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Original Investigation
June 17, 2024

Angiotensin Receptor Blockers for Hypertension and Risk of Epilepsy

Author Affiliations
  • 1Department of Pharmacy Practice and Clinical Research, College of Pharmacy, University of Rhode Island, Kingston
  • 2Department of Nephrology, The Warren Alpert Medical School of Brown University, Providence, Rhode Island
  • 3Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, California
JAMA Neurol. Published online June 17, 2024. doi:10.1001/jamaneurol.2024.1714
Key Points

Question  What is the risk of incident epilepsy in patients with hypertension receiving angiotensin receptor blockers (ARBs) compared with those using angiotensin-converting enzyme inhibitors (ACEIs), β-blockers, or calcium channel blockers (CCBs)?

Findings  This cohort study of 2 261 964 patients used propensity score matching to assess 619 858 patients for ARB vs ACEI, 619 828 patients for ARB vs β-blocker, and 601 002 patients for ARB vs CCB. Use of ARBs was associated with a lower incidence of epilepsy compared with ACEIs and β-blockers.

Meaning  These findings suggest that ARBs were associated with a lower incidence of new-onset epilepsy compared with other antihypertensive agents in patients with hypertension.

Abstract

Importance  Animal and human studies have suggested that the use of angiotensin receptor blockers (ARBs) may be associated with a lower risk of incident epilepsy compared with other antihypertensive medications. However, observational data from the US are lacking.

Objective  To evaluate the association between ARB use and epilepsy incidence in subgroups of US patients with hypertension.

Design, Setting, and Participants  This retrospective cohort study used data from a national health administrative database from January 2010 to December 2017 with propensity score (PS) matching. The eligible cohort included privately insured individuals aged 18 years or older with diagnosis of primary hypertension and dispensed at least 1 ARB, angiotensin-converting enzyme inhibitor (ACEI), β-blocker, or calcium channel blocker (CCB) from 2010 to 2017. Patients with a diagnosis of epilepsy at or before the index date or dispensed an antiseizure medication 12 months before or 90 days after initiating the study medications were excluded. The data analysis for this project was conducted from April 2022 to April 2024.

Exposures  Propensity scores were generated based on baseline covariates and used to match patients who received ARBs with those who received either ACEIs, β-blockers, CCBs, or a combination of these antihypertensive medications.

Main Outcomes and Measures  Cox regression analyses were used to evaluate epilepsy incidence during follow-up comparing the ARB cohort with other antihypertensive classes. Subgroup and sensitivity analyses were conducted to examine the association between ARB use and epilepsy incidence in various subgroups.

Results  Of 2 261 964 patients (mean [SD] age, 61.7 [13.9] years; 1 120 630 [49.5%] female) included, 309 978 received ARBs, 807 510 received ACEIs, 695 887 received β-blockers, and 448 589 received CCBs. Demographic and clinical characteristics differed across the 4 comparison groups prior to PS matching. Compared with ARB users, patients receiving ACEIs were predominantly male and had diabetes, CCB users were generally older (eg, >65 years), and β-blocker users had more comorbidities and concurrent medications. The 1:1 PS-matched subgroups included 619 858 patients for ARB vs ACEI, 619 828 patients for ARB vs β-blocker, and 601 002 patients for ARB vs CCB. Baseline characteristics were equally distributed between comparison groups after matching with propensity scores. Use of ARBs was associated with a decreased incidence of epilepsy compared with ACEIs (adjusted hazard ratio [aHR], 0.75; 95% CI, 0.58-0.96), β-blockers (aHR, 0.70; 95% CI, 0.54-0.90), and a combination of other antihypertensive classes (aHR, 0.72; 95% CI, 0.56-0.95). 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.

Conclusions and Relevance  This cohort study found that ARBs, mainly losartan, were associated with a lower incidence of epilepsy compared with other antihypertensive agents in hypertensive patients with no preexisting stroke or cardiovascular disease. Further studies, such as randomized clinical trials, are warranted to confirm the comparative antiepileptogenic properties of antihypertensive medications.

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