Ho Chen-Jui, Chen Shih-Hsuan, Lin Chih-Hsiang, Lu Yan-Ting, Hsu Che-Wei, Tsai Meng-Han
Department of Neurology, College of Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, Kaohsiung, Taiwan.
School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Front Neurol. 2021 Feb 26;11:588053. doi: 10.3389/fneur.2020.588053. eCollection 2020.
Concerns of drug-drug interactions (DDIs) between anti-seizure medications (ASMs) and non-vitamin K oral anticoagulants (NOACs) have emerged in recent case reports and guidelines. Theoretically, the induction of hepatic cytochrome P450 3A4 (CYP3A4) enzyme and permeability glycoprotein (P-GP) efflux transporter protein systems may reduce the effect of NOACs. We aimed to investigate whether such DDIs are clinically relevant in a real-world situation. We retrospectively reviewed 320 ischemic stroke patients with atrial fibrillation (Af) and grouped them according to different potential interactions with CYP3A4 and P-GP. Ischemic stroke events, transient ischemic attack (TIA) events, follow-up duration, baseline characteristics, concomitant ASMs, and stroke risk factors were collected. Statistical analysis included Kaplan-Meier survival curves and the log-rank test. Overall, 320 ischemic stroke with Af patients received NOACs. Among the NOAC users, 75 also took ASMs, including 56 that have potential DDIs: 43 (13.4%) were categorized as potential CYP and P-GP DDIs and 13 (4.1%) as P-GP-only DDIs. The remaining 264 (82.5%) patients were used as controls including 19 exposed to nonsignificant DDI ASMs and 245 patients without ASM exposure. The incidence rates of recurrent stroke/TIA events in both CYP3A4 and P-GP DDIs, P-GP DDIs only, and no DDIs were 7.5, 2.1, and 8.4/100 person-years, respectively. Kaplan-Meier survival curves and the log-rank test did not show significant differences among the groups. The recurrent stroke rate of NOAC users with potential DDIs was not higher than in those without potential DDIs in this single-institute study. Our results suggest that theoretical interactions between ASMs and NOACs may not be as severe as previously thought in a real-world situation.
近期的病例报告和指南中出现了关于抗癫痫药物（ASMs）与非维生素K口服抗凝药（NOACs）之间药物相互作用（DDIs）的担忧。从理论上讲，肝细胞色素P450 3A4（CYP3A4）酶和通透性糖蛋白（P-GP）外流转运蛋白系统的诱导可能会降低NOACs的效果。我们旨在调查这种药物相互作用在实际临床情况中是否具有相关性。我们回顾性分析了320例患有房颤（Af）的缺血性中风患者，并根据与CYP3A4和P-GP的不同潜在相互作用进行分组。收集了缺血性中风事件、短暂性脑缺血发作（TIA）事件、随访时长、基线特征、同时服用的抗癫痫药物以及中风风险因素。统计分析包括Kaplan-Meier生存曲线和对数秩检验。总体而言，320例患有房颤的缺血性中风患者接受了NOACs治疗。在服用NOACs的患者中，75人同时服用了抗癫痫药物，其中56人存在潜在的药物相互作用：43人（13.4%）被归类为潜在的CYP和P-GP药物相互作用，13人（4.1%）为仅P-GP药物相互作用。其余264例（82.5%）患者作为对照，其中19例暴露于无显著药物相互作用的抗癫痫药物，245例未暴露于抗癫痫药物。CYP3A4和P-GP药物相互作用组、仅P-GP药物相互作用组以及无药物相互作用组的复发性中风/TIA事件发生率分别为7.5、2.1和8.4/100人年。Kaplan-Meier生存曲线和对数秩检验未显示各组之间存在显著差异。在这项单机构研究中，存在潜在药物相互作用的NOACs使用者的复发性中风率并不高于无潜在药物相互作用的使用者。我们的结果表明，在实际临床情况中，抗癫痫药物与NOACs之间的理论相互作用可能并不像之前认为的那么严重。
