Abstract 16903: Predictors of Major Bleeding Risk: Insights from the Rivaroxaban Once-Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF)

Background: AF is associated with increased ischemic stroke risk. Oral anticoagulation reduces this risk, but there is often suboptimal use of stroke prophylaxis among AF patients, which may be due to challenges in risk stratification for bleeding. Methods: We investigated factors associated with bleeding in 14,264 pts with nonvalvular AF randomized to rivaroxaban or dose-adjusted warfarin in ROCKET AF. Endpoints of interest were ISTH-defined major bleeding events, intracranial and fatal bleeding. Cox proportional hazards modeling was used to identify factors associated with major bleeding. Results: Over a median follow-up of 1.94 yrs, a major bleed occurred in 395 (5.55%; 3.60 per 100-pt yrs) pts assigned rivaroxaban and 386 (5.42%; 3.45 per 100-pt yrs) assigned warfarin (HR 1.04, 95% CI 0.90, 1.20). Intracranial (0.49% vs. 0.74% per yr; p=0.019) and fatal bleeding (0.24% vs. 0.48% per yr; p=0.003) were lower with rivaroxaban. Pts (n=781) with a major bleed were more likely to be older (median 75 vs. 73 yrs), smokers (40 vs. 33%), and with lower baseline calculated CrCl (median 63 vs. 68 mL/min); less likely to be female (34 vs. 40%) and have a prior stroke/TIA (46 vs. 53%) (all p<0.002) compared with those without a major bleed (n=13,455). Increased age, male sex, BMI, history of diabetes and COPD, and decreased calculated CrCl were independent predictors of increased risk for major bleeding (C-index=0.62). No significant interaction was identified between predictors of bleeding and components of major bleeding. Conclusions: Major bleeding rates were similar with rivaroxaban or warfarin; however, intracranial and fatal bleeding was significantly lower with rivaroxaban. Older age, male sex, prior diabetes, increased BMI, lower diastolic BP, and reduced renal function at baseline were independently associated with major bleeding. Careful assessment of bleeding risk in patients with AF is required to support clinical decision making for stroke prevention therapy.