Should a patient with atrial fibrillation on Eliquis (apixaban) also be prescribed Plavix (clopidogrel) for stroke prevention?

Should a Patient on Eliquis (Apixaban) Also Take Plavix (Clopidogrel)?

No, a patient with atrial fibrillation already on Eliquis (apixaban) should NOT be prescribed Plavix (clopidogrel) for stroke prevention. Adding clopidogrel to apixaban provides no additional stroke protection and significantly increases bleeding risk, particularly intracranial hemorrhage. 1, 2, 3

Why Antiplatelet Therapy Should Not Be Added

Apixaban alone is the definitive treatment for stroke prevention in atrial fibrillation. The evidence is unequivocal:

• Oral anticoagulation reduces stroke risk by 62%, while antiplatelet therapy provides only 22% risk reduction 2
• Adding clopidogrel to anticoagulation does not prevent recurrent embolic stroke and only increases bleeding risk 1, 2
• The American College of Chest Physicians strongly recommends against antiplatelet therapy (including clopidogrel) when oral anticoagulation is indicated for atrial fibrillation 2

The Only Exception: Recent Coronary Intervention

Clopidogrel should ONLY be combined with apixaban if the patient has recently undergone percutaneous coronary intervention (PCI) or experienced acute coronary syndrome (ACS). Even then, this combination must be strictly time-limited: 1, 3, 4

Triple Therapy Protocol (if applicable):

• Duration: 4-6 weeks maximum after PCI/ACS 1, 2
• Regimen: Apixaban 5 mg twice daily + clopidogrel 75 mg daily + aspirin 81 mg daily 1, 3
• Mandatory PPI prophylaxis (pantoprazole or lansoprazole, NOT omeprazole) to reduce GI bleeding 3

Transition to Double Therapy:

• After 4-6 weeks, discontinue aspirin and continue only apixaban + clopidogrel 1, 2
• Continue double therapy for up to 12 months post-ACS or 6 months for stable ischemic heart disease 3
• After this period, return to apixaban monotherapy 1, 2

Evidence Supporting Apixaban Monotherapy

Apixaban has proven superiority over warfarin and aspirin for stroke prevention:

• 21% relative risk reduction in stroke/systemic embolism vs. warfarin (HR 0.79,95% CI 0.66-0.95) 1, 2
• 51% reduction in hemorrhagic stroke (RR 0.49,95% CI 0.38-0.64) 2
• 52% reduction in intracranial hemorrhage (RR 0.48,95% CI 0.39-0.59) 2
• 10% reduction in all-cause mortality (RR 0.90,95% CI 0.85-0.95) 2

When compared to aspirin in the AVERROES trial, apixaban demonstrated a 55% relative risk reduction in stroke (HR 0.45,95% CI 0.32-0.62) without increasing major bleeding 1, 5

Critical Pitfalls to Avoid

Do not combine antiplatelet therapy with anticoagulation based on:

• "Extra protection" reasoning - this is incorrect and dangerous 1, 2
• History of coronary artery disease without recent intervention - apixaban alone is sufficient 1, 3
• Patient or physician anxiety about stroke risk - apixaban provides optimal protection 2

The combination of aspirin and clopidogrel has similar bleeding risk to warfarin but remains inferior for stroke prevention 1, 2, 6

When to Reassess

If the patient has stable coronary artery disease without recent ACS/PCI:

• Continue apixaban monotherapy 1, 2
• Optimize cardiovascular risk factors (blood pressure, lipids, diabetes control) 2
• Do NOT add antiplatelet therapy 1, 2

If the patient develops ACS or requires PCI in the future:

• Implement the time-limited triple/double therapy protocol described above 1, 3, 4
• Always return to apixaban monotherapy after the specified duration 1, 2