Angiotensin Receptor Blockers Linked to Reduced Risk of New-Onset Epilepsy in Hypertensive Patients: Study

The findings, published in JAMA Neurology, suggest that ARBs were associated with a lower incidence of new-onset epilepsy than other antihypertensive agents in patients with hypertension.

Human and animal studies have suggested that the use of angiotensin receptor blockers may be associated with a lower risk of incident epilepsy compared with other antihypertensive medications. However, there is a lack of observational data from the US. To fill this knowledge gap, Xuerong Wen, Department of Pharmacy Practice and Clinical Research, College of Pharmacy, University of Rhode Island, Kingston, and colleagues aimed to evaluate the association between ARB use and epilepsy incidence in subgroups of US patients with hypertension.

For this purpose, the researchers conducted a retrospective cohort study using data from a national health administrative database from 2010 to 2017, with propensity score (PS) matching. The eligible cohort included privately insured individuals aged 18 years or older with primary hypertension diagnosis and dispensed at least one ARB, β-blocker, calcium channel blocker (CCB), or angiotensin-converting enzyme inhibitor (ACEI).

It excluded patients with epilepsy diagnosis at or before the index date or dispensed an antiseizure medication 12 months before or 90 days after initiating the study medications. Based on baseline covariates, propensity scores were generated and used to match patients who received ARBs with those who received either β-blockers, ACEIs, CCBs or a combination of these antihypertensive medications.

Cox regression analyses evaluated epilepsy incidence during follow-up by comparing the ARB cohort with other antihypertensive classes. The association between ARB use and epilepsy incidence was examined by subgroup and sensitivity analyses.

The study led to the following findings:

• Of 2 261 964 patients (mean age, 61.7 years; 49.5% female) included, 309 978 received ARBs, 695 887 received β-blockers, 807 510 received ACEIs, and 448 589 received CCBs.
• Demographic and clinical characteristics differed across the four comparison groups before PS matching.
• Compared with ARB users, patients receiving ACEIs were predominantly male and had diabetes, CCB users were generally older (e.g., >65 years), and β-blocker users had more comorbidities and concurrent medications.
• The 1:1 PS-matched subgroups included 619 858 patients for ARB versus ACEI, 619 828 patients for ARB versus β-blocker, and 601 002 patients for ARB vs CCB.
• Baseline characteristics were equally distributed between comparison groups after matching with propensity scores.
• The use of ARBs was associated with a decreased incidence of epilepsy compared with ACEIs (adjusted hazard ratio [aHR], 0.75), β-blockers (aHR, 0.70), and a combination of other antihypertensive classes (aHR, 0.72).
• Subgroup analyses revealed a significant association between ARB use (primarily losartan) and epilepsy incidence in patients with no preexisting history of stroke or cardiovascular disease.

The findings showed that ARBs, mainly losartan, were associated with a lower epilepsy incidence compared with other antihypertensive agents in hypertensive patients with no preexisting cardiovascular disease or stroke.

"Further studies, such as randomized clinical trials, are warranted to confirm the comparative antiepileptogenic properties of antihypertensive medications," the researchers concluded.

Reference:

Wen X, Otoo MN, Tang J, et al. Angiotensin Receptor Blockers for Hypertension and Risk of Epilepsy. JAMA Neurol. Published online June 17, 2024. doi:10.1001/jamaneurol.2024.1714