Should I continue Xarelto (rivaroxaban) and aspirin in a patient with a history of stroke?

Management of Antithrombotic Therapy After Stroke

The combination of Xarelto (rivaroxaban) and aspirin should not be continued in a patient with a history of stroke due to increased bleeding risk without proven additional benefit for secondary stroke prevention.

Antiplatelet Therapy for Secondary Stroke Prevention

Single vs. Dual Antiplatelet Therapy

For patients with a history of noncardioembolic ischemic stroke, the evidence strongly favors single antiplatelet therapy for long-term secondary prevention:

• The MATCH trial demonstrated that the combination of clopidogrel plus aspirin significantly increased the risk of major hemorrhage compared to clopidogrel alone, with a 1.3% absolute increase in life-threatening bleeding, without providing significant benefit in reducing recurrent stroke 1.

• According to AHA/ASA guidelines, "the addition of aspirin to clopidogrel increases the risk of hemorrhage and is not routinely recommended for ischemic stroke or TIA patients" (Class III, Level of Evidence A) 1.

• The CHARISMA trial showed no significant benefit of combination therapy with clopidogrel plus aspirin compared to aspirin alone in reducing stroke recurrence, but did show increased bleeding risk 1.

Recommended Antiplatelet Options

For long-term secondary stroke prevention, the following single antiplatelet options are recommended:

1. Aspirin (50-325 mg daily)
2. Clopidogrel (75 mg daily)
3. Combination of aspirin (25 mg) and extended-release dipyridamole (200 mg twice daily)

The selection should be based on patient-specific factors including:

• Comorbidities
• Risk of bleeding
• Drug interactions
• Cost considerations
• Patient tolerance 1, 2

Special Considerations for Rivaroxaban (Xarelto)

Rivaroxaban in Stroke Prevention

• The NAVIGATE ESUS trial specifically evaluated rivaroxaban versus aspirin for prevention of recurrent stroke and found that rivaroxaban was not superior to aspirin for prevention of recurrent stroke after embolic stroke of undetermined source 3.

• More concerning, rivaroxaban was associated with a significantly higher risk of bleeding compared to aspirin (annualized rate 1.8% vs 0.7%, hazard ratio 2.72) 3.

• There is no evidence supporting the combination of rivaroxaban and aspirin specifically for secondary stroke prevention in patients with a history of stroke.

Management Algorithm for Patients on Xarelto and Aspirin

1. Determine stroke etiology:

   • If cardioembolic (e.g., atrial fibrillation): Consider anticoagulation alone
   • If non-cardioembolic: Transition to single antiplatelet therapy

2. For non-cardioembolic stroke:

   • Discontinue rivaroxaban
   • Continue aspirin 81-100 mg daily OR
   • Switch to clopidogrel 75 mg daily OR
   • Switch to aspirin 25 mg plus extended-release dipyridamole 200 mg twice daily

3. For cardioembolic stroke:

   • Continue rivaroxaban alone (discontinue aspirin)
   • Consider alternative anticoagulants if indicated

Pitfalls and Caveats

• Bleeding risk: The combination of any anticoagulant with antiplatelet therapy significantly increases bleeding risk without proportional benefit in stroke prevention 1.

• Transitioning between therapies: When switching from dual therapy to single therapy, there is no need for a washout period; simply discontinue one agent.

• Patient education: Emphasize the importance of adherence to the chosen antithrombotic regimen, as missed doses of short-acting agents like rivaroxaban can lead to periods of inadequate protection.

• Special populations: For patients with mechanical heart valves, warfarin remains the anticoagulant of choice rather than rivaroxaban 1.

• Monitoring: Regular follow-up is essential to assess for any bleeding complications or signs of recurrent stroke.

By following these evidence-based recommendations, you can optimize the balance between stroke prevention and bleeding risk for your patient with a history of stroke.