BackgroundDespite many atrial fibrillation (AF) patients being at risk of bleeding, very limited data are available on bleeding rates of different direct oral anticoagulants (DOACs) based on the spectrum of bleeding risk. ObjectiveTo compare the risk of major bleeding and thromboembolic events with apixaban versus rivaroxaban among AF patients, stratified by bleeding risk. MethodsWe conducted a population-based, retrospective cohort study of all adult patients (66 years or older) with AF in Ontario, Canada, who were treated with apixaban or rivaroxaban between April 1, 2011 and March 31, 2020. Bleeding risk was estimated using the HAS-BLED score with high bleeding risk defined as a score of 3 or greater. The primary safety outcome was major bleeding and the primary efficacy outcome was thromboembolic events. Comparisons were adjusted for baseline comorbidities using inverse probability of treatment weighting (IPTW). ResultsThis study included 18,156 AF patients with high bleeding risk and 55,186 AF patients with low bleeding risk. Apixaban use was more common in high bleeding risk patients; 63% of high risk patients used apixaban compared to 56% of low risk patients. Apixaban users had lower rates of major bleeding in high risk patients (2.9% vs 4.2% per year; HR 0.69 [95%CI, 0.58-0.81]) and in low risk patients (1.8% vs 2.9% per year; HR 0.63 [95%CI, 0.56-0.70]), compared with rivaroxaban. There were no differences in rates of thromboembolic events 3.1% vs 3.0% per year (HR 1.02 [95%CI, 0.86-1.22]) in high risk patients and 1.9% vs 1.9% per year (HR 1.00 [95%CI, 0.89-1.14]) in low risk patients. ConclusionsAmong older AF patients with high or low bleeding risk, treatment with apixaban was associated with lower rates of major bleeding with no difference in risk for thromboembolic events compared with rivaroxaban.