decades was that women were dying while they were on the waitlist for heart transplantation at a faster rate than men but living longer after transplantation. As LVADs became more appropriately sized for women, the complication rates went down; and we did see an improvement on the waitlist mortality rate before we changed the allocation system. But it really wasn’t until after we changed the allocation system in 2018 that we saw great success. Now, women have similar survival while on the waitlist. They’re transplanted at a faster rate despite the fact that they’re less likely to receive the temporary mechanical support, and they tend to still do very well.

I’ll leave you with the thought that women and men are different. We have different underlying diseases, different onset for the development of heart failure, and different ejection fractions in instances when heart failure develops. We have some differences in therapy response. Thank you.

Dr. Hsich disclosed ties with Natera, DEFINE steering committee (no money), and MEDCAC (Medicare/Medicaid) committee. She received research grant from the National Institutes of Health.
 

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Hi. I’m Dr Eileen Hsich. I’m the medical director for heart transplantation at the Cleveland Clinic, and my specialty is sex differences in heart failure. I’m excited to talk to you about heart failure treatment in women, addressing the differences in managing heart failure in women as well as practical tips for clinicians. You think that I’m going to be starting off by telling you about the differences in how we’re going to manage the patients, but I’m not. The reason I’m not going to do that is because our national guidelines are not sex specific.

What I’m really going to discuss with you today are the data so that you can decide for yourself what we should do and whether there really are differences. As we begin, I always think about the prevalence of the disease. Currently, there are 6.7 million Americans with heart failure, and approximately 45% of them are women. Globally, our best research shows that there are over 56 million people living with heart failure, and half of them are women.

We also know that there are different underlying causes in women and men. For women, the four risk factors are hypertension, diabetes, atrial fibrillation (AFib), and left bundle branch block. I know you knew about hypertension. Diabetes may not have been right up there in your mind. You see many women with AFib, so I know that you were thinking about it. We’re going to come back to left bundle branch block; it really is very interesting.

For men, it is the risk for heart failure development after a myocardial infarction. Men are more likely to have an ischemic cardiomyopathy. It is also important to state that when women have heart failure, it is often with more preserved ejection fraction. We know that heart failure with preserved ejection fraction (HFpEF) is more common in women and heart failure with reduced ejection fraction (HFrEF) is more common in men.

Now we’re going to talk about the four pillars in medical management, and we’re going to start out with the easy medications that show no sex differences in benefit. The mineralocorticoid receptor antagonists (MRAs) show that there are no sex differences in regard to benefit. Women benefit as much as men, based on two of the largest studies, which were the RALES study, which studied heart failure that was ischemic and nonischemic, and then the EPHESUS study, which was specific to patients who had myocardial infarction. There was a mortality benefit in the women.

The next set of drugs that we’re going to mention are the sodium-glucose cotransporter 2 (SGLT2) inhibitors. The combined endpoint for women and men was a combined endpoint of death and heart failure hospitalization. No matter what the ejection fraction was, women benefited like men for this drug.

The third class of agents that I want to discuss is the beta-blockers, which are really very interesting because they’re so powerful. The studies for these drugs were stopped prematurely. When you take into consideration that women are underenrolled in clinical trials, remember that the studies for these drugs were stopped, so there weren’t that many women. The fact that we showed a mortality benefit is really important.

The first drug that we’re going to refer to is bisoprolol because CIBIS II was the first trial for this drug to demonstrate a mortality benefit in women and men. The second drug that I want to mention is metoprolol XL, which did not demonstrate a mortality benefit in the MERIT-HF study, but did demonstrate a benefit in reduced heart failure hospitalizations, which is also very important.

The third drug is carvedilol, which had been shown to reduce a combined endpoint of mortality and heart failure hospitalizations for patients with moderate symptoms. When I talk about these studies, they have anywhere from 250 to 1000 women enrolled, so these are relatively small studies and they still did demonstrate a benefit.

When we talk about angiotensin receptor–neprilysin inhibitors (ARNI), I think that’s when it gets a little complex. The data are not very clear because ARNI is a combination pill — sacubitril combined with valsartan. When you have an ideal control for a study and you want to know what your magic ingredient is, which is the sacubitril, you really want to compare valsartan with ARNI so that you can find out what your magic little ingredient is doing.

When we had the PARAGON-HF study, which was for HFpEF patients who had an ejection fraction greater than 45%, there was a benefit in the women and not in the men, and that really was in the women with the lower ejection fractions. That’s very interesting because the control was valsartan.

When we had the PARADIGM-HF study, that was more complex. The control was an angiotensin-converting enzyme (ACE) inhibitor, which is not an ideal control for women since, even in a meta-analysis that had over 1000 women, there has not been a proven benefit. The confidence intervals remain wide. Therefore, it’s not quite a fair comparison to randomize women to ARNI versus an ACE inhibitor. Comparing ARNI to valsartan would be better in order to determine the additional benefit of sacubitril since valsartan alone has already been shown, in the Val-HeFT study, to reduce heart failure hospitalizations in women — although not mortality. There was a benefit.

When you look at the PARADIGM-HF study, which was for HFrEF patients, and you see that there is a benefit in the women, where the combined endpoint was heart failure hospitalization and mortality, you then see that there’s a figure that shows what happens when we look at mortality alone. The benefit is not driven by mortality; it’s driven by heart failure hospitalizations for the women, for which valsartan already had been shown to do this. Therefore, I don’t know if sacubitril/valsartan is more powerful because we didn’t have the right control in studies. From my standpoint, the data really are not there. We can all have our own biased opinions.

When we talk about devices, that gets really interesting because it goes back to those risk factors. We’re going to start with implantable cardioverter defibrillators (ICDs). We have shown in many ICD trials that women and men had similar survival. There were very few women in these device trials. If you think the medical trials had only a few women, just imagine what the ICD trials had.

Santangeli and colleagues hypothesized that an ICD only saves you from sudden death. It doesn›t really save you from anything else. In heart failure, women do live longer than men. Is this device really saving you? They weren’t interested in all-cause mortality; they were interested in whether the device fired appropriately for ventricular tachycardia or ventricular fibrillation. They demonstrated in that meta-analysis that it was not very clear that women had the benefit. The rationale behind that comes from the MADIT studies that showed that men were more likely than women to have ventricular arrhythmias.

This is also true based on the Seattle Heart Failure Model. The derivation cohort had very few ICDs at that time, and women were less likely than men to have ventricular arrhythmias as the cause of death. It’s not that we shouldn’t put them in — I very strongly believe that we should — but we don’t have that data.

In fact, in the Santangeli and colleagues study, women were more likely to have inappropriate firing for AFib. Remember that we talked about how one of the risk factors for heart failure was AFib. Women are more likely to have AFib and the ICD firing for AFib and not ventricular arrhythmias. This may be dependent on the type of cardiomyopathy.

Next, we’re going to talk about biventricular pacemakers. Women tend to benefit more so that there is an improvement in symptoms and survival. What is fascinating is that left bundle branch block is a risk factor for the development of heart failure in women, which makes this next statement even more fascinating.

The FDA does their own analysis when they are reviewing devices and everything else, and they published one of them in JAMA Internal Medicine, taking three studies and seeing the benefit in women and men. They found that everybody benefits when the left bundle branch block has a QRS greater than 150 milliseconds. But with a QRS between 130 and 149 milliseconds, only the women benefited. That›s fascinating because that is a risk factor — the development of the left bundle branch block causing heart failure in women. It makes you wonder whether you are correcting something that actually was responsible for their heart failure.

In advanced heart failure, we have left ventricular assist devices (LVADs) and heart transplantation. For years, we couldn’t get LVADs small enough to fit in women. When they were larger, there were complications that were more common in women, such as stroke. With the newer devices — the HeartMate 3 is small, for instance — complications for everyone are very infrequent, and women and men benefit. I’m going to encourage clinicians to use them.

For heart transplantation, as I mentioned before, women tend to get HFpEF. I didn’t mention that they get heart failure when they’re older, for the most part. There are fewer women who are transplanted than men and eligible at younger ages. What we had for decades was that women were dying while they were on the waitlist for heart transplantation at a faster rate than men but living longer after transplantation. As LVADs became more appropriately sized for women, the complication rates went down; and we did see an improvement on the waitlist mortality rate before we changed the allocation system. But it really wasn’t until after we changed the allocation system in 2018 that we saw great success. Now, women have similar survival while on the waitlist. They’re transplanted at a faster rate despite the fact that they’re less likely to receive the temporary mechanical support, and they tend to still do very well.

I’ll leave you with the thought that women and men are different. We have different underlying diseases, different onset for the development of heart failure, and different ejection fractions in instances when heart failure develops. We have some differences in therapy response. Thank you.

Dr. Hsich disclosed ties with Natera, DEFINE steering committee (no money), and MEDCAC (Medicare/Medicaid) committee. She received research grant from the National Institutes of Health.
 

A version of this article appeared on Medscape.com.

BOSTON — A Mediterranean diet with extra virgin olive oil (EVOO) significantly reduced the risk for tachyarrhythmia recurrence after atrial fibrillation (AF) ablation in patients with paroxysmal disease, but the diet had less of an impact on patients with persistent AF, a new study showed.

“An intervention with the Mediterranean diet with EVOO produced a nonsignificant reduction in any atrial tachycardia in a selected population after undergoing atrial fibrillation ablation, but this intervention produced a significant reduction in any atrial tachyarrhythmias in patients with paroxysmal AF,” said Maria Teresa Barrio-Lopez, MD, PhD, an electrophysiologist at University Hospital HM Monteprincipe in Madrid, Spain, who presented results from the PREDIMAR trial at the Heart Rhythm Society (HRS) 2024 annual meeting.

The PREDIMAR study enrolled 720 patients from the larger PREDIMED study, which showed that patients without AF at enrollment and who followed a Mediterranean diet enriched with EVOO had a 38% lower rate of incidental AF than control individuals.

PREDIMAR evaluated the impact of the diet on arrhythmia recurrence in patients after ablation. The patients were randomized in a 1:1 ratio to either the dietary intervention group or the control group.
 

PREDIMAR Study Results

The overall difference in the rate of AF recurrence in the 3-18 months after ablation between the dietary intervention and control groups was nonsignificant (34.8% vs 37.5%).

However, among the 431 patients with paroxysmal AF, 25.2% in the diet group and 34.7% in the control group had no tachyarrhythmia recurrence, which translates into a 31% lower risk in the diet group.

In this study, the diet was rich in fish, nuts, fruits, and vegetables and was complemented with EVOO. Participants were also permitted moderate wine consumption.

The intervention involved dietitians who remotely followed patients and made periodic telephone calls to encourage them to stay on the diet. Participants had weight and body measurements taken at baseline and at 3, 6, 12, and 18 months and underwent an ECG at 6, 12, and 18 months. Labs were obtained at baseline and at 12 months. Participants were also given educational materials throughout the intervention.

Average scores, based on a scale of 0-13, excluding an item for wine intake, were 7.8 in the diet group and 7.2 in the control group.

Daily average alcohol intake was higher in the diet group than in the control group (9.8 vs 8.2 g), but “the weight of the patient during the study didn’t change in any group,” Dr. Barrio-Lopez reported.

Baseline characteristics were similar in the two groups. About 60% were taking antiarrhythmic drugs, and about 84% were taking anticoagulants.
 

‘A Tour de Force’

PREDIMAR was “really a tour de force,” Christine Albert, MD, MPH, chair of cardiology at the Smidt Heart Institute at the Cedars-Sinai Medical Center in Los Angeles, California, said during a commentary presented at HRS. “We talk about how we’re going to do these dietary interventions and weight loss and all the risk-factor reduction, and they pulled it off with 700 individuals and also did it in a way that was very novel.”

This is the first large-scale dietary intervention trial of patients with AF. However, Dr. Albert noted later in an interview, the Mediterranean diet poses potential challenges for some people with AF.

“The Mediterranean diet recommends that people drink wine, but then there’s clear evidence that abstinence from alcohol actually reduces recurrences of atrial fibrillation, so even though there are a lot of things about the Mediterranean diet that are probably healthy and good for atrial fibrillation, that aspect of it might be working against the patient,” she explained.

The finding that patients in the Mediterranean diet group experienced no significant weight loss could be counterintuitive when it comes to preventing AF. But “you could adapt the diet for AF,” Dr. Albert said. You could “leave out the wine and focus more on weight loss if the patient is obese because those are also the pillars of what we’ve learned for patients with atrial fibrillation.”

Making weight loss a key component of the study could be significant for the American population. “At least in the United States, that’s a huge part of the risk factors for atrial fibrillation after ablation,” she said.

The remote follow-up component of the PREDIMAR study is also intriguing. “I think what’s most exciting about what they did is, they showed they can do all these things remotely,” Dr. Albert added.

Dr. Barrio-Lopez had no relevant financial relationships. Dr. Albert disclosed relationships with Abbott, Roche Diagnostics, St. Jude Medical, Boston Scientific, Medtronic, and Element Science.

A version of this article appeared on Medscape.com.

BOSTON — A Mediterranean diet with extra virgin olive oil (EVOO) significantly reduced the risk for tachyarrhythmia recurrence after atrial fibrillation (AF) ablation in patients with paroxysmal disease, but the diet had less of an impact on patients with persistent AF, a new study showed.

“An intervention with the Mediterranean diet with EVOO produced a nonsignificant reduction in any atrial tachycardia in a selected population after undergoing atrial fibrillation ablation, but this intervention produced a significant reduction in any atrial tachyarrhythmias in patients with paroxysmal AF,” said Maria Teresa Barrio-Lopez, MD, PhD, an electrophysiologist at University Hospital HM Monteprincipe in Madrid, Spain, who presented results from the PREDIMAR trial at the Heart Rhythm Society (HRS) 2024 annual meeting.

The PREDIMAR study enrolled 720 patients from the larger PREDIMED study, which showed that patients without AF at enrollment and who followed a Mediterranean diet enriched with EVOO had a 38% lower rate of incidental AF than control individuals.

PREDIMAR evaluated the impact of the diet on arrhythmia recurrence in patients after ablation. The patients were randomized in a 1:1 ratio to either the dietary intervention group or the control group.
 

PREDIMAR Study Results

The overall difference in the rate of AF recurrence in the 3-18 months after ablation between the dietary intervention and control groups was nonsignificant (34.8% vs 37.5%).

However, among the 431 patients with paroxysmal AF, 25.2% in the diet group and 34.7% in the control group had no tachyarrhythmia recurrence, which translates into a 31% lower risk in the diet group.

In this study, the diet was rich in fish, nuts, fruits, and vegetables and was complemented with EVOO. Participants were also permitted moderate wine consumption.

The intervention involved dietitians who remotely followed patients and made periodic telephone calls to encourage them to stay on the diet. Participants had weight and body measurements taken at baseline and at 3, 6, 12, and 18 months and underwent an ECG at 6, 12, and 18 months. Labs were obtained at baseline and at 12 months. Participants were also given educational materials throughout the intervention.

Average scores, based on a scale of 0-13, excluding an item for wine intake, were 7.8 in the diet group and 7.2 in the control group.

Daily average alcohol intake was higher in the diet group than in the control group (9.8 vs 8.2 g), but “the weight of the patient during the study didn’t change in any group,” Dr. Barrio-Lopez reported.

Baseline characteristics were similar in the two groups. About 60% were taking antiarrhythmic drugs, and about 84% were taking anticoagulants.
 

‘A Tour de Force’

PREDIMAR was “really a tour de force,” Christine Albert, MD, MPH, chair of cardiology at the Smidt Heart Institute at the Cedars-Sinai Medical Center in Los Angeles, California, said during a commentary presented at HRS. “We talk about how we’re going to do these dietary interventions and weight loss and all the risk-factor reduction, and they pulled it off with 700 individuals and also did it in a way that was very novel.”

This is the first large-scale dietary intervention trial of patients with AF. However, Dr. Albert noted later in an interview, the Mediterranean diet poses potential challenges for some people with AF.

“The Mediterranean diet recommends that people drink wine, but then there’s clear evidence that abstinence from alcohol actually reduces recurrences of atrial fibrillation, so even though there are a lot of things about the Mediterranean diet that are probably healthy and good for atrial fibrillation, that aspect of it might be working against the patient,” she explained.

The finding that patients in the Mediterranean diet group experienced no significant weight loss could be counterintuitive when it comes to preventing AF. But “you could adapt the diet for AF,” Dr. Albert said. You could “leave out the wine and focus more on weight loss if the patient is obese because those are also the pillars of what we’ve learned for patients with atrial fibrillation.”

Making weight loss a key component of the study could be significant for the American population. “At least in the United States, that’s a huge part of the risk factors for atrial fibrillation after ablation,” she said.

The remote follow-up component of the PREDIMAR study is also intriguing. “I think what’s most exciting about what they did is, they showed they can do all these things remotely,” Dr. Albert added.

Dr. Barrio-Lopez had no relevant financial relationships. Dr. Albert disclosed relationships with Abbott, Roche Diagnostics, St. Jude Medical, Boston Scientific, Medtronic, and Element Science.

A version of this article appeared on Medscape.com.

BOSTON — A Mediterranean diet with extra virgin olive oil (EVOO) significantly reduced the risk for tachyarrhythmia recurrence after atrial fibrillation (AF) ablation in patients with paroxysmal disease, but the diet had less of an impact on patients with persistent AF, a new study showed.

“An intervention with the Mediterranean diet with EVOO produced a nonsignificant reduction in any atrial tachycardia in a selected population after undergoing atrial fibrillation ablation, but this intervention produced a significant reduction in any atrial tachyarrhythmias in patients with paroxysmal AF,” said Maria Teresa Barrio-Lopez, MD, PhD, an electrophysiologist at University Hospital HM Monteprincipe in Madrid, Spain, who presented results from the PREDIMAR trial at the Heart Rhythm Society (HRS) 2024 annual meeting.

The PREDIMAR study enrolled 720 patients from the larger PREDIMED study, which showed that patients without AF at enrollment and who followed a Mediterranean diet enriched with EVOO had a 38% lower rate of incidental AF than control individuals.

PREDIMAR evaluated the impact of the diet on arrhythmia recurrence in patients after ablation. The patients were randomized in a 1:1 ratio to either the dietary intervention group or the control group.
 

PREDIMAR Study Results

The overall difference in the rate of AF recurrence in the 3-18 months after ablation between the dietary intervention and control groups was nonsignificant (34.8% vs 37.5%).

However, among the 431 patients with paroxysmal AF, 25.2% in the diet group and 34.7% in the control group had no tachyarrhythmia recurrence, which translates into a 31% lower risk in the diet group.

In this study, the diet was rich in fish, nuts, fruits, and vegetables and was complemented with EVOO. Participants were also permitted moderate wine consumption.

The intervention involved dietitians who remotely followed patients and made periodic telephone calls to encourage them to stay on the diet. Participants had weight and body measurements taken at baseline and at 3, 6, 12, and 18 months and underwent an ECG at 6, 12, and 18 months. Labs were obtained at baseline and at 12 months. Participants were also given educational materials throughout the intervention.

Average scores, based on a scale of 0-13, excluding an item for wine intake, were 7.8 in the diet group and 7.2 in the control group.

Daily average alcohol intake was higher in the diet group than in the control group (9.8 vs 8.2 g), but “the weight of the patient during the study didn’t change in any group,” Dr. Barrio-Lopez reported.

Baseline characteristics were similar in the two groups. About 60% were taking antiarrhythmic drugs, and about 84% were taking anticoagulants.
 

‘A Tour de Force’

PREDIMAR was “really a tour de force,” Christine Albert, MD, MPH, chair of cardiology at the Smidt Heart Institute at the Cedars-Sinai Medical Center in Los Angeles, California, said during a commentary presented at HRS. “We talk about how we’re going to do these dietary interventions and weight loss and all the risk-factor reduction, and they pulled it off with 700 individuals and also did it in a way that was very novel.”

This is the first large-scale dietary intervention trial of patients with AF. However, Dr. Albert noted later in an interview, the Mediterranean diet poses potential challenges for some people with AF.

“The Mediterranean diet recommends that people drink wine, but then there’s clear evidence that abstinence from alcohol actually reduces recurrences of atrial fibrillation, so even though there are a lot of things about the Mediterranean diet that are probably healthy and good for atrial fibrillation, that aspect of it might be working against the patient,” she explained.

The finding that patients in the Mediterranean diet group experienced no significant weight loss could be counterintuitive when it comes to preventing AF. But “you could adapt the diet for AF,” Dr. Albert said. You could “leave out the wine and focus more on weight loss if the patient is obese because those are also the pillars of what we’ve learned for patients with atrial fibrillation.”

Making weight loss a key component of the study could be significant for the American population. “At least in the United States, that’s a huge part of the risk factors for atrial fibrillation after ablation,” she said.

The remote follow-up component of the PREDIMAR study is also intriguing. “I think what’s most exciting about what they did is, they showed they can do all these things remotely,” Dr. Albert added.

Dr. Barrio-Lopez had no relevant financial relationships. Dr. Albert disclosed relationships with Abbott, Roche Diagnostics, St. Jude Medical, Boston Scientific, Medtronic, and Element Science.

A version of this article appeared on Medscape.com.

WASHINGTON – Women with autoimmune liver diseases (AILD) may face increased risks for major adverse cardiovascular outcomes, according to a study presented at the annual Digestive Disease Week^® (DDW).

In particular, women with autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) appear to have higher risks than women without AIH or PBC. Those with primary sclerosing cholangitis (PSC) don’t seem to have increased risks.

“We know that cardiovascular disease remains the number one cause of death, but the mortality rate for women over the last decade has plateaued, whereas in men it’s actually declining due to interventions,” said lead author Rachel Redfield, MD, a transplant hepatology fellow at Thomas Jefferson University Hospital in Philadelphia.

“This is likely because we don’t have adequate risk stratification, especially for women,” she said. “We know that immune-mediated diseases — such as rheumatoid arthritis and psoriasis — carry a higher risk of cardiovascular disease, but there’s not a lot of data on our autoimmune liver disease patients.”

Dr. Redfield

Although being a female can offer protection against some CVD risks, the atherosclerotic cardiovascular disease (ASCVD) 10-year risk score calculator recommended by the American College of Cardiology doesn’t include chronic inflammatory diseases associated with increased CVD risk, including AILD.

Dr. Redfield and colleagues conducted a multicenter, retrospective cohort study of patients with AIH, PBC, and PSC from 1999-2019. Using TriNetX data, the researchers looked at women with AILD who also had diabetes mellitus, hypertension, and hyperlipidemia, as well as a control group of men and women with these same disorders, excluding those who used biologics, immune modulators, and steroids or had other autoimmune disorders.

The research team used 1:1 propensity-score matching for women in the study group and in the control group based on age, race, ethnicity, ASCVD risk factors, and tobacco use. Women in the study group and men in the control group were matched for age, race, ethnicity, and tobacco use.

The primary outcome was summative cardiovascular risk, including unstable angina, acute myocardial infarction, presence of coronary angioplasty implant, coronary artery bypass, percutaneous coronary intervention, and cerebral infarction.

Overall, women with AIH had a significantly higher cardiovascular risk compared to women without AIH, at 25.4% versus 20.6% (P = .0007).

Specifically, women with PBC had a significantly higher cardiovascular risk compared to women without PBC, at 27.05% versus 20.9% (P < .0001).

There wasn’t a significant difference in risk between women with and without PSC, at 27.5% versus 21.8% (P = .27).

When compared to men without disease, women with AIH didn’t have a statistically significant higher risk, at 25.3% versus 24.2% (P = .44). Similarly, there didn’t appear to be a significant difference between women with PBC and men without PBC, at 26.9% versus 25.9% (P = .52), or between women with PSC and men without PSC, at 27.7% versus 26.2% (P = .78).

Dr. Redfield and colleagues then compared the ASCVD-calculated risk versus database risk, finding that in each group of women with AILD — including AIH, PBC, and PSC — the ASCVD-calculated risk was around 11%, compared with database risk scores of 25% for AIH, 27% for PBC, and 28% for PSC. These database risks appeared similar to both the ASCVD and database risk percentages for men.

“So potentially there’s an oversight in women with any kind of inflammatory disease, but specifically here, autoimmune liver diseases,” she said. “We really need to enhance our risk assessment strategies to take into account their risk and optimize patient outcomes.”

Dr. Redfield noted the limitations with using TriNetX data, including coding consistency among providers and healthcare organizations, unknown patient follow-up dates, and the inability to capture various inflammatory disease phenotypes, such as autoimmune hepatitis with multiple flares, which may be associated with higher cardiovascular risks.

As an attendee of the DDW session, Kenneth Kelson, MD, a gastroenterologist with Fremont Medical Group and Washington Hospital Healthcare System in Fremont, California, noted the importance of investigating the effects of different types of statins in these patients. Although the research team looked at top-level differences among statin users, finding that women with AILD were more likely to be on a statin, they didn’t incorporate statin therapy in the propensity-score matching model.

“Lipid-soluble statins are known to cause more liver trouble, even though it’s pretty low,” Dr. Kelson said. “Whereas the water-soluble statins have a lower incidence of liver issues.”

Dr. Redfield and Dr. Kelson reported no relevant disclosures.

WASHINGTON – Women with autoimmune liver diseases (AILD) may face increased risks for major adverse cardiovascular outcomes, according to a study presented at the annual Digestive Disease Week^® (DDW).

In particular, women with autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) appear to have higher risks than women without AIH or PBC. Those with primary sclerosing cholangitis (PSC) don’t seem to have increased risks.

“We know that cardiovascular disease remains the number one cause of death, but the mortality rate for women over the last decade has plateaued, whereas in men it’s actually declining due to interventions,” said lead author Rachel Redfield, MD, a transplant hepatology fellow at Thomas Jefferson University Hospital in Philadelphia.

“This is likely because we don’t have adequate risk stratification, especially for women,” she said. “We know that immune-mediated diseases — such as rheumatoid arthritis and psoriasis — carry a higher risk of cardiovascular disease, but there’s not a lot of data on our autoimmune liver disease patients.”

Dr. Redfield

Although being a female can offer protection against some CVD risks, the atherosclerotic cardiovascular disease (ASCVD) 10-year risk score calculator recommended by the American College of Cardiology doesn’t include chronic inflammatory diseases associated with increased CVD risk, including AILD.

Dr. Redfield and colleagues conducted a multicenter, retrospective cohort study of patients with AIH, PBC, and PSC from 1999-2019. Using TriNetX data, the researchers looked at women with AILD who also had diabetes mellitus, hypertension, and hyperlipidemia, as well as a control group of men and women with these same disorders, excluding those who used biologics, immune modulators, and steroids or had other autoimmune disorders.

The research team used 1:1 propensity-score matching for women in the study group and in the control group based on age, race, ethnicity, ASCVD risk factors, and tobacco use. Women in the study group and men in the control group were matched for age, race, ethnicity, and tobacco use.

The primary outcome was summative cardiovascular risk, including unstable angina, acute myocardial infarction, presence of coronary angioplasty implant, coronary artery bypass, percutaneous coronary intervention, and cerebral infarction.

Overall, women with AIH had a significantly higher cardiovascular risk compared to women without AIH, at 25.4% versus 20.6% (P = .0007).

Specifically, women with PBC had a significantly higher cardiovascular risk compared to women without PBC, at 27.05% versus 20.9% (P < .0001).

There wasn’t a significant difference in risk between women with and without PSC, at 27.5% versus 21.8% (P = .27).

When compared to men without disease, women with AIH didn’t have a statistically significant higher risk, at 25.3% versus 24.2% (P = .44). Similarly, there didn’t appear to be a significant difference between women with PBC and men without PBC, at 26.9% versus 25.9% (P = .52), or between women with PSC and men without PSC, at 27.7% versus 26.2% (P = .78).

Dr. Redfield and colleagues then compared the ASCVD-calculated risk versus database risk, finding that in each group of women with AILD — including AIH, PBC, and PSC — the ASCVD-calculated risk was around 11%, compared with database risk scores of 25% for AIH, 27% for PBC, and 28% for PSC. These database risks appeared similar to both the ASCVD and database risk percentages for men.

“So potentially there’s an oversight in women with any kind of inflammatory disease, but specifically here, autoimmune liver diseases,” she said. “We really need to enhance our risk assessment strategies to take into account their risk and optimize patient outcomes.”

Dr. Redfield noted the limitations with using TriNetX data, including coding consistency among providers and healthcare organizations, unknown patient follow-up dates, and the inability to capture various inflammatory disease phenotypes, such as autoimmune hepatitis with multiple flares, which may be associated with higher cardiovascular risks.

As an attendee of the DDW session, Kenneth Kelson, MD, a gastroenterologist with Fremont Medical Group and Washington Hospital Healthcare System in Fremont, California, noted the importance of investigating the effects of different types of statins in these patients. Although the research team looked at top-level differences among statin users, finding that women with AILD were more likely to be on a statin, they didn’t incorporate statin therapy in the propensity-score matching model.

“Lipid-soluble statins are known to cause more liver trouble, even though it’s pretty low,” Dr. Kelson said. “Whereas the water-soluble statins have a lower incidence of liver issues.”

Dr. Redfield and Dr. Kelson reported no relevant disclosures.

WASHINGTON – Women with autoimmune liver diseases (AILD) may face increased risks for major adverse cardiovascular outcomes, according to a study presented at the annual Digestive Disease Week^® (DDW).

In particular, women with autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) appear to have higher risks than women without AIH or PBC. Those with primary sclerosing cholangitis (PSC) don’t seem to have increased risks.

“We know that cardiovascular disease remains the number one cause of death, but the mortality rate for women over the last decade has plateaued, whereas in men it’s actually declining due to interventions,” said lead author Rachel Redfield, MD, a transplant hepatology fellow at Thomas Jefferson University Hospital in Philadelphia.

“This is likely because we don’t have adequate risk stratification, especially for women,” she said. “We know that immune-mediated diseases — such as rheumatoid arthritis and psoriasis — carry a higher risk of cardiovascular disease, but there’s not a lot of data on our autoimmune liver disease patients.”

Dr. Redfield

Although being a female can offer protection against some CVD risks, the atherosclerotic cardiovascular disease (ASCVD) 10-year risk score calculator recommended by the American College of Cardiology doesn’t include chronic inflammatory diseases associated with increased CVD risk, including AILD.

Dr. Redfield and colleagues conducted a multicenter, retrospective cohort study of patients with AIH, PBC, and PSC from 1999-2019. Using TriNetX data, the researchers looked at women with AILD who also had diabetes mellitus, hypertension, and hyperlipidemia, as well as a control group of men and women with these same disorders, excluding those who used biologics, immune modulators, and steroids or had other autoimmune disorders.

The research team used 1:1 propensity-score matching for women in the study group and in the control group based on age, race, ethnicity, ASCVD risk factors, and tobacco use. Women in the study group and men in the control group were matched for age, race, ethnicity, and tobacco use.

The primary outcome was summative cardiovascular risk, including unstable angina, acute myocardial infarction, presence of coronary angioplasty implant, coronary artery bypass, percutaneous coronary intervention, and cerebral infarction.

Overall, women with AIH had a significantly higher cardiovascular risk compared to women without AIH, at 25.4% versus 20.6% (P = .0007).

Specifically, women with PBC had a significantly higher cardiovascular risk compared to women without PBC, at 27.05% versus 20.9% (P < .0001).

There wasn’t a significant difference in risk between women with and without PSC, at 27.5% versus 21.8% (P = .27).

When compared to men without disease, women with AIH didn’t have a statistically significant higher risk, at 25.3% versus 24.2% (P = .44). Similarly, there didn’t appear to be a significant difference between women with PBC and men without PBC, at 26.9% versus 25.9% (P = .52), or between women with PSC and men without PSC, at 27.7% versus 26.2% (P = .78).

Dr. Redfield and colleagues then compared the ASCVD-calculated risk versus database risk, finding that in each group of women with AILD — including AIH, PBC, and PSC — the ASCVD-calculated risk was around 11%, compared with database risk scores of 25% for AIH, 27% for PBC, and 28% for PSC. These database risks appeared similar to both the ASCVD and database risk percentages for men.

“So potentially there’s an oversight in women with any kind of inflammatory disease, but specifically here, autoimmune liver diseases,” she said. “We really need to enhance our risk assessment strategies to take into account their risk and optimize patient outcomes.”

Dr. Redfield noted the limitations with using TriNetX data, including coding consistency among providers and healthcare organizations, unknown patient follow-up dates, and the inability to capture various inflammatory disease phenotypes, such as autoimmune hepatitis with multiple flares, which may be associated with higher cardiovascular risks.

As an attendee of the DDW session, Kenneth Kelson, MD, a gastroenterologist with Fremont Medical Group and Washington Hospital Healthcare System in Fremont, California, noted the importance of investigating the effects of different types of statins in these patients. Although the research team looked at top-level differences among statin users, finding that women with AILD were more likely to be on a statin, they didn’t incorporate statin therapy in the propensity-score matching model.

“Lipid-soluble statins are known to cause more liver trouble, even though it’s pretty low,” Dr. Kelson said. “Whereas the water-soluble statins have a lower incidence of liver issues.”

Dr. Redfield and Dr. Kelson reported no relevant disclosures.

BOSTON — Patients who have had a stroke are thought to be at a higher risk for another one, but oral anticoagulation with edoxaban led to no discernible reduction in the risk for a second stroke, and the risk for major bleeding was more than quadruple the risk with no anticoagulation, a subanalysis of a major European trial has shown.

“There is no interaction between prior stroke or TIA [transient ischemic attack] and the treatment effect, and this is true for the primary outcome and the safety outcome,” Paulus Kirchoff, MD, director of cardiology at the University Heart and Vascular Center in Hamburg, Germany, said during his presentation of a subanalysis of the NOAH-AFNET 6 trial at the annual meeting of the Heart Rhythm Society (HRS) 2024. However, “there is a signal for more safety events in patients randomized to anticoagulation with a prior stroke.”

The subanalysis involved 253 patients who had had a stroke or TIA and who had device-detected atrial fibrillation (AF) from the overall NOAH-AFNET 6 population of 2536 patients, which enrolled patients 65 years and older with at least one additional CHA2DS-VASc risk factor and patients 75 years and older with device-detected subclinical AF episodes of at least 6 minutes. Patients were randomized to either edoxaban or no anticoagulation, but 53.9% of the no-anticoagulation group was taking aspirin at trial enrollment. Anticoagulation with edoxaban was shown to have no significant impact on stroke rates or other cardiovascular outcomes.
 

Subanalysis Results

In the subanalysis, a composite of stroke, systemic embolism, and cardiovascular death — the primary outcome — was similar in the edoxaban and no-anticoagulation groups (14/122 patients [11.5%] vs 16/131 patients [12.2%]; 5.7% vs 6.3% per patient-year).

The rate of recurrent stroke was also similar in the edoxaban and no-anticoagulation groups (4 of 122 patients [3.3%] vs 6 of 131 patients [4.6%]; 1.6% vs 2.3% per patient-year). And there were eight cardiovascular deaths in each group.

However, edoxaban patients had significantly higher rates of major bleeding.

“This is a subanalysis, so what we see in terms of the number of patients with events is not powered for a definitive answer, but we do see that there were 10 major bleeds in the group of patients with a prior stroke or TIA in NOAH,” Dr. Kirchoff reported. “Eight of those 10 major bleeds occurred in patients randomized to edoxaban.”

Results from the NOAH-AFNET 6 trial have been compared with those from the ARTESiA trial, which compared apixaban anticoagulation with aspirin in patients with subclinical AF and was also presented at HRS 2024. ARTESiA showed that apixaban significantly lowered the risk for stroke and systemic embolism.

“In ARTESiA, everyone was on aspirin when they were randomized to no anticoagulation; in NOAH, only about half were on aspirin,” Dr. Kirchoff said.

Both studies had similar outcomes for cardiovascular death in the anticoagulation and no-anticoagulation groups. “It’s not significant; it may be chance, but it’s definitely not the reduction in death that we have seen in the anticoagulant trials,” Dr. Kirchoff said. “When you look at the meta-analyses of the early anticoagulation trials, there’s a one third reduction in death, and here we’re talking about a smaller reduction.”

This research points to a need for a better way to evaluate stroke risk. “We need new markers,” Dr. Kirchoff said. “Some of them may be in the blood or imaging, genetics maybe, and one thing that really emerges from my perspective is that we now have the first evidence to suggest that patients with a very low atrial fibrillation burden have a low stroke rate.”

More research is needed to better understand AF characteristics and stroke risk, he said.
 

AF Care Enters a ‘Gray Zone’

The NOAH-AFNET 6 results, coupled with those from ARTESiA, are changing the paradigm for anticoagulation in patients with stroke, said Taya Glotzer, MD, an electrophysiologist at the Hackensack University Medical Center in Hackensack, New Jersey, who compiled her own analysis of the studies’ outcomes.

“In ARTESiA, the stroke reduction was only 0.44% a year, with a number needed to treat of 250,” she said. “In the NOAH-AFNET 6 main trial, the stroke reduction was 0.2%, with the number needed to treat of 500, and in the NOAH prior stroke patients, there was a 0.7% reduction, with a number needed to treat of 143.”

None of these trials would meet the standard for a class 1 recommendation for anticoagulation with a reduction of even 1%-2% per year, she noted, but they do show that the stroke rate “is very, very low” in prior patients with stroke.

“Prior to 2024, we knew what was black and white; we knew who to anticoagulate and who not to anticoagulate. And now we are in a gray zone, trying to balance the risk of stroke and bleeding. We have to individualize or hope for substudies, perhaps using the CHA2DS-VASc score or other information about the left atrium, to help us make decisions in these patients. It’s not just going to be black and white,” she said.

Dr. Kirchoff had no relevant financial relationships to disclose. Dr. Glotzer disclosed financial relationships with Medtronic, Abbott, Boston Scientific, and MediaSphere Medical.

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

BOSTON — Patients who have had a stroke are thought to be at a higher risk for another one, but oral anticoagulation with edoxaban led to no discernible reduction in the risk for a second stroke, and the risk for major bleeding was more than quadruple the risk with no anticoagulation, a subanalysis of a major European trial has shown.

“There is no interaction between prior stroke or TIA [transient ischemic attack] and the treatment effect, and this is true for the primary outcome and the safety outcome,” Paulus Kirchoff, MD, director of cardiology at the University Heart and Vascular Center in Hamburg, Germany, said during his presentation of a subanalysis of the NOAH-AFNET 6 trial at the annual meeting of the Heart Rhythm Society (HRS) 2024. However, “there is a signal for more safety events in patients randomized to anticoagulation with a prior stroke.”

The subanalysis involved 253 patients who had had a stroke or TIA and who had device-detected atrial fibrillation (AF) from the overall NOAH-AFNET 6 population of 2536 patients, which enrolled patients 65 years and older with at least one additional CHA2DS-VASc risk factor and patients 75 years and older with device-detected subclinical AF episodes of at least 6 minutes. Patients were randomized to either edoxaban or no anticoagulation, but 53.9% of the no-anticoagulation group was taking aspirin at trial enrollment. Anticoagulation with edoxaban was shown to have no significant impact on stroke rates or other cardiovascular outcomes.
 

Subanalysis Results

In the subanalysis, a composite of stroke, systemic embolism, and cardiovascular death — the primary outcome — was similar in the edoxaban and no-anticoagulation groups (14/122 patients [11.5%] vs 16/131 patients [12.2%]; 5.7% vs 6.3% per patient-year).

The rate of recurrent stroke was also similar in the edoxaban and no-anticoagulation groups (4 of 122 patients [3.3%] vs 6 of 131 patients [4.6%]; 1.6% vs 2.3% per patient-year). And there were eight cardiovascular deaths in each group.

However, edoxaban patients had significantly higher rates of major bleeding.

“This is a subanalysis, so what we see in terms of the number of patients with events is not powered for a definitive answer, but we do see that there were 10 major bleeds in the group of patients with a prior stroke or TIA in NOAH,” Dr. Kirchoff reported. “Eight of those 10 major bleeds occurred in patients randomized to edoxaban.”

Results from the NOAH-AFNET 6 trial have been compared with those from the ARTESiA trial, which compared apixaban anticoagulation with aspirin in patients with subclinical AF and was also presented at HRS 2024. ARTESiA showed that apixaban significantly lowered the risk for stroke and systemic embolism.

“In ARTESiA, everyone was on aspirin when they were randomized to no anticoagulation; in NOAH, only about half were on aspirin,” Dr. Kirchoff said.

Both studies had similar outcomes for cardiovascular death in the anticoagulation and no-anticoagulation groups. “It’s not significant; it may be chance, but it’s definitely not the reduction in death that we have seen in the anticoagulant trials,” Dr. Kirchoff said. “When you look at the meta-analyses of the early anticoagulation trials, there’s a one third reduction in death, and here we’re talking about a smaller reduction.”

This research points to a need for a better way to evaluate stroke risk. “We need new markers,” Dr. Kirchoff said. “Some of them may be in the blood or imaging, genetics maybe, and one thing that really emerges from my perspective is that we now have the first evidence to suggest that patients with a very low atrial fibrillation burden have a low stroke rate.”

More research is needed to better understand AF characteristics and stroke risk, he said.
 

AF Care Enters a ‘Gray Zone’

The NOAH-AFNET 6 results, coupled with those from ARTESiA, are changing the paradigm for anticoagulation in patients with stroke, said Taya Glotzer, MD, an electrophysiologist at the Hackensack University Medical Center in Hackensack, New Jersey, who compiled her own analysis of the studies’ outcomes.

“In ARTESiA, the stroke reduction was only 0.44% a year, with a number needed to treat of 250,” she said. “In the NOAH-AFNET 6 main trial, the stroke reduction was 0.2%, with the number needed to treat of 500, and in the NOAH prior stroke patients, there was a 0.7% reduction, with a number needed to treat of 143.”

None of these trials would meet the standard for a class 1 recommendation for anticoagulation with a reduction of even 1%-2% per year, she noted, but they do show that the stroke rate “is very, very low” in prior patients with stroke.

“Prior to 2024, we knew what was black and white; we knew who to anticoagulate and who not to anticoagulate. And now we are in a gray zone, trying to balance the risk of stroke and bleeding. We have to individualize or hope for substudies, perhaps using the CHA2DS-VASc score or other information about the left atrium, to help us make decisions in these patients. It’s not just going to be black and white,” she said.

Dr. Kirchoff had no relevant financial relationships to disclose. Dr. Glotzer disclosed financial relationships with Medtronic, Abbott, Boston Scientific, and MediaSphere Medical.

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

BOSTON — Patients who have had a stroke are thought to be at a higher risk for another one, but oral anticoagulation with edoxaban led to no discernible reduction in the risk for a second stroke, and the risk for major bleeding was more than quadruple the risk with no anticoagulation, a subanalysis of a major European trial has shown.

“There is no interaction between prior stroke or TIA [transient ischemic attack] and the treatment effect, and this is true for the primary outcome and the safety outcome,” Paulus Kirchoff, MD, director of cardiology at the University Heart and Vascular Center in Hamburg, Germany, said during his presentation of a subanalysis of the NOAH-AFNET 6 trial at the annual meeting of the Heart Rhythm Society (HRS) 2024. However, “there is a signal for more safety events in patients randomized to anticoagulation with a prior stroke.”

The subanalysis involved 253 patients who had had a stroke or TIA and who had device-detected atrial fibrillation (AF) from the overall NOAH-AFNET 6 population of 2536 patients, which enrolled patients 65 years and older with at least one additional CHA2DS-VASc risk factor and patients 75 years and older with device-detected subclinical AF episodes of at least 6 minutes. Patients were randomized to either edoxaban or no anticoagulation, but 53.9% of the no-anticoagulation group was taking aspirin at trial enrollment. Anticoagulation with edoxaban was shown to have no significant impact on stroke rates or other cardiovascular outcomes.
 

Subanalysis Results

In the subanalysis, a composite of stroke, systemic embolism, and cardiovascular death — the primary outcome — was similar in the edoxaban and no-anticoagulation groups (14/122 patients [11.5%] vs 16/131 patients [12.2%]; 5.7% vs 6.3% per patient-year).

The rate of recurrent stroke was also similar in the edoxaban and no-anticoagulation groups (4 of 122 patients [3.3%] vs 6 of 131 patients [4.6%]; 1.6% vs 2.3% per patient-year). And there were eight cardiovascular deaths in each group.

However, edoxaban patients had significantly higher rates of major bleeding.

“This is a subanalysis, so what we see in terms of the number of patients with events is not powered for a definitive answer, but we do see that there were 10 major bleeds in the group of patients with a prior stroke or TIA in NOAH,” Dr. Kirchoff reported. “Eight of those 10 major bleeds occurred in patients randomized to edoxaban.”

Results from the NOAH-AFNET 6 trial have been compared with those from the ARTESiA trial, which compared apixaban anticoagulation with aspirin in patients with subclinical AF and was also presented at HRS 2024. ARTESiA showed that apixaban significantly lowered the risk for stroke and systemic embolism.

“In ARTESiA, everyone was on aspirin when they were randomized to no anticoagulation; in NOAH, only about half were on aspirin,” Dr. Kirchoff said.

Both studies had similar outcomes for cardiovascular death in the anticoagulation and no-anticoagulation groups. “It’s not significant; it may be chance, but it’s definitely not the reduction in death that we have seen in the anticoagulant trials,” Dr. Kirchoff said. “When you look at the meta-analyses of the early anticoagulation trials, there’s a one third reduction in death, and here we’re talking about a smaller reduction.”

This research points to a need for a better way to evaluate stroke risk. “We need new markers,” Dr. Kirchoff said. “Some of them may be in the blood or imaging, genetics maybe, and one thing that really emerges from my perspective is that we now have the first evidence to suggest that patients with a very low atrial fibrillation burden have a low stroke rate.”

More research is needed to better understand AF characteristics and stroke risk, he said.
 

AF Care Enters a ‘Gray Zone’

The NOAH-AFNET 6 results, coupled with those from ARTESiA, are changing the paradigm for anticoagulation in patients with stroke, said Taya Glotzer, MD, an electrophysiologist at the Hackensack University Medical Center in Hackensack, New Jersey, who compiled her own analysis of the studies’ outcomes.

“In ARTESiA, the stroke reduction was only 0.44% a year, with a number needed to treat of 250,” she said. “In the NOAH-AFNET 6 main trial, the stroke reduction was 0.2%, with the number needed to treat of 500, and in the NOAH prior stroke patients, there was a 0.7% reduction, with a number needed to treat of 143.”

None of these trials would meet the standard for a class 1 recommendation for anticoagulation with a reduction of even 1%-2% per year, she noted, but they do show that the stroke rate “is very, very low” in prior patients with stroke.

“Prior to 2024, we knew what was black and white; we knew who to anticoagulate and who not to anticoagulate. And now we are in a gray zone, trying to balance the risk of stroke and bleeding. We have to individualize or hope for substudies, perhaps using the CHA2DS-VASc score or other information about the left atrium, to help us make decisions in these patients. It’s not just going to be black and white,” she said.

Dr. Kirchoff had no relevant financial relationships to disclose. Dr. Glotzer disclosed financial relationships with Medtronic, Abbott, Boston Scientific, and MediaSphere Medical.

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

LISBON, PORTUGAL — Few people with suspected heart failure and elevated N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels are receiving a diagnosis after a year, reported investigators, who say high rates of hospitalization are common.

Presenting here at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2024, researchers shared results from the REVOLUTION-HF study involving almost 8000 people who consulted outpatient primary and secondary care over a 5-year period.

About two thirds of the patients had suspected heart failure; however, less than 30% of the people received a diagnosis within a year.

Yet hospitalization was eight times higher in the suspected heart failure group than in the control group, and all-cause mortality was nearly doubled. The outcomes were even worse in patients with high NT-proBNP levels.

Patients with suspected heart failure are “waiting far too long to see a specialist, and that results in a delay to guideline-directed medical therapy, despite the fact that we’re perfectly happy to slap them all on diuretics,” said study presenter Lisa Anderson, MD, PhD, Cardiovascular Clinical Academic Group, Molecular and Clinical Sciences Research Institute, St George’s Hospital, University of London, England.

“We need to rethink our management of heart failure patients presenting in the community,” she said.

A big gap exists internationally between presentation with heart failure, an elevated NT-proBNP, and confirmatory specialist assessment, she explained.

“It’s a scandal that patients are coming to the GP with signs and symptoms of heart failure, they get tested for natriuretic peptides, and nothing happens,” said co-author Antoni Bayés-Genís, MD, PhD, Heart Institute director, Hospital Universitari Germans Trias i Pujol Catedràtic, Barcelona, Spain.

“These patients may receive an echo, or not, in the coming 12 months,” and “during these 12 months, there is a huge number of heart failure hospitalizations and deaths that could probably be prevented.”
 

Why the Reluctance to Diagnose?

Many issues get in the way of early diagnosis, Dr. Bayés-Genís said. “Inertia, comorbidities, ageism.”

A lot of patients with heart failure are elderly women with some degree of weight gain, he said. “And they come to the clinic with fatigue, so we tell them, ‘Well, that’s normal.”

But “it may not be normal,” he added. “This is a very important topic that we, as a society, need to address.”

There are several “misconceptions” about heart failure, said Ileana L. Piña, MD, MPH, the Robert Stein Chair for Quality and Safety, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, who was not involved in the study.

For example, “we’re all convinced that guideline-directed medical therapy works,” but the evidence is only for patients “with a diagnosis.” In addition, “millions of patients get tested” for heart failure, but they already have a “known diagnosis.”

“When we study these drugs, we’re studying them on patients with manifest disease,” who are only then randomized, Dr. Piña said. “But we seldom see them while they’re developing heart failure. And it’s a process; it doesn’t happen overnight.”

Patients initially often think they may have asthma, and so what follows is an extended period of “uncertainty” and “important time lost” before they finally undergo the assessments that show that they have heart failure, she said.

However, “uncertainty” often lands a patient “in the emergency room or with an unscheduled office visit, where NT-proBNP might get ordered and there’s a long lineup for an echo.”

There are several strengths of the current study, Dr. Piña said, including the fact that 50% of the study population were women, and they were older than a typical trial population. Nevertheless, the results were “eye-opening but not surprising” and, in the end, “disappointing.”

“I agree, we need a revolution, Dr. Anderson,” Dr. Piña said. “The revolution of paying attention to the NT-proBNP when you get it and it’s elevated” and then following through with echocardiography and starting “guideline-directed medical therapy early.”

The diagnosis of heart failure “relies on the presentation of patients with nonspecific signs and symptoms,” such as dyspnea and peripheral edema, “but initiation of guideline-directed medical therapy — life-saving treatment — has to wait until we have a formal echocardiography and specialist clinician assessment,” Dr. Anderson said.

The latest clinical consensus statement from the Heart Failure Association “proposes both rule-in and rule-out NT-proBNP levels for heart failure diagnosis, and obviously we all recognize that it’s important to treat patients as soon as they’re diagnosed,” she explained.
 

REVOLUTION-HF

To examine the risk profile for patients presenting to outpatient care with suspected heart failure, the researchers conducted REVOLUTION-HF, which leveraged nationwide Swedish linked data from general practices, specialists, pharmacies, hospitals, and cause of death registers.

“Really impressively, most of these NT-proBNP tests were coming back within a day,” Dr. Anderson said, “so a really, really good turnaround.”

Individuals were excluded if they had an inpatient admission, echocardiography, or heart failure diagnosis between presentation and the NT-proBNP measurement.

These people were then compared with those presenting to primary or secondary outpatient care for any reason and matched for age, sex, care level, and index year. Both groups were followed up for 1 year.

“Despite this really impressive, almost immediate NT-proBNP testing,” the waiting times to undergo echocardiography were “really disappointing,” Dr. Anderson said.

The median time to first registered echocardiography was 40 days, and only 29% of patients with suspected heart failure received a diagnosis within a year of the index presentation date, which she described as “inadequately slow.”

“And how does this translate to medical therapy?” she asked.
 

Heart Failure Drugs

After the index presentation, the rate of loop diuretic use quadrupled among individuals suspected of having heart failure, but there was a “muted response” when it came to the prescribing of beta-blockers and the other pillars of heart failure therapy, which Dr. Anderson called “very disappointing.”

For outcomes after the index presentation, the rate of hospitalization was much higher in the group with suspected heart failure than in the control group (16.1 vs 2.2 events per 100 person-years). And all-cause mortality occurred more often in the group with suspected heart failure than in the control group (10.3 vs 6.5 events per 100 person-years).

Among patients with NT-proBNP levels of 2000 ng/L, there was a “rapid” onset of hospitalization “within the first few days” of the index presentation, which was tracked by a more linear rise in all-cause deaths, Dr. Anderson reported.

In the United Kingdom, “we are very proud of our 2- and 6-week pathways,” which stipulate that suspected heart failure patients with NT-proBNP levels between 400 and 2000 ng/L are to have a specialist assessment and transthoracic echocardiography within 6 weeks; for those with levels > 2000 ng/L, that interval is accelerated to 2 weeks, she said.

The current results show that “2 weeks is too slow.” And looking at the rest of the cohort with lower NT-proBNP levels, “patients have already been admitted and died” by 6 weeks, she said.

When patients are stratified by age, “you get exactly what you would expect,” Dr. Anderson said. “The older patients are the most at risk” for both hospitalization and all-cause mortality.
 

A version of this article appeared on Medscape.com.

LISBON, PORTUGAL — Few people with suspected heart failure and elevated N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels are receiving a diagnosis after a year, reported investigators, who say high rates of hospitalization are common.

Presenting here at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2024, researchers shared results from the REVOLUTION-HF study involving almost 8000 people who consulted outpatient primary and secondary care over a 5-year period.

About two thirds of the patients had suspected heart failure; however, less than 30% of the people received a diagnosis within a year.

Yet hospitalization was eight times higher in the suspected heart failure group than in the control group, and all-cause mortality was nearly doubled. The outcomes were even worse in patients with high NT-proBNP levels.

Patients with suspected heart failure are “waiting far too long to see a specialist, and that results in a delay to guideline-directed medical therapy, despite the fact that we’re perfectly happy to slap them all on diuretics,” said study presenter Lisa Anderson, MD, PhD, Cardiovascular Clinical Academic Group, Molecular and Clinical Sciences Research Institute, St George’s Hospital, University of London, England.

“We need to rethink our management of heart failure patients presenting in the community,” she said.

A big gap exists internationally between presentation with heart failure, an elevated NT-proBNP, and confirmatory specialist assessment, she explained.

“It’s a scandal that patients are coming to the GP with signs and symptoms of heart failure, they get tested for natriuretic peptides, and nothing happens,” said co-author Antoni Bayés-Genís, MD, PhD, Heart Institute director, Hospital Universitari Germans Trias i Pujol Catedràtic, Barcelona, Spain.

“These patients may receive an echo, or not, in the coming 12 months,” and “during these 12 months, there is a huge number of heart failure hospitalizations and deaths that could probably be prevented.”
 

Why the Reluctance to Diagnose?

Many issues get in the way of early diagnosis, Dr. Bayés-Genís said. “Inertia, comorbidities, ageism.”

A lot of patients with heart failure are elderly women with some degree of weight gain, he said. “And they come to the clinic with fatigue, so we tell them, ‘Well, that’s normal.”

But “it may not be normal,” he added. “This is a very important topic that we, as a society, need to address.”

There are several “misconceptions” about heart failure, said Ileana L. Piña, MD, MPH, the Robert Stein Chair for Quality and Safety, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, who was not involved in the study.

For example, “we’re all convinced that guideline-directed medical therapy works,” but the evidence is only for patients “with a diagnosis.” In addition, “millions of patients get tested” for heart failure, but they already have a “known diagnosis.”

“When we study these drugs, we’re studying them on patients with manifest disease,” who are only then randomized, Dr. Piña said. “But we seldom see them while they’re developing heart failure. And it’s a process; it doesn’t happen overnight.”

Patients initially often think they may have asthma, and so what follows is an extended period of “uncertainty” and “important time lost” before they finally undergo the assessments that show that they have heart failure, she said.

However, “uncertainty” often lands a patient “in the emergency room or with an unscheduled office visit, where NT-proBNP might get ordered and there’s a long lineup for an echo.”

There are several strengths of the current study, Dr. Piña said, including the fact that 50% of the study population were women, and they were older than a typical trial population. Nevertheless, the results were “eye-opening but not surprising” and, in the end, “disappointing.”

“I agree, we need a revolution, Dr. Anderson,” Dr. Piña said. “The revolution of paying attention to the NT-proBNP when you get it and it’s elevated” and then following through with echocardiography and starting “guideline-directed medical therapy early.”

The diagnosis of heart failure “relies on the presentation of patients with nonspecific signs and symptoms,” such as dyspnea and peripheral edema, “but initiation of guideline-directed medical therapy — life-saving treatment — has to wait until we have a formal echocardiography and specialist clinician assessment,” Dr. Anderson said.

The latest clinical consensus statement from the Heart Failure Association “proposes both rule-in and rule-out NT-proBNP levels for heart failure diagnosis, and obviously we all recognize that it’s important to treat patients as soon as they’re diagnosed,” she explained.
 

REVOLUTION-HF

To examine the risk profile for patients presenting to outpatient care with suspected heart failure, the researchers conducted REVOLUTION-HF, which leveraged nationwide Swedish linked data from general practices, specialists, pharmacies, hospitals, and cause of death registers.

“Really impressively, most of these NT-proBNP tests were coming back within a day,” Dr. Anderson said, “so a really, really good turnaround.”

Individuals were excluded if they had an inpatient admission, echocardiography, or heart failure diagnosis between presentation and the NT-proBNP measurement.

These people were then compared with those presenting to primary or secondary outpatient care for any reason and matched for age, sex, care level, and index year. Both groups were followed up for 1 year.

“Despite this really impressive, almost immediate NT-proBNP testing,” the waiting times to undergo echocardiography were “really disappointing,” Dr. Anderson said.

The median time to first registered echocardiography was 40 days, and only 29% of patients with suspected heart failure received a diagnosis within a year of the index presentation date, which she described as “inadequately slow.”

“And how does this translate to medical therapy?” she asked.
 

Heart Failure Drugs

After the index presentation, the rate of loop diuretic use quadrupled among individuals suspected of having heart failure, but there was a “muted response” when it came to the prescribing of beta-blockers and the other pillars of heart failure therapy, which Dr. Anderson called “very disappointing.”

For outcomes after the index presentation, the rate of hospitalization was much higher in the group with suspected heart failure than in the control group (16.1 vs 2.2 events per 100 person-years). And all-cause mortality occurred more often in the group with suspected heart failure than in the control group (10.3 vs 6.5 events per 100 person-years).

Among patients with NT-proBNP levels of 2000 ng/L, there was a “rapid” onset of hospitalization “within the first few days” of the index presentation, which was tracked by a more linear rise in all-cause deaths, Dr. Anderson reported.

In the United Kingdom, “we are very proud of our 2- and 6-week pathways,” which stipulate that suspected heart failure patients with NT-proBNP levels between 400 and 2000 ng/L are to have a specialist assessment and transthoracic echocardiography within 6 weeks; for those with levels > 2000 ng/L, that interval is accelerated to 2 weeks, she said.

The current results show that “2 weeks is too slow.” And looking at the rest of the cohort with lower NT-proBNP levels, “patients have already been admitted and died” by 6 weeks, she said.

When patients are stratified by age, “you get exactly what you would expect,” Dr. Anderson said. “The older patients are the most at risk” for both hospitalization and all-cause mortality.
 

A version of this article appeared on Medscape.com.

LISBON, PORTUGAL — Few people with suspected heart failure and elevated N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels are receiving a diagnosis after a year, reported investigators, who say high rates of hospitalization are common.

Presenting here at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2024, researchers shared results from the REVOLUTION-HF study involving almost 8000 people who consulted outpatient primary and secondary care over a 5-year period.

About two thirds of the patients had suspected heart failure; however, less than 30% of the people received a diagnosis within a year.

Yet hospitalization was eight times higher in the suspected heart failure group than in the control group, and all-cause mortality was nearly doubled. The outcomes were even worse in patients with high NT-proBNP levels.

Patients with suspected heart failure are “waiting far too long to see a specialist, and that results in a delay to guideline-directed medical therapy, despite the fact that we’re perfectly happy to slap them all on diuretics,” said study presenter Lisa Anderson, MD, PhD, Cardiovascular Clinical Academic Group, Molecular and Clinical Sciences Research Institute, St George’s Hospital, University of London, England.

“We need to rethink our management of heart failure patients presenting in the community,” she said.

A big gap exists internationally between presentation with heart failure, an elevated NT-proBNP, and confirmatory specialist assessment, she explained.

“It’s a scandal that patients are coming to the GP with signs and symptoms of heart failure, they get tested for natriuretic peptides, and nothing happens,” said co-author Antoni Bayés-Genís, MD, PhD, Heart Institute director, Hospital Universitari Germans Trias i Pujol Catedràtic, Barcelona, Spain.

“These patients may receive an echo, or not, in the coming 12 months,” and “during these 12 months, there is a huge number of heart failure hospitalizations and deaths that could probably be prevented.”
 

Why the Reluctance to Diagnose?

Many issues get in the way of early diagnosis, Dr. Bayés-Genís said. “Inertia, comorbidities, ageism.”

A lot of patients with heart failure are elderly women with some degree of weight gain, he said. “And they come to the clinic with fatigue, so we tell them, ‘Well, that’s normal.”

But “it may not be normal,” he added. “This is a very important topic that we, as a society, need to address.”

There are several “misconceptions” about heart failure, said Ileana L. Piña, MD, MPH, the Robert Stein Chair for Quality and Safety, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, who was not involved in the study.

For example, “we’re all convinced that guideline-directed medical therapy works,” but the evidence is only for patients “with a diagnosis.” In addition, “millions of patients get tested” for heart failure, but they already have a “known diagnosis.”

“When we study these drugs, we’re studying them on patients with manifest disease,” who are only then randomized, Dr. Piña said. “But we seldom see them while they’re developing heart failure. And it’s a process; it doesn’t happen overnight.”

Patients initially often think they may have asthma, and so what follows is an extended period of “uncertainty” and “important time lost” before they finally undergo the assessments that show that they have heart failure, she said.

However, “uncertainty” often lands a patient “in the emergency room or with an unscheduled office visit, where NT-proBNP might get ordered and there’s a long lineup for an echo.”

There are several strengths of the current study, Dr. Piña said, including the fact that 50% of the study population were women, and they were older than a typical trial population. Nevertheless, the results were “eye-opening but not surprising” and, in the end, “disappointing.”

“I agree, we need a revolution, Dr. Anderson,” Dr. Piña said. “The revolution of paying attention to the NT-proBNP when you get it and it’s elevated” and then following through with echocardiography and starting “guideline-directed medical therapy early.”

The diagnosis of heart failure “relies on the presentation of patients with nonspecific signs and symptoms,” such as dyspnea and peripheral edema, “but initiation of guideline-directed medical therapy — life-saving treatment — has to wait until we have a formal echocardiography and specialist clinician assessment,” Dr. Anderson said.

The latest clinical consensus statement from the Heart Failure Association “proposes both rule-in and rule-out NT-proBNP levels for heart failure diagnosis, and obviously we all recognize that it’s important to treat patients as soon as they’re diagnosed,” she explained.
 

REVOLUTION-HF

To examine the risk profile for patients presenting to outpatient care with suspected heart failure, the researchers conducted REVOLUTION-HF, which leveraged nationwide Swedish linked data from general practices, specialists, pharmacies, hospitals, and cause of death registers.

“Really impressively, most of these NT-proBNP tests were coming back within a day,” Dr. Anderson said, “so a really, really good turnaround.”

Individuals were excluded if they had an inpatient admission, echocardiography, or heart failure diagnosis between presentation and the NT-proBNP measurement.

These people were then compared with those presenting to primary or secondary outpatient care for any reason and matched for age, sex, care level, and index year. Both groups were followed up for 1 year.

“Despite this really impressive, almost immediate NT-proBNP testing,” the waiting times to undergo echocardiography were “really disappointing,” Dr. Anderson said.

The median time to first registered echocardiography was 40 days, and only 29% of patients with suspected heart failure received a diagnosis within a year of the index presentation date, which she described as “inadequately slow.”

“And how does this translate to medical therapy?” she asked.
 

Heart Failure Drugs

After the index presentation, the rate of loop diuretic use quadrupled among individuals suspected of having heart failure, but there was a “muted response” when it came to the prescribing of beta-blockers and the other pillars of heart failure therapy, which Dr. Anderson called “very disappointing.”

For outcomes after the index presentation, the rate of hospitalization was much higher in the group with suspected heart failure than in the control group (16.1 vs 2.2 events per 100 person-years). And all-cause mortality occurred more often in the group with suspected heart failure than in the control group (10.3 vs 6.5 events per 100 person-years).

Among patients with NT-proBNP levels of 2000 ng/L, there was a “rapid” onset of hospitalization “within the first few days” of the index presentation, which was tracked by a more linear rise in all-cause deaths, Dr. Anderson reported.

In the United Kingdom, “we are very proud of our 2- and 6-week pathways,” which stipulate that suspected heart failure patients with NT-proBNP levels between 400 and 2000 ng/L are to have a specialist assessment and transthoracic echocardiography within 6 weeks; for those with levels > 2000 ng/L, that interval is accelerated to 2 weeks, she said.

The current results show that “2 weeks is too slow.” And looking at the rest of the cohort with lower NT-proBNP levels, “patients have already been admitted and died” by 6 weeks, she said.

When patients are stratified by age, “you get exactly what you would expect,” Dr. Anderson said. “The older patients are the most at risk” for both hospitalization and all-cause mortality.
 

A version of this article appeared on Medscape.com.