When is it indicated to use aspirin and Xarelto (Rivaroxaban) together?

Indications for Combined Use of Aspirin and Rivaroxaban (Xarelto)

The combination of aspirin and rivaroxaban is primarily indicated for patients with stable coronary artery disease (CAD) and/or peripheral artery disease (PAD) at high risk of ischemic events, using rivaroxaban at the specific vascular dose of 2.5 mg twice daily with aspirin 75-100 mg once daily. This dual pathway inhibition strategy targets both platelet aggregation and coagulation pathways.

Primary Indications for Combination Therapy

1. Coronary Artery Disease

• Patients with stable coronary artery disease at high risk of recurrent events 1
• Specifically approved to reduce the risk of major cardiovascular events (cardiovascular death, myocardial infarction, and stroke) 1
• The combination showed a 24% reduction in cardiovascular death, stroke, or myocardial infarction compared to aspirin alone 2

2. Peripheral Artery Disease

• Patients with symptomatic PAD, including those who have recently undergone lower extremity revascularization 1
• Indicated to reduce the risk of major thrombotic vascular events (myocardial infarction, ischemic stroke, acute limb ischemia, and major amputation) 1
• Particularly beneficial for patients after lower-extremity revascularization procedures 2

Important Dosing Considerations

• Rivaroxaban dose: 2.5 mg twice daily (vascular dose) - this is significantly lower than the dose used for atrial fibrillation (20 mg daily) 1
• Aspirin dose: 75-100 mg once daily 1
• This specific dosing regimen was established in the COMPASS trial and is critical for balancing efficacy and bleeding risk 3

NOT Indicated for Atrial Fibrillation

• For patients with atrial fibrillation, adding antiplatelet treatment to anticoagulation is NOT recommended to prevent recurrent embolic stroke 3
• The ESC guidelines explicitly state that combining antiplatelet drugs with anticoagulants should only occur in selected patients with acute vascular disease 3
• In AF patients, antiplatelet drugs should not be used for stroke prevention and can lead to potential harm 3

Time-Limited Indications in Acute Coronary Syndrome/PCI

For patients with atrial fibrillation who undergo PCI or develop ACS, combination therapy may be indicated but should be time-limited:

• Triple therapy (aspirin, clopidogrel, and anticoagulant) should be considered for 1 month after coronary stent implantation 3
• For patients with high ischemic risk due to ACS or other anatomical/procedural characteristics, triple therapy may be extended up to 6 months 3
• After this period, dual therapy with clopidogrel and anticoagulant should be considered 3
• Discontinuation of antiplatelet treatment should be considered at 12 months in patients treated with OAC 3

Clinical Benefits of Dual Pathway Inhibition

• Significant reduction in cardioembolic strokes and embolic strokes of undetermined source 4
• Reduction in major adverse cardiovascular events (MACE) and major adverse limb events (MALE) 5
• Reduction in all-cause and cardiovascular mortality with rivaroxaban 2.5 mg twice daily 6

Important Safety Considerations

• Increased risk of major bleeding compared to aspirin alone 5
• Increased risk of intracranial hemorrhage, though no increase in fatal bleeding 6
• The combination with ticagrelor or prasugrel has not been evaluated and is not recommended 3
• When rivaroxaban is used with aspirin, consider adding a proton pump inhibitor for gastric protection 7

Algorithm for Patient Selection

1. Assess if patient has established CAD or PAD

   • If yes, continue evaluation
   • If no, combination therapy is not indicated

2. Evaluate for contraindications:

   • High bleeding risk
   • Concurrent use of other anticoagulants
   • Severe renal impairment (CrCl <15 mL/min)

3. Determine specific indication:

   • Stable CAD (>12 months from ACS/PCI) at high risk of recurrent events
   • Symptomatic PAD, especially after revascularization
   • Recent ACS (<12 months) with need for extended protection

4. Prescribe appropriate dosing:

   • Rivaroxaban 2.5 mg twice daily
   • Aspirin 75-100 mg once daily

5. Monitor for bleeding complications and reassess benefit-risk periodically

Conclusion

The combination of aspirin and rivaroxaban at the specific vascular dose (2.5 mg twice daily) provides dual pathway inhibition that offers superior protection against major cardiovascular and limb events in patients with established CAD or PAD compared to aspirin alone, but at the cost of increased bleeding risk. This combination should not be used for stroke prevention in atrial fibrillation patients without CAD/PAD, and when used in patients with AF who have CAD/PAD, the duration of combination therapy should be limited based on the clinical scenario.