- Question
- Is adding low-dose rivaroxaban to aspirin, or rivaroxaban alone, more effective than aspirin alone for secondary cardiovascular prevention in patients with stable atherosclerotic disease?
- Design
- Randomized, double-blind, phase 3, three-arm trial with 27395 participants. It was stopped early for superiority of the combination, with a mean follow-up of 23 months.
- Population
- Patients with stable atherosclerotic vascular disease (coronary or peripheral artery disease).
- Intervention
- Rivaroxaban 2.5 mg twice daily plus aspirin 100 mg once daily, or rivaroxaban 5 mg twice daily alone (with aspirin placebo).
- Control
- Aspirin 100 mg once daily plus rivaroxaban placebo.
- Primary outcome
- Composite of cardiovascular death, stroke, or myocardial infarction; the primary safety outcome was major bleeding by modified ISTH criteria.
- Results
- The primary outcome occurred in 379 patients (4.1%) with rivaroxaban plus aspirin vs. 496 (5.4%) with aspirin alone (HR 0.76; 95% CI 0.66 to 0.86; P<0.001). All-cause death occurred in 313 (3.4%) vs. 378 (4.1%) (HR 0.82; 95% CI 0.71 to 0.96; P=0.01, which did not meet the significance threshold of 0.0025). Rivaroxaban alone did not significantly reduce the primary outcome compared with aspirin alone.
- Safety
- Major bleeding was more frequent with rivaroxaban plus aspirin: 288 patients (3.1%) vs. 170 (1.9%) (HR 1.70; 95% CI 1.40 to 2.05; P<0.001), with no significant difference in intracranial or fatal bleeding. Rivaroxaban alone also increased major bleeding.
- Conclusion
- In stable atherosclerotic disease, rivaroxaban 2.5 mg twice daily plus aspirin improved cardiovascular outcomes at the cost of more major bleeding, whereas rivaroxaban 5 mg alone was not better than aspirin.
- Why it matters
- It introduced dual-pathway inhibition (low-dose anticoagulant plus antiplatelet) as a secondary prevention option in selected patients, requiring a balance between ischemic benefit and bleeding risk.
Card generated automatically with AI from the abstract of the original publication and the trial registry; every figure was checked against those sources. It may contain errors: verify the data at the source before using it for clinical decisions.
Generated on October 7, 2026