Edoxaban versus warfarin in vitamin K antagonist experienced and naïve patients from the edoxaban versus warfarin in subjects undergoing cardioversion of atrial fibrillation (ENSURE-AF) randomised trial

Abstract

Background: In ENSURE-AF study, edoxaban had similar efficacy and safety profile versus enoxaparin–warfarin (enox–warf) in patients undergoing electrical cardioversion of non-valvular atrial fibrillation. Objectives: To evaluate the efficacy and safety of edoxaban versus enox–warf in patients who were vitamin K antagonists (VKA) naïve or experienced at time of randomisation into ENSURE-AF trial. Methods: The primary efficacy endpoint was a composite of stroke, systemic embolic event, myocardial infarction, and cardiovascular death during the overall study period, 28 days on study drug after cardioversion and 30 days follow-up. The primary safety endpoint was the composite of major and clinically relevant nonmajor bleeding during the on-medication period from time of first dose to last dose of study drug taken + 3 days. Results: Of 2199 patients enrolled in ENSURE-AF, 1095 were randomised to edoxaban and 1104 to enox–warf. There were numerically fewer primary efficacy endpoint events with edoxaban than enox–warf irrespective of whether VKA experienced or naïve (0.5% vs. 0.9%, 0.3% vs. 1.4%, respectively). There were no significant differences in the primary safety endpoint [odds ratio (OR) 2.09, 95% confidence interval (CI) 0.72–6.81 in anticoagulant experienced patients, OR 0.77, 95% CI 0.15–3.60 in anticoagulant naïve patients] and in major bleeding rates regardless of treatment or VKA experience (OR 0.69, 95%CI 0.06–6.04, OR 0.48, 95% CI 0.01–9.25, respectively). Conclusions: Edoxaban had comparable efficacy and safety to optimized anticoagulation with enox–warf. The primary efficacy and safety endpoint outcomes were broadly similar between VKA experienced or naïve patients.