Major Bleeding Complications and Persistence With Oral Anticoagulation in Non‐Valvular Atrial Fibrillation: Contemporary Findings in Real‐Life Danish Patients

Background The nonvitamin K antagonist oral anticoagulants have recently become available as an alternative to warfarin as stroke prophylaxis in atrial fibrillation, but data on real‐life patient experience, including bleeding risk, are lacking. Our objective was to compare major bleeding events and nonpersistence between the nonvitamin K antagonist oral anticoagulant apixaban and other nonvitamin K antagonist oral anticoagulants (dabigatran and rivaroxaban) and warfarin in a contemporary, nation‐wide cohort of patients with nonvalvular atrial fibrillation. Methods and Results Of 54 321 patients (median age, 73 years; 56% male; mean CHA 2 DS 2 ‐ VAS c score, 2.9), 7963, 6715, 15 413, and 24 230 patients initiated apixaban, rivaroxaban, dabigatran, and warfarin, respectively. Apixaban and rivaroxaban initiators were older, less often male, with higher HAS ‐ BLED and CHA 2 DS 2 ‐ VAS c scores compared with dabigatran and warfarin initiators. A total of 2418 patients (4.5%) experienced a major bleeding event over all available follow‐up. In this period, rivaroxaban (hazard ratio HR 95% CI, 1.49 1.27–1.77), dabigatran ( HR , 1.17 1.00–1.38), and warfarin ( HR , 1.23 1.05–1.43) users were significantly more likely to bleed than apixaban users. Findings were similar when restricted to the first 30 days after OAC initiation. Risk of nonpersistence was higher for dabigatran ( HR , 1.45 1.33–1.59) and warfarin initiators ( HR , 1.22 1.12–1.33), but not for rivaroxaban initiators ( HR , 1.07 0.96–1.20) compared with apixaban initiators. Conclusions In a real‐world cohort of nonvalvular atrial fibrillation patients, apixaban had a lower adjusted major bleeding risk compared with rivaroxaban, dabigatran, and warfarin. Apixaban had a lower risk of nonpersistence compared with dabigatran and warfarin and similar risk compared with rivaroxaban.