Which is best for patients with stable cardiovascular disease: aspirin, rivaroxaban, or both? The combination may be more beneficial for secondary prevention — but could carry an increased bleeding risk, according to a new study. Researchers randomized more than 27,000 patients with stable atherosclerotic vascular disease to rivaroxaban (2.5 mg twice a day) plus aspirin (100 mg daily), rivaroxaban alone, or aspirin alone with the primary outcome a composite of cardiovascular death, stroke, or myocardial infarction (secondary prevention). The study was ended early (after 23 months) when researchers noted the superiority of rivaroxaban plus aspirin. The primary outcome occurred less frequently in the rivaroxaban-plus-aspirin group compared to the aspirin alone group (4.1% vs. 5.4%; hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.66-0.86; P < 0.001), but major bleeding was more common in the combination group (3.1% vs. 1.9%; HR, 1.70; 95% CI, 1.40-2.05; P < 0.001). There was no significant difference in intracranial or fatal bleeding between these two groups. The death rate was lower in the rivaroxaban plus aspirin group (3.4% vs. 4.1%; HR, 0.82; 95% CI, 0.71-0.96; P = 0.01; threshold P value for significance, 0.0025). Rivaroxaban alone was no better than aspirin alone but was associated with more major bleeding events. The authors concluded that among patients with stable cardiovascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin experienced better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban alone was no better than aspirin. (N Engl J Med 2017; 377:1319-1330)