Bergmark BA, Kamphuisen PW, Wiviott SD, et al. - In the ENGAGE AF (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation)-TIMI 48 trial of edoxaban vs warfarin, researchers evaluated bleeding outcomes as per the ISTH, TIMI, GUSTO, and BARC bleeding scales among 21,105 patients with atrial fibrillation (AF) at risk for stroke (CHADS₂ ≥ 2). Warfarin was compared with a higher (60/30 mg daily) or lower (30/15 mg daily) dose edoxaban regimen. Participants were observed over a median duration of 2.8 years. When the most severe events in each scale were compared, ISTH Major bleeding was identified as the most frequent (n = 1,289) followed by TIMI Major (n = 548), GUSTO Severe/Life-Threatening (n = 347), and BARC 3c+5 (n = 276). Irrespective of bleeding scale, edoxaban vs warfarin was associated with lower bleeding risk. Overall, the frequency of the most severe bleeding events varied nearly four-fold across commonly used bleeding scales in this patient populace of AF patients at risk for stroke. A rise in the relative safety of edoxaban vs warfarin was seen with greater severity of bleeding.