Concomitant Use of Direct Oral Anticoagulants and Antiepileptic Drugs: A Prospective Cohort Study in Patients with Atria
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ORIGINAL RESEARCH ARTICLE
Concomitant Use of Direct Oral Anticoagulants and Antiepileptic Drugs: A Prospective Cohort Study in Patients with Atrial Fibrillation Michela Giustozzi1 · Matteo Mazzetti2 · Maurizio Paciaroni1 · Giancarlo Agnelli1 · Cecilia Becattini1 · Maria Cristina Vedovati1 Accepted: 24 October 2020 © The Author(s) 2020
Abstract 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 C HA2DS2-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% patientyear). 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.
1 Introduction Direct oral anticoagulants (DOAC) are increasingly replacing vitamin K antagonists (VKA) for the prevention of stroke in atrial fibrillation (AF) and for the treatment of venous thromboembolism. In randomised clinical trials in these clinical settings, DOACs were shown to be non-inferior compared to VKAs concerning efficacy, with the advantage of a reduction in major bleeding [1, 2]. In addition, the use of DOACs in fixed doses without laboratory monitoring has led to an awaited improved practicality. Based on all these issues, current international guidelines recommend DOACs * Michela Giustozzi [email protected]; [email protected] 1
Internal Vascular and Emergency Medicine and Stroke Unit, University of Perugia, Perugia, Italy
Internal Medicine of Montevarchi, University of Florence, Florence, Italy
2
Key Points The risk of epilepsy is double in patients with atrial fibrillation (AF), possibly linked to silent stroke. Thus, a high proportion of patients with AF require the concomitant long-term administration of oral anticoagulation and antiepil
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