Rivaroxaban is FDA-Approved for Cardiovascular Risk Reduction with Aspirin
Rivaroxaban (Answer B) is the only anticoagulant among the options that is FDA-approved to reduce the risk of major cardiovascular events when given in combination with aspirin. 1
FDA-Approved Indication
Rivaroxaban 2.5 mg twice daily combined with aspirin (75-100 mg once daily) is specifically indicated to reduce the risk of major cardiovascular events (cardiovascular death, myocardial infarction, and stroke) in patients with coronary artery disease (CAD) and to reduce major thrombotic vascular events in patients with peripheral artery disease (PAD). 1
Evidence Supporting This Approval
The COMPASS trial (27,395 patients with stable atherosclerotic vascular disease) demonstrated that rivaroxaban 2.5 mg twice daily plus aspirin 100 mg daily was superior to aspirin alone, with: 2, 3
- 24% relative risk reduction in major adverse cardiovascular events (4.1% vs 5.4%; HR 0.76,95% CI 0.66-0.86, p<0.001) 3
- 18% reduction in all-cause mortality (3.4% vs 4.1%; HR 0.82,95% CI 0.71-0.96) 3, 4
- 22% reduction in cardiovascular death (HR 0.78,95% CI 0.64-0.96) 4
The absolute benefits were particularly pronounced in high-risk subgroups including patients with diabetes, polyvascular disease, heart failure, and chronic kidney disease. 2
Why the Other Options Are Incorrect
Warfarin (Answer A): While warfarin combined with aspirin has been studied in atrial fibrillation, it is not approved for reducing cardiovascular events in stable coronary or peripheral artery disease and significantly increases bleeding risk when combined with antiplatelet therapy. 2, 5
Apixaban (Answer C): Apixaban is approved for stroke prevention in atrial fibrillation and VTE treatment, but has no FDA indication for reducing cardiovascular events in combination with aspirin in stable atherosclerotic disease. 2
Fondaparinux (Answer D): Fondaparinux is approved for VTE prophylaxis and treatment of acute coronary syndromes, but not for chronic cardiovascular risk reduction with aspirin. 2
Clinical Implementation Considerations
The combination therapy increases major bleeding risk (3.1% vs 1.9%; HR 1.70,95% CI 1.40-2.05), primarily gastrointestinal bleeding, but does not significantly increase intracranial or fatal bleeding. 2, 3
Patient selection is critical: The 2024 ESC guidelines recommend this combination for high ischemic risk patients without high bleeding risk, particularly those with diabetes, PAD, mild chronic kidney disease, or active smoking. 2
The rivaroxaban 5 mg twice daily monotherapy regimen (without aspirin) did NOT show significant benefit over aspirin alone and is not recommended for this indication. 3, 6