Concomitant Use of Direct Oral Anticoagulants and Antiepileptic Drugs: A Prospective Cohort Study in Patients with Atrial Fibrillation

BACKGROUND: European guidelines do not recommend the use of carbamazepine, levetiracetam, phenobarbital, phenytoin, topiramate and valproic acid in patients taking direct oral anticoagulants (DOACs). Little is known regarding the clinical relevance of the interaction between DOACs and antiepileptic drugs. OBJECTIVES: To evaluate the incidence of thromboembolic and bleeding events in patients with non-valvular atrial fibrillation (AF) concurrently treated with DOACs and antiepileptic drugs. METHODS: This is a prospective multicentre cohort study of patients with non-valvular AF concurrently treated with DOACs and antiepileptic drugs. The primary outcome was ischaemic stroke/transient ischaemic attack (TIA)/systemic embolism (SE). Secondary outcome was major bleeding (MB). Incidence rates (% patient-year) were evaluated for the study outcomes. RESULTS: Overall, 91 patients were included. Mean age was 78 ± 9.5 years, 49.5% were female. Mean CHA(2)DS(2)-VASc score was 4.76 ± 1.59 and mean HAS-BLED was 2.67 ± 1.26. Overall, 41, 20, 11, 10 and 9 out of 91 patients were treated with levetiracetam, valproic acid, phenobarbital, carbamazepine and other antiepileptic drugs, respectively. During a median follow-up of 17.5 ± 14.5 months, stroke/TIA/SE occurred in 9 patients (5.7% patient-year) and MB in 3 patients (1.9% patient-year). Ischaemic stroke was fatal in 3 patients (1.9% patient-year) and MB in one patient (0.6% patient-year). CONCLUSION: In this cohort, patients with non-valvular AF treated with DOACs and antiepileptic drugs appear to have a relatively high rate of thromboembolic events.