Risks of Stroke and Mortality in Atrial Fibrillation Patients Treated With Rivaroxaban and Warfarin

Background and Purpose— Oral anticoagulation therapy is standard of care for patients with nonvalvular atrial fibrillation to prevent stroke. This study compared rivaroxaban and warfarin for stroke and all-cause mortality risk reduction in a real-world setting. Methods— This retrospective cohort study (2011–2017) included de-identified patients from the Optum Clinformatics Database who started treatment with rivaroxaban or warfarin within 30 days following initial diagnosis of nonvalvular atrial fibrillation. Before nonvalvular atrial fibrillation diagnosis, patients had 6 months of continuous health plan enrollment and CHA 2 DS 2 -VASc score ≥2. Stroke severity was determined by the National Institutes of Health Stroke Scale, imputed based on machine learning algorithms. Stroke and all-cause mortality risks were compared by treatment using Cox proportional hazard regression, with inverse probability of treatment weighting to balance cohorts for baseline risk factors. Stratified analysis by treatment duration was also performed. Results— During a mean follow-up of 27 months, 175 (1.33/100 patient-years [PY]) rivaroxaban-treated and 536 (1.66/100 PY) warfarin-treated patients developed stroke. The inverse probability of treatment weighting model showed that rivaroxaban reduced stroke risk by 19% (hazard ratio [HR], 0.81 [95% CI, 0.73–0.91]). Analysis by stroke severity revealed risk reductions by rivaroxaban of 48% for severe stroke (National Institutes of Health Stroke Scale score, 16–42; HR, 0.52 [95% CI, 0.33–0.82]) and 19% for minor stroke (National Institutes of Health Stroke Scale score, 1 to <5; HR, 0.81 [95% CI, 0.68–0.96]), but no difference for moderate stroke (National Institutes of Health Stroke Scale score, 5 to <16; HR, 0.93 [95% CI, 0.78–1.10]). A total of 41 (0.31/100 PY) rivaroxaban-treated and 147 (0.44/100 PY) warfarin-treated patients died poststroke, 12 (0.09/100 PY) and 67 (0.20/100 PY) of whom died within 30 days, representing mortality risk reductions by rivaroxaban of 24% (HR, 0.76 [95% CI, 0.61–0.95]) poststroke and 59% (HR, 0.41 [95% CI, 0.28–0.60]) within 30 days. Conclusions— After the initial diagnosis of atrial fibrillation, patients treated with rivaroxaban versus warfarin had significant risk reduction for stroke, especially severe stroke, and all-cause mortality after a stroke. Findings from this observational study may help inform anticoagulant choice for stroke prevention in patients with nonvalvular atrial fibrillation.