ImportanceAnimal 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.ObjectiveTo evaluate the association between ARB use and epilepsy incidence in subgroups of US patients with hypertension.Design, Setting, and ParticipantsThis 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.ExposuresPropensity 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 MeasuresCox 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.ResultsOf 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 RelevanceThis 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.

中文翻译：

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血管紧张素受体阻滞剂治疗高血压和癫痫风险


重要性动物和人类研究表明，与其他抗高血压药物相比，使用血管紧张素受体阻滞剂 (ARB) 可能会降低癫痫发作的风险。然而，缺乏来自美国的观察数据。目的评估美国高血压患者亚组中 ARB 使用与癫痫发病率之间的关联。设计、设置和参与者这项回顾性队列研究使用了 2010 年 1 月至 12 月国家卫生行政数据库的数据2017 年倾向得分 (PS) 匹配。符合条件的队列包括年龄 18 岁或以上、诊断为原发性高血压并在 2010 年至 2017 年期间至少服用 1 种 ARB、血管紧张素转换酶抑制剂 (ACEI)、β 受体阻滞剂或钙通道阻滞剂 (CCB) 的私人保险个人。在索引日期或之前诊断出癫痫或在开始研究药物之前 12 个月或之后 90 天服用抗癫痫药物的患者被排除在外。该项目的数据分析于 2022 年 4 月至 2024 年 4 月进行。暴露倾向评分是根据基线协变量生成的，用于将接受 ARB 治疗的患者与接受 ACEI、β 受体阻滞剂、CCB 或这些抗高血压药物组合治疗的患者进行匹配主要结果和措施 Cox 回归分析用于评估随访期间癫痫的发生率，比较 ARB 队列与其他抗高血压药物。进行亚组和敏感性分析，以检查不同亚组中 ARB 使用与癫痫发病率之间的关联。 结果 2 261 964 名患者（平均 [SD] 年龄，61.7 [13.9] 岁；1 120 630 名患者[49。5%]女性），其中 309 978 人接受了 ARB 治疗，807 510 人接受了 ACEI 治疗，695 887 人接受了 β 受体阻滞剂治疗，448 589 人接受了 CCB 治疗。在 PS 匹配之前，4 个比较组的人口统计学和临床​​特征存在差异。与ARB使用者相比，接受ACEIs的患者主要是男性并患有糖尿病，CCB使用者通常年龄较大（例如，>65岁），并且β-受体阻滞剂使用者有更多的合并症和同时用药。 1:1 PS 匹配亚组包括 619 858 名接受 ARB 与 ACEI 治疗的患者、619 828 名接受 ARB 与 β 受体阻滞剂治疗的患者以及 601 002 名接受 ARB 与 CCB 治疗的患者。与倾向评分匹配后，基线特征在对照组之间均匀分布。与 ACEI 相比，使用 ARB 可以降低癫痫发生率（调整后风险比 [aHR]，0.75；95% CI，0.58-0.96）、β 受体阻滞剂（aHR，0.70；95% CI，0.54-0.90）以及其他抗高血压药物的组合（aHR，0.72；95% CI，0.56-0.95）。亚组分析显示，对于既往无中风或心血管疾病史的患者，使用 ARB（主要是氯沙坦）与癫痫发病率之间存在显着相关性。结论和相关性本队列研究发现，与其他药物相比，ARB（主要是氯沙坦）与癫痫发病率较低相关。对于既往无中风或心血管疾病的高血压患者，可使用其他抗高血压药物。有必要进行进一步的研究，例如随机临床试验，以确认抗高血压药物的相对抗癫痫特性。