Safety and effectiveness of oral factor Xa inhibitors versus warfarin in nonvalvular atrial fibrillation patients at high-risk for falls

Prescribers' concern regarding falls resulting in intracranial hemorrhage is often cited as a justification for under-utilization of oral anticoagulation. We evaluated the safety and effectiveness of oral factor Xa inhibitors versus warfarin in nonvalvular atrial fibrillation patients at high-risk for falls. Using MarketScan claims from 11/2012-3/2017, we identified adult, oral anticoagulation-naive, new-initiators of oral factor Xa inhibitors or warfarin with nonvalvular atrial fibrillation, >= 12 months of insurance coverage prior to starting oral anticoagulation and a predicted 2-year risk of falls >= 15%. Differences in baseline covariates between cohorts were balanced using inverse probability-of-treatment weights based on propensity scores. Hazard ratios (HRs) and 95% confidence intervals (CIs) for intracranial hemorrhage and stroke or systemic embolism were estimated. Among 25,144 nonvalvular atrial fibrillation patients at high-risk for falls (observed fall rate = 11.8%/person-year), oral factor Xa inhibitor use was associated with a 43% (95% CI = 5-65%) reduced hazard of intracranial hemorrhage compared to warfarin. Oral factor Xa inhibitors did not significantly reduce the hazard of stroke or systemic embolism versus warfarin (HR = 0.86, 95% CI = 0.66-1.11). Findings for the intracranial hemorrhage and stroke or systemic embolism endpoints were similar when apixaban and rivaroxaban were evaluated separately versus warfarin (p-interaction >= 0.64 for all). Oral factor Xa inhibitors reduced patients' risk of intracranial hemorrhage and were at least as effective in preventing stroke or systemic embolism as warfarin in nonvalvular atrial fibrillation patients at high-risk for falls.