Huang Yu-Ting, Chen Tzu-Ling, Huang Yun-Lin, Kuo Ching-Hua, Peng Yu-Fong, Tang Sung-Chun, Jeng Jiann-Shing, Huang Chih-Feng, Lin Shin-Yi, Lin Fang-Ju
Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan.
School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan.
Front Pharmacol. 2025 Feb 19;16:1505665. doi: 10.3389/fphar.2025.1505665. eCollection 2025.
This purpose of this study is to analyze the influence of levetiracetam (LEV) on direct oral anticoagulant (DOAC) exposure and its implications for clinical outcomes.
This investigation comprised a retrospective cohort study utilizing the integrated medical database and a prospective observational study conducted in a tertiary hospital. Patients aged >65 years with atrial fibrillation and undergoing DOAC therapy were included and were categorized as LEV users and non-users based on LEV exposure status. In retrospective cohort, clinical outcomes between LEV users and non-users were compared, included ischemic stroke or transient ischemic attack (IS/TIA), systemic thromboembolism (STE) and major bleeding. In prospective cohort, DOAC trough concentration was measured.
The retrospective study included 191 LEV users and 694 matched LEV non-users. The risk of IS/TIA and STE were not significantly different between two groups (hazard ratio [HR], 0.99 [0.51-1.91] and 0.94 [0.49-1.79], respectively). For major bleeding, a non-significant higher risk was observed in the LEV-user group in contrast to the LEV-non-user group (HR 2.65 [0.43, 16.33]). The prospective analysis included 19 LEV users and 76 matched LEV non-users. Low DOAC concentrations were observed in 5.3% of LEV-users and 14.5% of LEV non-users ( = 0.53). High DOAC concentration were observed in 10.5% of LEV-users and 11.8% LEV non-users (P = 0.57). The association between LEV therapy and low or high DOAC concentration was non-significant.
Concurrent use of LEV and DOAC did not significantly affect DOAC exposure or clinical outcomes. LEV may be a safe anti-seizure medication for patients receiving DOAC therapy.
本研究旨在分析左乙拉西坦(LEV)对直接口服抗凝剂(DOAC)血药浓度的影响及其对临床结局的意义。
本研究包括一项利用综合医疗数据库的回顾性队列研究和一项在三级医院进行的前瞻性观察性研究。纳入年龄>65岁且正在接受DOAC治疗的房颤患者,并根据是否使用LEV将其分为LEV使用者和非使用者。在回顾性队列中,比较LEV使用者和非使用者之间的临床结局,包括缺血性卒中或短暂性脑缺血发作(IS/TIA)、系统性血栓栓塞(STE)和大出血。在前瞻性队列中,测定DOAC谷浓度。
回顾性研究纳入了191名LEV使用者和694名匹配的LEV非使用者。两组之间IS/TIA和STE的风险无显著差异(风险比[HR]分别为0.99[0.51 - 1.91]和0.94[0.49 - 1.79])。对于大出血,与LEV非使用者组相比,LEV使用者组观察到的风险虽无显著差异但略高(HR 2.65[0.43, 16.33])。前瞻性分析纳入了19名LEV使用者和76名匹配的LEV非使用者。5.3%的LEV使用者和14.5%的LEV非使用者观察到低DOAC浓度(P = 0.53)。10.5%的LEV使用者和11.8%的LEV非使用者观察到高DOAC浓度(P = 0.57)。LEV治疗与低或高DOAC浓度之间的关联不显著。
同时使用LEV和DOAC对DOAC血药浓度或临床结局无显著影响。对于接受DOAC治疗的患者,LEV可能是一种安全的抗癫痫药物。