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Background: Growing evidence suggests that obstructive sleep apnea (OSA) is associated with an increased risk of stroke and adverse cardiovascular outcomes; however, there are limited data that treating OSA with positive airway pressure (PAP) devices significantly decreases this risk. We therefore examined the association between PAP therapy and the risk of subsequent stroke and cardiovascular outcomes in patients with OSA.Methods: We performed a population-based cohort study using outpatient and inpatient administrative claims data from a nationally representative 5% sample of Medicare beneficiaries from 2008 through 2014. Our cohort comprised patients with OSA, whom we identified using an algorithm of an ICD-9-CM procedure code for a home or lab sleep study along with at least two subsequent diagnostic code claims for OSA. Our predictor variable was prescribed therapy with continuous PAP or bi-level PAP, defined using CPT codes. Our primary outcome was a composite of hospitalization for ischemic stroke, hemorrhagic stroke (intracerebral or subarachnoid hemorrhage), myocardial infarction, or congestive heart failure. Kaplan-Meier survival statistics were used to calculate cumulative rates, and Cox regression analysis was used to calculate hazard ratios (HR) that adjusted for age, sex, race, and established vascular risk factors.Results: We identified 38,987 patients with OSA, of whom 1,195 were prescribed PAP therapy. The mean age of all patients with OSA was 73.0 (±5.5) years, and 43.6% were women. Patients prescribed PAP therapy had a higher baseline burden of vascular comorbidities. The mean follow-up was 2.2 (±1.6) years. By 5 years of follow-up, the cumulative rate of our composite outcome was 30.3% (95% CI, 25.4-35.9%) in patients prescribed PAP therapy versus 31.2% (95% CI, 30.4-32.0%) in untreated patients (adjusted HR, 0.8; 95% CI, 0.7-0.9). This association was similar but not statistically significant when assessing the secondary outcome of ischemic or hemorrhagic stroke (adjusted HR, 0.7; 95% CI, 0.5-1.1).Conclusion: Patients with OSA who were treated with PAP were less likely to experience stroke or adverse cardiovascular events compared to those who did not receive treatment.