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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Pharmacoepidemiology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1505665

Impact of levetiracetam on direct oral anticoagulant level and outcomes among older Asian patients with atrial fibrillation

Provisionally accepted
Yu-Ting Huang Yu-Ting Huang 1Tzu-Ling Chen Tzu-Ling Chen 2Yun-Lin Huang Yun-Lin Huang 2Ching-Hua Kuo Ching-Hua Kuo 2Yu-Fong Peng Yu-Fong Peng 2Sung-chun Tang Sung-chun Tang 3Jiann-Shing Jeng Jiann-Shing Jeng 3Chih-Fen Huang Chih-Fen Huang 1,2,4Lin Shin Yi Lin Shin Yi 1,2*Fang-Ju Lin Fang-Ju Lin 1,2,4
  • 1 National Taiwan University Hospital, Taipei, Taiwan
  • 2 School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan
  • 3 Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan
  • 4 Graduate Institute of Clinical Pharmacy, School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan

The final, formatted version of the article will be published soon.

    Objective: 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 (P=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.

    Keywords: direct oral anticoagulants, levetiracetam, Drug Interaction, Elderly, Thromboembolism, bleeding

    Received: 04 Oct 2024; Accepted: 27 Jan 2025.

    Copyright: © 2025 Huang, Chen, Huang, Kuo, Peng, Tang, Jeng, Huang, Shin Yi and Lin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Lin Shin Yi, School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.