Can I combine aspirin and clopidogrel (Plavix) after a stroke?

Combining Aspirin and Clopidogrel After Stroke

The combination of aspirin and clopidogrel is not routinely recommended for long-term secondary prevention after ischemic stroke or TIA due to increased bleeding risk without significant benefit in reducing recurrent events. 1

Evidence Against Routine Combination Therapy

• The Management of Atherothrombosis with Clopidogrel in High-Risk Patients with TIA or Stroke (MATCH) trial showed no significant benefit of combination therapy (clopidogrel plus aspirin) compared to clopidogrel alone in reducing ischemic events 1
• The combination therapy significantly increased the risk of major hemorrhage with a 1.3% absolute increase in life-threatening bleeding compared to monotherapy 1
• American Heart Association/American Stroke Association guidelines explicitly state that "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

Appropriate Antiplatelet Options After Stroke

• For patients with noncardioembolic ischemic stroke or TIA, antiplatelet agents rather than oral anticoagulation are recommended (Class I, Level of Evidence A) 1
• Acceptable single-agent options include:
  • Aspirin (50-325 mg/day) 1
  • Clopidogrel (75 mg/day) 1
  • Combination of aspirin and extended-release dipyridamole 1

Special Circumstances Where Combination May Be Considered

• Recent acute coronary syndromes or after vascular stenting 1
• Acute minor stroke or high-risk TIA within 24 hours of symptom onset, where short-term dual antiplatelet therapy (21-90 days) may be beneficial 2
  • The CHANCE trial showed that in patients treated within 24 hours after minor stroke or TIA, the combination of clopidogrel and aspirin reduced stroke risk compared to aspirin alone (8.2% vs 11.7%) without increasing hemorrhage risk 2

Selecting the Appropriate Antiplatelet Therapy

• For most stroke patients, monotherapy with either aspirin, clopidogrel, or aspirin plus extended-release dipyridamole is recommended 1
• Clopidogrel is a reasonable alternative for patients allergic to aspirin (Class IIa, Level of Evidence B) 1
• The selection should be individualized based on:
  • Patient risk factor profile 1
  • Medication tolerance 1
  • Cost considerations (aspirin is significantly less expensive) 1

Important Considerations and Precautions

• Clopidogrel is a prodrug requiring conversion to an active metabolite through the CYP2C19 enzyme system 3
• Genetic variations in CYP2C19 or concurrent use of medications that inhibit CYP2C19 (like omeprazole or esomeprazole) can reduce clopidogrel's effectiveness 3
• Discontinuation of antiplatelet therapy increases cardiovascular event risk; if temporary discontinuation is necessary, resume as soon as possible 3

Conclusion

While combining aspirin and clopidogrel may be beneficial in specific acute settings (like recent minor stroke or TIA within 24 hours), the evidence strongly recommends against routine long-term combination therapy for secondary stroke prevention due to increased bleeding risk without demonstrated efficacy benefit 1.