Non-vitamin K Oral Anticoagulants and Anti-seizure Medications: A Retrospective Cohort Study

Chen Jui Ho, Shih Hsuan Chen, Chih Hsiang Lin, Yan Ting Lu, Che Wei Hsu, Meng Han Tsai*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

7 Scopus citations


Purpose: 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. Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish
Article number588053
JournalFrontiers in Neurology
StatePublished - 26 02 2021

Bibliographical note

Publisher Copyright:
© Copyright © 2021 Ho, Chen, Lin, Lu, Hsu and Tsai.


  • ASM
  • NOAC
  • drug–drug interaction
  • epilepsy
  • stroke


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