Comparative effectiveness and safety of oral anticoagulants for atrial fibrillation: A retrospective cohort study.

Oral anticoagulants (OACs) are high-priority medications, frequently used with clinically important benefit and serious harm. Our objective was to compare the safety and effectiveness of direct-acting oral anticoagulants (DOACs) versus warfarin in a population where anticoagulation management and DOACs were readily available. A retrospective cohort study of all adults living in British Columbia with a diagnosis of atrial fibrillation and a first prescription for an OAC was conducted. Co-primary outcomes were ischemic stroke and systemic embolism, and major bleeding. Secondary outcomes included a net clinical outcome composite and analysis of discontinuation, switching, and key subgroups. We estimated the effects of treatment using time-to-event models with high-dimensional propensity score adjustment to control confounding. After adjustment for prescribing bias, a cohort (n = 20,113, 43.8% female, mean age 72.4 years) with a mean follow-up of 18.1 months showed that patients taking warfarin tended to be poorer, sicker, and less likely to have a cardiologist prescriber. Outcome event rates were not significantly different for DOACs compared to warfarin [adjusted rate ratio of 1.15 (0.91, 1.46) for systemic embolism, 0.94 (0.82, 1.08) for major bleeding, and 0.98 (0.90, 1.06) for net clinical outcome]. Only the effect of age on net clinical outcome met our strict criteria for predicting which group might be superior. Switch of drug class was associated with increased risk of events (p < 0.003). In this population, we found no difference in important clinical outcomes between warfarin and DOACs. Switching compared to not switching was associated with harm.