AIMS:The aim of this study was to evaluate the effects of apixaban, a novel oral factor Xa inhibitor, on the need for cardiovascular hospitalization. METHODS AND RESULTS:Our analysis is based on data from AVERROES, a randomized double-blind trial testing the efficacy and safety of apixaban against aspirin for the prevention of thrombo-embolism in 5599 atrial fibrillation (AF) patients unsuitable for vitamin K antagonist therapy. Hospitalizations were captured by dedicated case report forms and the outcome variable was time from randomization to the first hospitalization. Effects of treatment with apixaban on the rates of cardiovascular and non-cardiovascular hospitalizations were assessed using Cox proportional hazards regression models. During a mean follow-up of 1.1 years, 800 patients were hospitalized at least once for cardiovascular reasons, 442 (15.4%/year) in the aspirin group, 358 (12.3%) in the apixaban group [hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.69-0.92; P = 0.002]. The reduction in cardiovascular hospitalization in the apixaban arm was predominantly due to a reduction in hospitalization for strokes, but there were also fewer hospitalizations for other cardiovascular causes. Patients with paroxysmal AF were significantly more likely to be hospitalized for AF treatment, whereas more heart failure admissions occurred in patients with permanent AF. Assignment to apixaban was the only independent predictor for a reduction in hospitalization. Cardiovascular hospitalization was the strongest independent predictor of subsequent mortality (HR: 3.95, 95% CI: 3.06-5.09; P < 0.001). CONCLUSION:In AVERROES, patients on apixaban therapy were less likely to be hospitalized. This may have important consequences for patients' well-being and for healthcare resources. This trial is registered underClinicalTrials.gov number, NCT00496769.