Co-administration of anti-seizure medications with potential CYP3A4 and/or P-GP interactions did not significantly increase the incidence of recurrent stroke or TIA compared to controls in patients taking NOACs (7.3 vs. 7.4 per 100 person-years, p=0.809).
Cohort (n=320)
No
Does the co-administration of CYP3A4 or P-GP inducing anti-seizure medications with NOACs increase the risk of recurrent stroke or TIA in patients with atrial fibrillation?
Theoretical drug-drug interactions between NOACs and anti-seizure medications (CYP3A4/P-GP inducers) did not translate to a higher risk of recurrent stroke in a real-world cohort of atrial fibrillation patients.
Absolute Event Rate: 7.3% vs 7.4%
p-value: p=0.809
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.
Ho et al. (2021) conducted a cohort in Ischemic stroke with atrial fibrillation (n=320). NOACs with CYP3A4 and/or P-GP inducing anti-seizure medications vs. NOACs without interacting anti-seizure medications was evaluated on Any ischemic stroke or TIA event during follow-up (p=0.809). Co-administration of anti-seizure medications with potential CYP3A4 and/or P-GP interactions did not significantly increase the incidence of recurrent stroke or TIA compared to controls in patients taking NOACs (7.3 vs. 7.4 per 100 person-years, p=0.809).