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

Abstract

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. Methods: 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. Results: 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. Conclusion: 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.