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The comparative effectiveness of rivaroxaban and apixaban, the most frequently prescribed oral anticoagulants for ischemic stroke prevention in patients with atrial fibrillation, is uncertain. To compare major ischemic and hemorrhagic outcomes in patients with atrial fibrillation treated with rivaroxaban or apixaban. Retrospective cohort study using computerized enrollment and claims files for US Medicare beneficiaries 65 years or older. Between January 1, 2013, and November 30, 2018, a total of 581 451 patients with atrial fibrillation