Comparing Major Bleeding Risk in Outpatients With Atrial Fibrillation or Flutter by Oral Anticoagulant Type (from the National Cardiovascular Disease Registry's Practice Innovation and Clinical Excellence Registry)

•DOACs have a favorable bleeding safety profile relative to warfarin.•The bleeding safety profile associated with individual DOACs are not identical.•Rivaroxaban was associated with higher gastrointestinal bleeding risk relative to warfarin.•DOAC users 75 years and older had less safety benefit relative to warfarin users. Direct oral anticoagulants (DOACs) have a favorable bleeding risk profile in patients with atrial fibrillation (AF). However, the safety of individual DOACs relative to warfarin for specific bleeding outcomes is less certain. We identified 423,450 patients with AF between 2013 to 2015 in the NCDR PINNACLE national ambulatory registry matched to the Centers for Medicare and Medicaid Services database. Outcomes included time to first major bleed, intracranial hemorrhage (ICH), major gastrointestinal bleed (GIB), or other major bleed. We estimated the association of OAC with bleeding using Cox proportional hazard models. The median duration of follow-up was 1.4 years. OACs were used in 64% of AF patients (66% warfarin, 15% rivaroxaban, 12% dabigatran, and 7% apixaban). A major bleeding event occurred in 6.9% of patients. Compared with warfarin users, fewer patients experienced ICH with the use of rivaroxaban (HR 0.73; 95% CI 0.64 to 0.84), dabigatran (HR 0.56; 95% CI 0.48 to 0.65), and apixaban (HR 0.70; 95% CI 0.55 to 0.90). The risk of major GIB was higher in rivaroxaban users (HR 1.20; 95% CI 1.12 to 1.27), and lower in dabigatran (HR 0.88; 95% CI 0.82 to 0.95) and apixaban (HR 0.84; 95% CI 0.74 to 0.95) users. For any DOAC versus warfarin, age (≥75 or