Long-term enzyme-inducing drugs for seizures associated with cardiovascular diseases

Treatment with enzyme-inducing anti-epileptic drugs (eiASMs) may be associated with a higher risk of cardiovascular disease (CVD) in adult patients with epilepsy, according to study results published in JAMA Neurology.

Cardiovascular risk factors such as high blood pressure, dyslipidemia, type 2 diabetes, and atrial fibrillation tend to be more common in epilepsy in adulthood. It has been hypothesized that eiASMs used to treat epilepsy may also contribute to the risk of cardiovascular disease. The aim of the current study was to compare the risk associated with eiASMs versus non-eiASMs, examine the risks of eiASM in epileptic incidents, and assess the risk of eiASM in patients diagnosed with epilepsy aged 65 years or older a higher risk of adverse events with long-term use of eiASM.

The study was a review of adult patients from England diagnosed with epilepsy after January 1, 1990 through March 2019. Patients were divided into 3 groups: the total cohort of adults diagnosed with epilepsy after 1990 (n = 31,479), incidents diagnosed after 1998 (n = 7501), and adults who had epilepsy ≥65 years of age Years ago on or after January 1, 1990 (n = 3790). The researchers assessed the incidence of CVD incidents in customized propensity-matched survival analyzes that controlled age, gender, baseline socio-economic status, and cardiovascular risk factors. Weighted cumulative exposure models were also used as part of the analyzes.

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The median age of the patients at diagnosis was 32 years. All patients in the last cohort were free of CVD at the start of the study. Most demographics were similar for patients exposed and not exposed to eiASMs; However, patients who received eiASMs after diagnosis had a longer follow-up period of a median of 2 years (P <0.001).

In the adjusted propensity-matched-Cox proportional hazards model, the hazard ratio (HR) for incidental CVD was higher in patients who received eiASM (HR 1.21; 95% CI 1.06-1.39) . While the absolute difference in the cumulative risk of CVD incidents was slightly higher in the first 8-10 years, the researchers found a sustained divergence of> 1% between 10-25 years of the follow-up period.

In patients with prolonged exposure (> 4 prescriptions), the median HR increased from 1.54 (95% CI, 1.28-1.79) under a relatively defined daily dose of an eiASM of 1 to 2.38 (95% CI, 1st , 52-3.56) with a relative defined daily dose of 2 to 25 years of follow-up compared to patients who did not receive an eiASM. The researchers added that if they limited analyzes to incidents or patients diagnosed when they were> 65 years old, the increased risk was mitigated.

They found that they could not determine whether all patients were adhering to their eiASMs during the study period, which further limited the results.

While short-term use of eiASMs “does not appear to pose a significant risk,” the researchers suggest that “caution should be exercised with long-term use of these drugs.”

Disclosure: Several authors stated links to the pharmaceutical industry. For a full list of the details, see the original article.


Josephson CB, Wiebe S, Delgado-Garcia G, et al. S. JAMA Neurol. Published online October 4, 2021. doi: 10.1001 / jamaneurol.2021.3424

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