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.