ImportanceDirect-acting oral anticoagulants (DOACs) are commonly prescribed with antiseizure medications (ASMs) due to concurrency of and the association between atrial fibrillation (AF) and epilepsy. However, enzyme-inducing (EI) ASMs may reduce absorption and accelerate metabolism of DOACs, potentially lowering DOAC levels and elevating thromboembolism risk.ObjectiveTo assess the rates of thromboembolic and major bleeding events in adults with AF and epilepsy dispensed DOACs and EI ASMs vs DOACs with non-EI ASMs.Design, Setting, and ParticipantsThis active-comparator, new-user cohort study included US health care data from the Clinformatics Data Mart database from October 2010 to September 2021 for a nationally representative population of adults with AF and epilepsy.ExposureEvaluations included episodes of contiguous coadministration of DOACs for AF with EI ASMs (exposed) or non-EI ASMs (referent) for epilepsy.Main Outcomes and MeasuresThromboembolic events (primary outcome) and major bleeding events (secondary outcome) were identified based on a series of validated, diagnosis-based coding algorithms. Data-adaptive, high-dimensional propensity score matching was used to control for observed confounders and proxies for unobserved confounders. Adjusted hazard ratios (AHRs) were estimated using Cox proportional hazards regression models with robust variance estimators to account for clustering within matched pairs.ResultsThis study included 14 078 episodes (median age, 74 [IQR, 67-81]; 52.4% female) and 14 158 episodes (median age, 74 [IQR, 67-81]; 52.4% female) of incident DOAC and ASM use that met eligibility criteria for assessment of thromboembolic and major bleeding outcomes, respectively. Incidence was 88.5 per 1000 person-years for thromboembolic events and 68.3 per 1000 person-years for bleeding events. Compared with use of non-EI ASMs, use of EI ASMs with DOACs was not associated with a difference in risk of thromboembolic events (AHR, 1.10; 95% CI, 0.82-1.46) but was associated with a reduction in risk of major bleeding events (AHR, 0.63; 95% CI, 0.44-0.89).Conclusions and RelevanceIn this cohort study, EI ASMs were not associated with alteration in DOAC efficacy. Further research is needed on the reduction in bleeding risk associated with EI ASMs, as this may suggest that pharmacokinetic interactions are associated with lowering DOAC levels without negating therapeutic effects.

中文翻译：

---

直接作用口服抗凝剂和抗癫痫药物治疗心房颤动和癫痫以及血栓栓塞事件的风险


重要性 由于心房颤动 (AF) 与癫痫同时存在且两者之间存在关联，直接作用口服抗凝剂 (DOAC) 通常与抗癫痫药物 (ASM) 一起使用。然而，酶诱导 (EI) ASM 可能会减少 DOAC 的吸收并加速其代谢，从而可能降低 DOAC 水平并增加血栓栓塞风险。 目的 评估 AF 和癫痫成人配发 DOAC 和 EI ASM 与 DOAC 的血栓栓塞和大出血事件发生率设计、设置和参与者这项主动比较的新用户队列研究包括来自 Clinformatics Data Mart 数据库的 2010 年 10 月至 2021 年 9 月期间针对全国代表性的 AF 和癫痫成人人群的美国医疗保健数据。暴露评估包括连续联合使用 DOAC 治疗 AF 与 EI ASM（暴露）或非 EI ASM（参考）治疗癫痫的发作。主要结果和措施基于一系列结果确定了血栓栓塞事件（主要结果）和主要出血事件（次要结果）经过验证的、基于诊断的编码算法。数据自适应、高维倾向评分匹配用于控制观察到的混杂因素和未观察到的混杂因素的代理。使用带有稳健方差估计器的 Cox 比例风险回归模型来估计调整后的风险比 (AHR)，以解释匹配对内的聚类。结果本研究包括 14 078 次发作（中位年龄 74 [IQR，67-81]；52.4% 女性）和14 158 次 DOAC 和 ASM 使用事件（中位年龄 74 岁 [IQR，67-81]；52.4% 女性）分别符合血栓栓塞和大出血结局评估的资格标准。血栓栓塞事件的发生率为每 1000 人年 88.5 例，每 1000 人年为 68 例。每 1000 人年有 3 例发生出血事件。与使用非 EI ASM 相比，EI ASM 与 DOAC 的使用与血栓栓塞事件风险差异无关（AHR，1.10；95% CI，0.82-1.46），但与大出血风险降低相关事件（AHR，0.63；95% CI，0.44-0.89）。结论和相关性在这项队列研究中，EI ASM 与 DOAC 疗效的改变无关。需要对与 EI ASM 相关的出血风险降低进行进一步研究，因为这可能表明药代动力学相互作用与降低 DOAC 水平相关，但不会抵消治疗效果。