Cardiology

Treatment for chronic hypertension in pregnancy with labetalol showed no significant differences in maternal or neonatal outcomes, compared with treatment with nifedipine, new research indicates.

The open-label, multicenter, randomized CHAP (Chronic Hypertension in Pregnancy) trial showed that treating mild chronic hypertension was better than delaying treatment until severe hypertension developed, but still unclear was whether, or to what extent, the choice of first-line treatment affected outcomes.

Researchers, led by Ayodeji A. Sanusi, MD, MPH, with the Division of Maternal and Fetal Medicine at the University of Alabama at Birmingham, conducted a secondary analysis of CHAP to compare the primary treatments. Mild chronic hypertension in the study was defined as blood pressure of 140-159/90-104 mmHg before 20 weeks of gestation.
 

Three Comparisons

Three comparisons were performed in 2292 participants based on medications prescribed at enrollment: 720 (31.4%) received labetalol; 417 (18.2%) initially received nifedipine; and 1155 (50.4%) had standard care. Labetalol was compared with standard care; nifedipine was compared with standard care; and labetalol was compared with nifedipine.

The primary outcome was occurrence of superimposed preeclampsia with severe features; preterm birth before 35 weeks of gestation; placental abruption; or fetal or neonatal death. The key secondary outcome was a small-for-gestational age neonate. Researchers also compared adverse effects between groups.

Among the results were the following:

• The primary outcome occurred in 30.1% in the labetalol group; 31.2% in the nifedipine group; and 37% in the standard care group.
• Risk of the primary outcome was lower among those receiving treatment. For labetalol vs standard care, the adjusted relative risk (RR) was 0.82; 95% confidence interval (CI), 0.72-0.94. For nifedipine vs standard care, the adjusted RR was 0.84; 95% CI, 0.71-0.99. There was no significant difference in risk when labetalol was compared with nifedipine (adjusted RR, 0.98; 95% CI, 0.82-1.18).
• There were no significant differences in numbers of small-for-gestational age neonates or serious adverse events between those who received labetalol and those using nifedipine.

Any adverse events were significantly more common with nifedipine, compared with labetalol (35.7% vs 28.3%, P = .009), and with nifedipine, compared with standard care (35.7% vs 26.3%, P = .0003). Adverse event rates were not significantly higher with labetalol when compared with standard care (28.3% vs 26.3%, P = .34). The most frequently reported adverse events were headache, medication intolerance, dizziness, nausea, dyspepsia, neonatal jaundice, and vomiting.

“Thus, labetalol compared with nifedipine appeared to have fewer adverse events and to be better tolerated,” the authors write. They note that labetalol, a third-generation mixed alpha- and beta-adrenergic antagonist, is contraindicated for those who have obstructive pulmonary disease and nifedipine, a dihydropyridine calcium channel blocker, is contraindicated in people with tachycardia.

The authors write that their results align with other studies that have not found differences between labetalol and nifedipine. “[O]ur findings support the use of either labetalol or nifedipine as initial first-line agents for the management of mild chronic hypertension in pregnancy to reduce the risk of adverse maternal and other perinatal outcomes with no increased risk of fetal harm,” the authors write.

Dr. Sanusi reports no relevant financial relationships. Full coauthor disclosures are available with the full text of the paper.

Treatment for chronic hypertension in pregnancy with labetalol showed no significant differences in maternal or neonatal outcomes, compared with treatment with nifedipine, new research indicates.

The open-label, multicenter, randomized CHAP (Chronic Hypertension in Pregnancy) trial showed that treating mild chronic hypertension was better than delaying treatment until severe hypertension developed, but still unclear was whether, or to what extent, the choice of first-line treatment affected outcomes.

Researchers, led by Ayodeji A. Sanusi, MD, MPH, with the Division of Maternal and Fetal Medicine at the University of Alabama at Birmingham, conducted a secondary analysis of CHAP to compare the primary treatments. Mild chronic hypertension in the study was defined as blood pressure of 140-159/90-104 mmHg before 20 weeks of gestation.
 

Three Comparisons

Three comparisons were performed in 2292 participants based on medications prescribed at enrollment: 720 (31.4%) received labetalol; 417 (18.2%) initially received nifedipine; and 1155 (50.4%) had standard care. Labetalol was compared with standard care; nifedipine was compared with standard care; and labetalol was compared with nifedipine.

The primary outcome was occurrence of superimposed preeclampsia with severe features; preterm birth before 35 weeks of gestation; placental abruption; or fetal or neonatal death. The key secondary outcome was a small-for-gestational age neonate. Researchers also compared adverse effects between groups.

Among the results were the following:

• The primary outcome occurred in 30.1% in the labetalol group; 31.2% in the nifedipine group; and 37% in the standard care group.
• Risk of the primary outcome was lower among those receiving treatment. For labetalol vs standard care, the adjusted relative risk (RR) was 0.82; 95% confidence interval (CI), 0.72-0.94. For nifedipine vs standard care, the adjusted RR was 0.84; 95% CI, 0.71-0.99. There was no significant difference in risk when labetalol was compared with nifedipine (adjusted RR, 0.98; 95% CI, 0.82-1.18).
• There were no significant differences in numbers of small-for-gestational age neonates or serious adverse events between those who received labetalol and those using nifedipine.

Any adverse events were significantly more common with nifedipine, compared with labetalol (35.7% vs 28.3%, P = .009), and with nifedipine, compared with standard care (35.7% vs 26.3%, P = .0003). Adverse event rates were not significantly higher with labetalol when compared with standard care (28.3% vs 26.3%, P = .34). The most frequently reported adverse events were headache, medication intolerance, dizziness, nausea, dyspepsia, neonatal jaundice, and vomiting.

“Thus, labetalol compared with nifedipine appeared to have fewer adverse events and to be better tolerated,” the authors write. They note that labetalol, a third-generation mixed alpha- and beta-adrenergic antagonist, is contraindicated for those who have obstructive pulmonary disease and nifedipine, a dihydropyridine calcium channel blocker, is contraindicated in people with tachycardia.

The authors write that their results align with other studies that have not found differences between labetalol and nifedipine. “[O]ur findings support the use of either labetalol or nifedipine as initial first-line agents for the management of mild chronic hypertension in pregnancy to reduce the risk of adverse maternal and other perinatal outcomes with no increased risk of fetal harm,” the authors write.

Dr. Sanusi reports no relevant financial relationships. Full coauthor disclosures are available with the full text of the paper.

Treatment for chronic hypertension in pregnancy with labetalol showed no significant differences in maternal or neonatal outcomes, compared with treatment with nifedipine, new research indicates.

The open-label, multicenter, randomized CHAP (Chronic Hypertension in Pregnancy) trial showed that treating mild chronic hypertension was better than delaying treatment until severe hypertension developed, but still unclear was whether, or to what extent, the choice of first-line treatment affected outcomes.

Researchers, led by Ayodeji A. Sanusi, MD, MPH, with the Division of Maternal and Fetal Medicine at the University of Alabama at Birmingham, conducted a secondary analysis of CHAP to compare the primary treatments. Mild chronic hypertension in the study was defined as blood pressure of 140-159/90-104 mmHg before 20 weeks of gestation.
 

Three Comparisons

Three comparisons were performed in 2292 participants based on medications prescribed at enrollment: 720 (31.4%) received labetalol; 417 (18.2%) initially received nifedipine; and 1155 (50.4%) had standard care. Labetalol was compared with standard care; nifedipine was compared with standard care; and labetalol was compared with nifedipine.

The primary outcome was occurrence of superimposed preeclampsia with severe features; preterm birth before 35 weeks of gestation; placental abruption; or fetal or neonatal death. The key secondary outcome was a small-for-gestational age neonate. Researchers also compared adverse effects between groups.

Among the results were the following:

• The primary outcome occurred in 30.1% in the labetalol group; 31.2% in the nifedipine group; and 37% in the standard care group.
• Risk of the primary outcome was lower among those receiving treatment. For labetalol vs standard care, the adjusted relative risk (RR) was 0.82; 95% confidence interval (CI), 0.72-0.94. For nifedipine vs standard care, the adjusted RR was 0.84; 95% CI, 0.71-0.99. There was no significant difference in risk when labetalol was compared with nifedipine (adjusted RR, 0.98; 95% CI, 0.82-1.18).
• There were no significant differences in numbers of small-for-gestational age neonates or serious adverse events between those who received labetalol and those using nifedipine.

Any adverse events were significantly more common with nifedipine, compared with labetalol (35.7% vs 28.3%, P = .009), and with nifedipine, compared with standard care (35.7% vs 26.3%, P = .0003). Adverse event rates were not significantly higher with labetalol when compared with standard care (28.3% vs 26.3%, P = .34). The most frequently reported adverse events were headache, medication intolerance, dizziness, nausea, dyspepsia, neonatal jaundice, and vomiting.

“Thus, labetalol compared with nifedipine appeared to have fewer adverse events and to be better tolerated,” the authors write. They note that labetalol, a third-generation mixed alpha- and beta-adrenergic antagonist, is contraindicated for those who have obstructive pulmonary disease and nifedipine, a dihydropyridine calcium channel blocker, is contraindicated in people with tachycardia.

The authors write that their results align with other studies that have not found differences between labetalol and nifedipine. “[O]ur findings support the use of either labetalol or nifedipine as initial first-line agents for the management of mild chronic hypertension in pregnancy to reduce the risk of adverse maternal and other perinatal outcomes with no increased risk of fetal harm,” the authors write.

Dr. Sanusi reports no relevant financial relationships. Full coauthor disclosures are available with the full text of the paper.

SAN DIEGO – Researchers are unraveling the complex relationship between cardiovascular (CV)- and stroke-related outcomes in migraine with, and without, aura.

Early results of one study suggest that aura increases the risk for major adverse cerebrovascular and CV events (MACE) in those with migraine, and that this risk is particularly high in men.

“We confirmed that aura increases the risk for these cerebrovascular and cardiovascular outcomes in people with migraine and that there’s an increased risk of these MACE events in men with migraine,” said study investigator Gina Dumkrieger, PhD, principal data science analyst and assistant professor of neurology, Mayo Clinic, Phoenix, Arizona.

The findings were presented at the annual meeting of the American Headache Society.
 

Few Data on Migraine and Stroke Risk

The extent to which migraine increases the risk for stroke CV outcomes has not been extensively studied.

“We’re trying to find out whether migraine-related factors make it more likely that you’re going to have one of these events,” said Dr. Dumkrieger. “Knowing a particular factor increases the risk is something patients and medical providers would want to know.”

Using Mayo Clinic electronic health records, which cover all three sites (Florida, Minnesota, and Arizona), researchers identified individuals with migraine using diagnostic codes. They also looked at data on sex, race, and the presence of aura.

They investigated whether a history of MACE risk factors — including atrial fibrillation, diabetes, hyperlipidemia, hypertension, and tobacco use — affected risk and the potential interaction of aura with these risk factors.

MACE events included cerebral infarction, intracerebral hemorrhage, and acute myocardial infarction.

The analysis included 130,126 participants (80% women, 95% White individuals). Of these, 6% experienced a MACE event, and 94% did not.

“We confirmed that aura does increase the risk for a MACE event, and all of the known risk factors that we included were also significant,” said Dr. Dumkrieger.

Odds ratios (ORs) were 3.82 for atrial fibrillation, 3.11 for hypertension, and 3.06 for hyperlipidemia.

It was surprising, said Dr. Dumkrieger, that male sex was tied to an increased risk for a MACE event (OR, 1.40). “This is not something that was known before,” she said.

The link between migraine and ischemic stroke, particularly with aura, was stronger in women — particularly young women.

Investigators also found an interaction between male sex and aura, when it comes to MACE outcomes, said Dr. Dumkrieger. “Males in general are at higher risk, and people with aura are at higher risk. Males with aura are also at higher risk, but maybe not as much as you would think they would be. It’s not a purely additive thing. This is something we need to look into more,” she said. 

The study also revealed an interaction between aura and hypertension as well as aura and tobacco use, but here too, it was not an additive risk, said Dr. Dumkrieger. However, she added, the presence of aura does not moderate the risk for hyperlipidemia, diabetes, or atrial fibrillation.

The research also showed a significant interaction between male sex and Black race which was additive. “There’s apparently increased risk if you are male and Black or African American that’s greater than what you would expect. We should be especially concerned about these individuals,” she said.
 

Unanswered Questions

The current analysis is part of a larger study that will more closely examine these relationships. “We want to learn, for example, why aura moderates some of the risk factors but not others,” said Dr. Dumkrieger.

The researchers also plan to investigate other migraine features, including headache frequency, and headache sensations such as pulsating or throbbing.

Dr. Dumkrieger was an investigator of another study, also presented at the AHS meeting, that’s investigating the role of migraine-specific features and imaging results in the complex interrelationship between migraine and MACE risk.

That study, which also used the Mayo Clinic electronic health record data, included 60,454 migraine patients diagnosed with migraine after 2010.

Researchers divided participants into those with a MACE outcome (1107) and those without such an outcome (59,347) after at least 2 years of follow-up. They created a propensity cohort of individuals matched for age and risk factors for MACE outcome.

The final cohort consisted of 575 patients with and 652 patients without MACE outcome.

One of the most interesting early results from this study was that those with a MACE outcome had significantly more white matter hyperintensities than those with no MACE outcome, at 64% versus 51%, respectively. 

This and other findings need to be validated in a different cohort with an electronic health records database from another institution. In future, the team plans to focus on identifying specific migraine features and medications and their relative contributions to MACE risk in migraine patients.

Yet another study featured at the AHS meeting confirmed the increased risk for stroke among migraine patients using a large database with over 410,000 subjects.

Results showed stroke was more than three times more common in those with a migraine diagnosis than in those without (risk ratio, [RR] 3.23; P < .001). The RR for hemorrhagic stroke (3.15) was comparable with that of ischemic stroke (3.20).

The overall stroke RR for chronic migraine versus controls without migraine was 3.68 (P < .001). The RR for migraine with aura versus migraine without aura was 1.37 (P < .001).
 

Useful Data

Commenting on the research, Juliana VanderPluym, MD, a headache specialist at the Mayo Clinic, Phoenix, Arizona, described this new information as “very useful.”

The fact that there are more white matter lesions on MRI scans in migraine patients with MACE needs further exploration, said Dr. VanderPluym.

“Understanding how much of that relates to migraine, how much relates to other comorbid conditions, and what this all means together, is very important, particularly because MACE can be life-threatening and life-altering,” she added.

Learning how migraine medications may impact MACE risk is also something that needs to be examined in greater depth, she said. “I would think that migraines that are controlled might have a different risk for MACE than uncontrolled migraine,” she said.

The investigators reported no relevant financial conflicts of interest.

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

SAN DIEGO – Researchers are unraveling the complex relationship between cardiovascular (CV)- and stroke-related outcomes in migraine with, and without, aura.

Early results of one study suggest that aura increases the risk for major adverse cerebrovascular and CV events (MACE) in those with migraine, and that this risk is particularly high in men.

“We confirmed that aura increases the risk for these cerebrovascular and cardiovascular outcomes in people with migraine and that there’s an increased risk of these MACE events in men with migraine,” said study investigator Gina Dumkrieger, PhD, principal data science analyst and assistant professor of neurology, Mayo Clinic, Phoenix, Arizona.

The findings were presented at the annual meeting of the American Headache Society.
 

Few Data on Migraine and Stroke Risk

The extent to which migraine increases the risk for stroke CV outcomes has not been extensively studied.

“We’re trying to find out whether migraine-related factors make it more likely that you’re going to have one of these events,” said Dr. Dumkrieger. “Knowing a particular factor increases the risk is something patients and medical providers would want to know.”

Using Mayo Clinic electronic health records, which cover all three sites (Florida, Minnesota, and Arizona), researchers identified individuals with migraine using diagnostic codes. They also looked at data on sex, race, and the presence of aura.

They investigated whether a history of MACE risk factors — including atrial fibrillation, diabetes, hyperlipidemia, hypertension, and tobacco use — affected risk and the potential interaction of aura with these risk factors.

MACE events included cerebral infarction, intracerebral hemorrhage, and acute myocardial infarction.

The analysis included 130,126 participants (80% women, 95% White individuals). Of these, 6% experienced a MACE event, and 94% did not.

“We confirmed that aura does increase the risk for a MACE event, and all of the known risk factors that we included were also significant,” said Dr. Dumkrieger.

Odds ratios (ORs) were 3.82 for atrial fibrillation, 3.11 for hypertension, and 3.06 for hyperlipidemia.

It was surprising, said Dr. Dumkrieger, that male sex was tied to an increased risk for a MACE event (OR, 1.40). “This is not something that was known before,” she said.

The link between migraine and ischemic stroke, particularly with aura, was stronger in women — particularly young women.

Investigators also found an interaction between male sex and aura, when it comes to MACE outcomes, said Dr. Dumkrieger. “Males in general are at higher risk, and people with aura are at higher risk. Males with aura are also at higher risk, but maybe not as much as you would think they would be. It’s not a purely additive thing. This is something we need to look into more,” she said. 

The study also revealed an interaction between aura and hypertension as well as aura and tobacco use, but here too, it was not an additive risk, said Dr. Dumkrieger. However, she added, the presence of aura does not moderate the risk for hyperlipidemia, diabetes, or atrial fibrillation.

The research also showed a significant interaction between male sex and Black race which was additive. “There’s apparently increased risk if you are male and Black or African American that’s greater than what you would expect. We should be especially concerned about these individuals,” she said.
 

Unanswered Questions

The current analysis is part of a larger study that will more closely examine these relationships. “We want to learn, for example, why aura moderates some of the risk factors but not others,” said Dr. Dumkrieger.

The researchers also plan to investigate other migraine features, including headache frequency, and headache sensations such as pulsating or throbbing.

Dr. Dumkrieger was an investigator of another study, also presented at the AHS meeting, that’s investigating the role of migraine-specific features and imaging results in the complex interrelationship between migraine and MACE risk.

That study, which also used the Mayo Clinic electronic health record data, included 60,454 migraine patients diagnosed with migraine after 2010.

Researchers divided participants into those with a MACE outcome (1107) and those without such an outcome (59,347) after at least 2 years of follow-up. They created a propensity cohort of individuals matched for age and risk factors for MACE outcome.

The final cohort consisted of 575 patients with and 652 patients without MACE outcome.

One of the most interesting early results from this study was that those with a MACE outcome had significantly more white matter hyperintensities than those with no MACE outcome, at 64% versus 51%, respectively. 

This and other findings need to be validated in a different cohort with an electronic health records database from another institution. In future, the team plans to focus on identifying specific migraine features and medications and their relative contributions to MACE risk in migraine patients.

Yet another study featured at the AHS meeting confirmed the increased risk for stroke among migraine patients using a large database with over 410,000 subjects.

Results showed stroke was more than three times more common in those with a migraine diagnosis than in those without (risk ratio, [RR] 3.23; P < .001). The RR for hemorrhagic stroke (3.15) was comparable with that of ischemic stroke (3.20).

The overall stroke RR for chronic migraine versus controls without migraine was 3.68 (P < .001). The RR for migraine with aura versus migraine without aura was 1.37 (P < .001).
 

Useful Data

Commenting on the research, Juliana VanderPluym, MD, a headache specialist at the Mayo Clinic, Phoenix, Arizona, described this new information as “very useful.”

The fact that there are more white matter lesions on MRI scans in migraine patients with MACE needs further exploration, said Dr. VanderPluym.

“Understanding how much of that relates to migraine, how much relates to other comorbid conditions, and what this all means together, is very important, particularly because MACE can be life-threatening and life-altering,” she added.

Learning how migraine medications may impact MACE risk is also something that needs to be examined in greater depth, she said. “I would think that migraines that are controlled might have a different risk for MACE than uncontrolled migraine,” she said.

The investigators reported no relevant financial conflicts of interest.

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

SAN DIEGO – Researchers are unraveling the complex relationship between cardiovascular (CV)- and stroke-related outcomes in migraine with, and without, aura.

Early results of one study suggest that aura increases the risk for major adverse cerebrovascular and CV events (MACE) in those with migraine, and that this risk is particularly high in men.

“We confirmed that aura increases the risk for these cerebrovascular and cardiovascular outcomes in people with migraine and that there’s an increased risk of these MACE events in men with migraine,” said study investigator Gina Dumkrieger, PhD, principal data science analyst and assistant professor of neurology, Mayo Clinic, Phoenix, Arizona.

The findings were presented at the annual meeting of the American Headache Society.
 

Few Data on Migraine and Stroke Risk

The extent to which migraine increases the risk for stroke CV outcomes has not been extensively studied.

“We’re trying to find out whether migraine-related factors make it more likely that you’re going to have one of these events,” said Dr. Dumkrieger. “Knowing a particular factor increases the risk is something patients and medical providers would want to know.”

Using Mayo Clinic electronic health records, which cover all three sites (Florida, Minnesota, and Arizona), researchers identified individuals with migraine using diagnostic codes. They also looked at data on sex, race, and the presence of aura.

They investigated whether a history of MACE risk factors — including atrial fibrillation, diabetes, hyperlipidemia, hypertension, and tobacco use — affected risk and the potential interaction of aura with these risk factors.

MACE events included cerebral infarction, intracerebral hemorrhage, and acute myocardial infarction.

The analysis included 130,126 participants (80% women, 95% White individuals). Of these, 6% experienced a MACE event, and 94% did not.

“We confirmed that aura does increase the risk for a MACE event, and all of the known risk factors that we included were also significant,” said Dr. Dumkrieger.

Odds ratios (ORs) were 3.82 for atrial fibrillation, 3.11 for hypertension, and 3.06 for hyperlipidemia.

It was surprising, said Dr. Dumkrieger, that male sex was tied to an increased risk for a MACE event (OR, 1.40). “This is not something that was known before,” she said.

The link between migraine and ischemic stroke, particularly with aura, was stronger in women — particularly young women.

Investigators also found an interaction between male sex and aura, when it comes to MACE outcomes, said Dr. Dumkrieger. “Males in general are at higher risk, and people with aura are at higher risk. Males with aura are also at higher risk, but maybe not as much as you would think they would be. It’s not a purely additive thing. This is something we need to look into more,” she said. 

The study also revealed an interaction between aura and hypertension as well as aura and tobacco use, but here too, it was not an additive risk, said Dr. Dumkrieger. However, she added, the presence of aura does not moderate the risk for hyperlipidemia, diabetes, or atrial fibrillation.

The research also showed a significant interaction between male sex and Black race which was additive. “There’s apparently increased risk if you are male and Black or African American that’s greater than what you would expect. We should be especially concerned about these individuals,” she said.
 

Unanswered Questions

The current analysis is part of a larger study that will more closely examine these relationships. “We want to learn, for example, why aura moderates some of the risk factors but not others,” said Dr. Dumkrieger.

The researchers also plan to investigate other migraine features, including headache frequency, and headache sensations such as pulsating or throbbing.

Dr. Dumkrieger was an investigator of another study, also presented at the AHS meeting, that’s investigating the role of migraine-specific features and imaging results in the complex interrelationship between migraine and MACE risk.

That study, which also used the Mayo Clinic electronic health record data, included 60,454 migraine patients diagnosed with migraine after 2010.

Researchers divided participants into those with a MACE outcome (1107) and those without such an outcome (59,347) after at least 2 years of follow-up. They created a propensity cohort of individuals matched for age and risk factors for MACE outcome.

The final cohort consisted of 575 patients with and 652 patients without MACE outcome.

One of the most interesting early results from this study was that those with a MACE outcome had significantly more white matter hyperintensities than those with no MACE outcome, at 64% versus 51%, respectively. 

This and other findings need to be validated in a different cohort with an electronic health records database from another institution. In future, the team plans to focus on identifying specific migraine features and medications and their relative contributions to MACE risk in migraine patients.

Yet another study featured at the AHS meeting confirmed the increased risk for stroke among migraine patients using a large database with over 410,000 subjects.

Results showed stroke was more than three times more common in those with a migraine diagnosis than in those without (risk ratio, [RR] 3.23; P < .001). The RR for hemorrhagic stroke (3.15) was comparable with that of ischemic stroke (3.20).

The overall stroke RR for chronic migraine versus controls without migraine was 3.68 (P < .001). The RR for migraine with aura versus migraine without aura was 1.37 (P < .001).
 

Useful Data

Commenting on the research, Juliana VanderPluym, MD, a headache specialist at the Mayo Clinic, Phoenix, Arizona, described this new information as “very useful.”

The fact that there are more white matter lesions on MRI scans in migraine patients with MACE needs further exploration, said Dr. VanderPluym.

“Understanding how much of that relates to migraine, how much relates to other comorbid conditions, and what this all means together, is very important, particularly because MACE can be life-threatening and life-altering,” she added.

Learning how migraine medications may impact MACE risk is also something that needs to be examined in greater depth, she said. “I would think that migraines that are controlled might have a different risk for MACE than uncontrolled migraine,” she said.

The investigators reported no relevant financial conflicts of interest.

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

LYON, France – Lerodalcibep, a novel, third-generation anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, helps high-risk patients already receiving maximally tolerated statins to achieve guideline lipid targets, reported investigators.

In the randomized, placebo-controlled LIBerate-CVD trial of more than 900 patients, lerodalcibep led to reductions from baseline in low-density lipoprotein (LDL) cholesterol levels of more than 60%.

“We believe that lerodalcibep offers a novel, effective alternative to current PCSK9 inhibitors for patients with cardiovascular disease or at very high risk for cardiovascular disease,” said Evan Stein, MD, PhD, chief scientific officer and cofounder of LIB Therapeutics in Chicago, who presented the findings at the European Atherosclerosis Society (EAS) 2024.

Moreover, it leads to “substantial additional LDL cholesterol reductions on top of existing oral agents” and allows more than 90% of patients to achieve the latest European Society of Cardiology (ESC) guideline targets, he said.

Lerodalcibep has “tolerability and safety similar to placebo,” Dr. Stein said, and requires only “a small monthly injection, which takes about 12 seconds.”

“The drug doesn’t require refrigeration” and is “stable, so far, over 9 months,” he reported.

The latest data “confirm the efficacy of lerodalcibep,” said Giuseppe Danilo Norata, PhD, from the Department of Pharmacological and Biomolecular Sciences at the University of Milan, Milan, Italy, who was not involved in the study.

The LDL cholesterol reduction in this phase 3 trial is “in line with what was observed in LIBerate-FH,” and the high proportion of patients achieving their LDL cholesterol target is “impressive,” he added.
 

Effective and Well Tolerated

The safety results are “suggestive of a drug that is well tolerated, with injection-site reactions being the only remarkable adverse event increased in the treatment group,” Dr. Norata reported.

Only a “limited number” of patients developed neutralizing antidrug antibodies, which did not affect the efficacy of lerodalcibep. However, “given that the therapy is expected to be administered for years,” a longer analysis is needed to exclude the concern that a small percentage of neutralizing antidrug antibodies could reduce the efficacy, he said.

If approved, lerodalcibep could end up as a first-line option in the treatment pathway for high-risk cardiovascular disease because the efficacy “is similar to that of other injectable PCSK9 inhibitors,” he said, adding that its position in the market will “largely depend on the price.”

As the mechanism of action is similar to that of other monoclonal antibodies, “there is no pharmacological rationale to use it after another PSCK9 inhibitor,” he explained.

Lerodalcibep is a small recombinant fusion protein that combines a PCSK9-binding domain with human serum albumin.

The binding domain blocks the interaction between PCSK9 and the LDL cholesterol receptor, and the albumin linkage increases the half-life to 12-15 days, allowing low-volume injections to be given every 4 weeks.

A prior phase 2 study suggested that lerodalcibep substantially decreases LDL cholesterol levels in patients already taking maximally tolerated statins. The 300-mg dose was associated with an average reduction from baseline in LDL cholesterol levels of 77% over 12 weeks, whereas free PCSK9 levels decreased by 88%.

The current phase 3 study enrolled individuals at 65 centers in 100 countries who had or were at a very high risk for cardiovascular disease and who had an LDL cholesterol level of ≥ 1.8 mmol/L despite being on maximally tolerated statins.

Study participants were randomized in a 2:1 ratio to receive monthly subcutaneous lerodalcibep (n = 614) or placebo (n = 308) for 52 weeks and were assessed for the co-primary endpoints of the percentage change in LDL cholesterol levels from baseline to week 52 and the mean of levels at weeks 50 and 52.

The mean age was similar in the lerodalcibep and placebo groups (63.3 vs 64.5 years), as were the proportion of female (30% vs 30%) and White (80% vs 79%) participants.

The vast majority of participants in the lerodalcibep and placebo groups had a documented cardiovascular event (85.3% vs 86.4%) and were receiving secondary prevention, and 87% and 82%, respectively, were receiving a statin (any dose).

In a modified intention-to-treat analysis, the mean placebo-adjusted reduction in LDL cholesterol levels from baseline with lerodalcibep was 62% at week 52 (P < .0001), and the mean of levels at weeks 50 and 52 was 69.4% (P < .0001).

Similar results were seen in a per protocol analysis and an intention-to-treat analysis with imputation, which is a US Food and Drug Administration measure introduced in 2021 that assumes patients who discontinue the study treatment have an outcome similar to that in the placebo patients.

Moreover, 98.2% of patients in the lerodalcibep group achieved the ESC and European Atherosclerosis Society recommended reduction in LDL cholesterol levels of ≥ 50%, whereas only 8.8% in the placebo group did.
 

Hitting the LDL Cholesterol Target

More patients in the lerodalcibep group than in the placebo group achieved the LDL cholesterol target of < 1.4 mmol/L (95.3% vs 18.5%), and more patients in the lerodalcibep group achieved both that target and the ≥ 50% target (94.5% and 6.8%).

Lerodalcibep was also associated with significant reductions from baseline in levels of non–high-density lipoprotein (HDL) cholesterol, apolipoprotein B, very LDL cholesterol, and triglycerides, as well as an increase in HDL cholesterol levels (P < .0001 for all).

In terms of safety, lerodalcibep was associated with an adverse event rate leading to withdrawal similar to that seen with placebo (4.2% vs 3.6%), and 15.9% and 14.8% of patients, respectively, experienced at least one serious adverse event.

In-stent restenosis occurred more often in the lerodalcibep group than in the placebo group (5.4% vs 2.0%).

The study drug was associated with low levels of transient and sporadic antidrug antibodies and a low rate of neutralizing antidrug antibodies (0.9%), which were not associated with restenosis, a reduction in free PCSK9 levels, or the ability of lerodalcibep to lower LDL cholesterol levels.

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

LYON, France – Lerodalcibep, a novel, third-generation anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, helps high-risk patients already receiving maximally tolerated statins to achieve guideline lipid targets, reported investigators.

In the randomized, placebo-controlled LIBerate-CVD trial of more than 900 patients, lerodalcibep led to reductions from baseline in low-density lipoprotein (LDL) cholesterol levels of more than 60%.

“We believe that lerodalcibep offers a novel, effective alternative to current PCSK9 inhibitors for patients with cardiovascular disease or at very high risk for cardiovascular disease,” said Evan Stein, MD, PhD, chief scientific officer and cofounder of LIB Therapeutics in Chicago, who presented the findings at the European Atherosclerosis Society (EAS) 2024.

Moreover, it leads to “substantial additional LDL cholesterol reductions on top of existing oral agents” and allows more than 90% of patients to achieve the latest European Society of Cardiology (ESC) guideline targets, he said.

Lerodalcibep has “tolerability and safety similar to placebo,” Dr. Stein said, and requires only “a small monthly injection, which takes about 12 seconds.”

“The drug doesn’t require refrigeration” and is “stable, so far, over 9 months,” he reported.

The latest data “confirm the efficacy of lerodalcibep,” said Giuseppe Danilo Norata, PhD, from the Department of Pharmacological and Biomolecular Sciences at the University of Milan, Milan, Italy, who was not involved in the study.

The LDL cholesterol reduction in this phase 3 trial is “in line with what was observed in LIBerate-FH,” and the high proportion of patients achieving their LDL cholesterol target is “impressive,” he added.
 

Effective and Well Tolerated

The safety results are “suggestive of a drug that is well tolerated, with injection-site reactions being the only remarkable adverse event increased in the treatment group,” Dr. Norata reported.

Only a “limited number” of patients developed neutralizing antidrug antibodies, which did not affect the efficacy of lerodalcibep. However, “given that the therapy is expected to be administered for years,” a longer analysis is needed to exclude the concern that a small percentage of neutralizing antidrug antibodies could reduce the efficacy, he said.

If approved, lerodalcibep could end up as a first-line option in the treatment pathway for high-risk cardiovascular disease because the efficacy “is similar to that of other injectable PCSK9 inhibitors,” he said, adding that its position in the market will “largely depend on the price.”

As the mechanism of action is similar to that of other monoclonal antibodies, “there is no pharmacological rationale to use it after another PSCK9 inhibitor,” he explained.

Lerodalcibep is a small recombinant fusion protein that combines a PCSK9-binding domain with human serum albumin.

The binding domain blocks the interaction between PCSK9 and the LDL cholesterol receptor, and the albumin linkage increases the half-life to 12-15 days, allowing low-volume injections to be given every 4 weeks.

A prior phase 2 study suggested that lerodalcibep substantially decreases LDL cholesterol levels in patients already taking maximally tolerated statins. The 300-mg dose was associated with an average reduction from baseline in LDL cholesterol levels of 77% over 12 weeks, whereas free PCSK9 levels decreased by 88%.

The current phase 3 study enrolled individuals at 65 centers in 100 countries who had or were at a very high risk for cardiovascular disease and who had an LDL cholesterol level of ≥ 1.8 mmol/L despite being on maximally tolerated statins.

Study participants were randomized in a 2:1 ratio to receive monthly subcutaneous lerodalcibep (n = 614) or placebo (n = 308) for 52 weeks and were assessed for the co-primary endpoints of the percentage change in LDL cholesterol levels from baseline to week 52 and the mean of levels at weeks 50 and 52.

The mean age was similar in the lerodalcibep and placebo groups (63.3 vs 64.5 years), as were the proportion of female (30% vs 30%) and White (80% vs 79%) participants.

The vast majority of participants in the lerodalcibep and placebo groups had a documented cardiovascular event (85.3% vs 86.4%) and were receiving secondary prevention, and 87% and 82%, respectively, were receiving a statin (any dose).

In a modified intention-to-treat analysis, the mean placebo-adjusted reduction in LDL cholesterol levels from baseline with lerodalcibep was 62% at week 52 (P < .0001), and the mean of levels at weeks 50 and 52 was 69.4% (P < .0001).

Similar results were seen in a per protocol analysis and an intention-to-treat analysis with imputation, which is a US Food and Drug Administration measure introduced in 2021 that assumes patients who discontinue the study treatment have an outcome similar to that in the placebo patients.

Moreover, 98.2% of patients in the lerodalcibep group achieved the ESC and European Atherosclerosis Society recommended reduction in LDL cholesterol levels of ≥ 50%, whereas only 8.8% in the placebo group did.
 

Hitting the LDL Cholesterol Target

More patients in the lerodalcibep group than in the placebo group achieved the LDL cholesterol target of < 1.4 mmol/L (95.3% vs 18.5%), and more patients in the lerodalcibep group achieved both that target and the ≥ 50% target (94.5% and 6.8%).

Lerodalcibep was also associated with significant reductions from baseline in levels of non–high-density lipoprotein (HDL) cholesterol, apolipoprotein B, very LDL cholesterol, and triglycerides, as well as an increase in HDL cholesterol levels (P < .0001 for all).

In terms of safety, lerodalcibep was associated with an adverse event rate leading to withdrawal similar to that seen with placebo (4.2% vs 3.6%), and 15.9% and 14.8% of patients, respectively, experienced at least one serious adverse event.

In-stent restenosis occurred more often in the lerodalcibep group than in the placebo group (5.4% vs 2.0%).

The study drug was associated with low levels of transient and sporadic antidrug antibodies and a low rate of neutralizing antidrug antibodies (0.9%), which were not associated with restenosis, a reduction in free PCSK9 levels, or the ability of lerodalcibep to lower LDL cholesterol levels.

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

LYON, France – Lerodalcibep, a novel, third-generation anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, helps high-risk patients already receiving maximally tolerated statins to achieve guideline lipid targets, reported investigators.

In the randomized, placebo-controlled LIBerate-CVD trial of more than 900 patients, lerodalcibep led to reductions from baseline in low-density lipoprotein (LDL) cholesterol levels of more than 60%.

“We believe that lerodalcibep offers a novel, effective alternative to current PCSK9 inhibitors for patients with cardiovascular disease or at very high risk for cardiovascular disease,” said Evan Stein, MD, PhD, chief scientific officer and cofounder of LIB Therapeutics in Chicago, who presented the findings at the European Atherosclerosis Society (EAS) 2024.

Moreover, it leads to “substantial additional LDL cholesterol reductions on top of existing oral agents” and allows more than 90% of patients to achieve the latest European Society of Cardiology (ESC) guideline targets, he said.

Lerodalcibep has “tolerability and safety similar to placebo,” Dr. Stein said, and requires only “a small monthly injection, which takes about 12 seconds.”

“The drug doesn’t require refrigeration” and is “stable, so far, over 9 months,” he reported.

The latest data “confirm the efficacy of lerodalcibep,” said Giuseppe Danilo Norata, PhD, from the Department of Pharmacological and Biomolecular Sciences at the University of Milan, Milan, Italy, who was not involved in the study.

The LDL cholesterol reduction in this phase 3 trial is “in line with what was observed in LIBerate-FH,” and the high proportion of patients achieving their LDL cholesterol target is “impressive,” he added.
 

Effective and Well Tolerated

The safety results are “suggestive of a drug that is well tolerated, with injection-site reactions being the only remarkable adverse event increased in the treatment group,” Dr. Norata reported.

Only a “limited number” of patients developed neutralizing antidrug antibodies, which did not affect the efficacy of lerodalcibep. However, “given that the therapy is expected to be administered for years,” a longer analysis is needed to exclude the concern that a small percentage of neutralizing antidrug antibodies could reduce the efficacy, he said.

If approved, lerodalcibep could end up as a first-line option in the treatment pathway for high-risk cardiovascular disease because the efficacy “is similar to that of other injectable PCSK9 inhibitors,” he said, adding that its position in the market will “largely depend on the price.”

As the mechanism of action is similar to that of other monoclonal antibodies, “there is no pharmacological rationale to use it after another PSCK9 inhibitor,” he explained.

Lerodalcibep is a small recombinant fusion protein that combines a PCSK9-binding domain with human serum albumin.

The binding domain blocks the interaction between PCSK9 and the LDL cholesterol receptor, and the albumin linkage increases the half-life to 12-15 days, allowing low-volume injections to be given every 4 weeks.

A prior phase 2 study suggested that lerodalcibep substantially decreases LDL cholesterol levels in patients already taking maximally tolerated statins. The 300-mg dose was associated with an average reduction from baseline in LDL cholesterol levels of 77% over 12 weeks, whereas free PCSK9 levels decreased by 88%.

The current phase 3 study enrolled individuals at 65 centers in 100 countries who had or were at a very high risk for cardiovascular disease and who had an LDL cholesterol level of ≥ 1.8 mmol/L despite being on maximally tolerated statins.

Study participants were randomized in a 2:1 ratio to receive monthly subcutaneous lerodalcibep (n = 614) or placebo (n = 308) for 52 weeks and were assessed for the co-primary endpoints of the percentage change in LDL cholesterol levels from baseline to week 52 and the mean of levels at weeks 50 and 52.

The mean age was similar in the lerodalcibep and placebo groups (63.3 vs 64.5 years), as were the proportion of female (30% vs 30%) and White (80% vs 79%) participants.

The vast majority of participants in the lerodalcibep and placebo groups had a documented cardiovascular event (85.3% vs 86.4%) and were receiving secondary prevention, and 87% and 82%, respectively, were receiving a statin (any dose).

In a modified intention-to-treat analysis, the mean placebo-adjusted reduction in LDL cholesterol levels from baseline with lerodalcibep was 62% at week 52 (P < .0001), and the mean of levels at weeks 50 and 52 was 69.4% (P < .0001).

Similar results were seen in a per protocol analysis and an intention-to-treat analysis with imputation, which is a US Food and Drug Administration measure introduced in 2021 that assumes patients who discontinue the study treatment have an outcome similar to that in the placebo patients.

Moreover, 98.2% of patients in the lerodalcibep group achieved the ESC and European Atherosclerosis Society recommended reduction in LDL cholesterol levels of ≥ 50%, whereas only 8.8% in the placebo group did.
 

Hitting the LDL Cholesterol Target

More patients in the lerodalcibep group than in the placebo group achieved the LDL cholesterol target of < 1.4 mmol/L (95.3% vs 18.5%), and more patients in the lerodalcibep group achieved both that target and the ≥ 50% target (94.5% and 6.8%).

Lerodalcibep was also associated with significant reductions from baseline in levels of non–high-density lipoprotein (HDL) cholesterol, apolipoprotein B, very LDL cholesterol, and triglycerides, as well as an increase in HDL cholesterol levels (P < .0001 for all).

In terms of safety, lerodalcibep was associated with an adverse event rate leading to withdrawal similar to that seen with placebo (4.2% vs 3.6%), and 15.9% and 14.8% of patients, respectively, experienced at least one serious adverse event.

In-stent restenosis occurred more often in the lerodalcibep group than in the placebo group (5.4% vs 2.0%).

The study drug was associated with low levels of transient and sporadic antidrug antibodies and a low rate of neutralizing antidrug antibodies (0.9%), which were not associated with restenosis, a reduction in free PCSK9 levels, or the ability of lerodalcibep to lower LDL cholesterol levels.

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.

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.

Bunick_Christopher_CONN_web.jpg

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.”

[embed:render:related:node:267679]

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.

Bunick_Christopher_CONN_web.jpg

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.”

[embed:render:related:node:267679]

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.

Bunick_Christopher_CONN_web.jpg

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.”

[embed:render:related:node:267679]

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.