Effectiveness and Safety of Rivaroxaban Versus Warfarin among Nonvalvular Atrial Fibrillation Patients with Concomitant Obstructive Sleep Apnea

Abstract

Background: Obstructive sleep apnea (OSA) is associated with an increased incidence of atrial fibrillation (AF), hypertension, diabetes, heart failure, coronary heart disease, stroke, and death. We sought to evaluate the effectiveness and safety of rivaroxaban versus warfarin in nonvalvular AF (NVAF) patients with concomitant OSA. Methods: This was an analysis of electronic health record (EHR) data from 11/2010–12/2021. We included adults with NVAF and OSA at baseline, newly initiated on rivaroxaban or warfarin and with ≥12-months of prior EHR activity. Patients with valvular disease, alternative indications for oral anticoagulation, or who were pregnant were excluded. The incidence rates of developing stroke or systemic embolism (SSE) and bleeding-related hospitalization were evaluated. Hazard ratios (HR) and 95% confidence intervals (CIs) were calculated using propensity score-overlap weighted proportional hazards regression. Multiple sensitivity and subgroup analyses were performed. Results: We included 21,940 rivaroxaban (20.1% at the 15 mg dose) and 38,213 warfarin (time-in-therapeutic range=47.3±28.3%) patients. Rivaroxaban was found to have similar hazard of SSE compared to warfarin (HR=0.92, 95%CI=0.82–1.03). Rivaroxaban was associated with a reduced rate of bleeding-related hospitalizations (HR=0.85, 95%CI=0.78–0.92) versus warfarin, as well as reductions in intracranial (HR=0.76, 95%CI=0.62–0.94) and extracranial (HR=0.89, 95%CI=0.81–0.97) bleeding. Upon sensitivity analysis restricting the population to men with a CHA2DS2VASC score ≥2 or women with a score ≥3, rivaroxaban was associated with significant 33% risk reductions in SSE and 43% reduction in the risk of bleeding-related hospitalization. No significant interaction for the SSE or bleeding-related hospitalization outcomes were observed upon subgroup analyses. Conclusions: Among patients with NVAF and OSA, rivaroxaban had similar SSE risk versus warfarin but was associated with reductions in any, intracranial, and extracranial bleeding-related hospitalizations. Rivaroxaban was associated with significant reductions in SSE and bleeding-related hospitalizations when the study population was restricted to patients with a moderate-to-high risk of SSE. These data should provide prescribers with additional confidence in selecting rivaroxaban in NVAF patients who have OSA at time of anticoagulation initiation.