Background: Although apixaban and rivaroxaban are commonly used in patients with atrial fibrillation (AF) and valvular heart disease (VHD), there is limited evidence comparing the 2 drugs in these patients.

Objective: To emulate a target trial of effectiveness and safety of apixaban and rivaroxaban in patients with AF and VHD.

Design: New-user, active comparator, cohort study design.

Setting: Commercial health insurance database from 1 January 2013 to 31 December 2020.

Patients: New users of apixaban or rivaroxaban who had a diagnosis of AF and VHD before initiation of anticoagulant therapy.

Measurements: The primary effectiveness outcome was a composite of ischemic stroke or systemic embolism. The primary safety outcome was a composite of gastrointestinal or intracranial bleeding. Cox proportional hazards regression with a robust variance estimator was used to estimate hazard ratios (HRs) and 95% CIs.

Results: When compared with rivaroxaban in a propensity score-matched cohort of 19 894 patients (9947 receiving each drug), apixaban was associated with a lower rate of ischemic stroke or systemic embolism (HR, 0.57 [95% CI, 0.40 to 0.80]) and bleeding (HR, 0.51 [CI, 0.41 to 0.62]). The absolute reduction in the probability of stroke or systemic embolism with apixaban compared with rivaroxaban was 0.0026 within 6 months and 0.011 within 1 year of treatment initiation. The absolute reduction in the probability of bleeding events with apixaban compared with rivaroxaban was 0.012 within 6 months and 0.019 within 1 year of treatment initiation.

Limitation: Short follow-up time and inability to ascertain some types of VHD.

Conclusion: In this study of patients with AF and VHD, patients receiving apixaban had a lower risk for ischemic stroke or systemic embolism and for bleeding when compared with those receiving rivaroxaban.

Primary funding source: National Institutes of Health.