Some Epilepsy Drugs Tied to Cardiovascular Events in Older People

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 The latest here:

Some Epilepsy Drugs Tied to Cardiovascular Events in Older People

Link likely due to enzyme-inducing antiseizure medications

by Sophie Putka, Enterprise & Investigative Writer, MedPage Today October 2, 2024

An association between epilepsy and cardiovascular events (CVEs) in older people was likely largely due to the use of enzyme-inducing antiseizure medications (EIASM), according to a prospective cohort study from Canada.

Among over 27,000 participants, new-onset CVEs were more likely in those with epilepsy than those without (adjusted OR 2.20, 95% CI 1.48-3.27), with the relative contribution to this association highest for "strong" EIASM use (24.6%), reported Mark Keezer, MD, PhD, of Centre de Recherche du Centre Hospitalier de l'Université de Montréal, and colleagues in JAMA Neurology.

"Our study suggests that enzyme-inducing antiseizure medications increase the risk of cardiovascular events," Keezer told MedPage Today. "Future studies will need to study whether this should lead to screening for cardiovascular disease in certain people at greater risk. Our study may also provide healthcare professionals further justification for avoiding enzyme-inducing antiseizure medications, when clinically feasible."

There is a strong association between epilepsy and cardiovascular disease, at least partly because of the overlap in risk factors, Keezer and co-authors noted. Stroke can cause epilepsy, and even in populations without cerebrovascular disease, the risk of developing cardiovascular disease is high, they pointed out. Previous research has suggested that potential damage to the heart and coronary vasculature by repeat seizures may contribute to this connection, along with EIASM use.

For this study, Keezer and team used data from 27,230 participants in the ongoing Canadian Longitudinal Study on Aging (CLSA) with 6 years of follow-up from 2015 to 2021. The CLSA includes adults ages 45 to 85 and excludes residents of long-term care facilities and those with cognitive impairment, among others.

Participants were included in this analysis if they reported no previous history of CVEs (stroke, transient ischemic attack, or myocardial infarction) at baseline. Mean age was 62.3, 52.4% were women, and 94.4% were white. In total, 431 had a lifetime history of epilepsy. Of those included, 86% completed follow-up.

The primary outcome was new-onset CVEs over 6 years, and new-onset strokes, transient ischemic attacks, or myocardial infarctions separately were secondary outcomes. To understand how mediator variables influenced relationships between epilepsy and CVEs, the researchers ran mediation analyses for strong EIASM use, weak EIASM use, Framingham score, Physical Activity Scale for the Elderly (PASE) score, and waist-to-hip ratio.

"Strong EIASM use" included use of carbamazepine, phenytoin, phenobarbital, and primidone, while "weak EIASM use" included use of drugs like oxcarbazepine, eslicarbazepine, topiramate, and rufinamide. Of the CVEs, strong EIASM use appeared to have the largest effect on myocardial infarction, with a proportion-mediated value of 59.1%.

Apart from the mediating effect of strong EIASM use, "more than two-thirds of this association may be due to other factors, such as more prevalent [cardiovascular risk factors] or a direct effect of epilepsy on [cardiovascular disease]," Keezer and colleagues wrote. Weak EIASM use, PASE score, and waist-to-hip ratio also played a role, with proportion-mediated values of 4.0%, 3.3%, and 1.6%, respectively.

The authors noted that they were limited by self-reported data, and by potential effects of the 14% of participants lost to follow-up. They also did not differentiate between ischemic stroke and hemorrhagic stroke, and noted that participants may have begun or stopped EIASM during follow-up, but EIASM data were only available for baseline use.

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  Sophie Putka is an enterprise and investigative writer for MedPage Today. Her work has appeared in the Wall Street Journal, Discover, Business Insider, Inverse, Cannabis Wire, and more. She joined MedPage Today in August of 2021. Follow

Disclosures

Data/biospecimens for this study came from the Canadian Longitudinal Study on Aging, which is funded by the Government of Canada through the Canadian Institutes of Health Research and the Canada Foundation for Innovation.

Keezer reported financial relationships with UCB, Eisai, Jazz Pharmaceuticals, and Paladin.

Co-authors reported financial relationships with Fonds de Recherche du Québec-Santé Support, Xenon, Theravance, Novartis, Eisai, Angelini Pharma, LivAssured, UCB, Montreal Heart Institute, and Jazz Pharmaceuticals.

Primary Source

JAMA Neurology

Source Reference: Li J, et al "Antiseizure medications and cardiovascular events in older people with epilepsy" JAMA Neurol 2024; DOI: 10.1001/jamaneurol.2024.3210.