When should a patient with acute coronary syndrome and atrial fibrillation be on both Clopidogrel (Plavix) and Eliquis (Apixaban)?

When to Use Both Clopidogrel and Eliquis (Apixaban)

Patients with atrial fibrillation who undergo percutaneous coronary intervention (PCI) for acute coronary syndrome should receive dual antithrombotic therapy with apixaban and clopidogrel as the default strategy after a brief initial period of triple therapy (aspirin, clopidogrel, and apixaban) lasting no more than 1 week to 1 month. 1, 2

Primary Clinical Indication

The combination of clopidogrel and apixaban is specifically indicated for patients who have both conditions requiring treatment:

• Atrial fibrillation requiring anticoagulation for stroke prevention AND
• Recent acute coronary syndrome (ACS) or PCI with stent placement 1, 2

This dual therapy approach has been validated in multiple randomized trials demonstrating either noninferiority or no significant difference for ischemic endpoints but superior safety compared with triple antithrombotic therapy. 1

Initial Triple Therapy Period (Aspirin + Clopidogrel + Apixaban)

Duration should be minimized to reduce bleeding risk:

• Standard approach: Triple therapy for up to 1 week after the acute event, then discontinue aspirin 2

• High ischemic risk patients: May extend triple therapy up to 1 month (exceptionally up to 6 months) for patients with:

  • Prior stent thrombosis on adequate antiplatelet therapy
  • Stenting of the last remaining patent coronary artery
  • Diffuse multivessel disease, especially in diabetic patients
  • At least three stents implanted or three lesions treated
  • Bifurcation with two stents implanted
  • Total stented length >60 mm
  • Treatment of chronic total occlusion
  • History of STEMI 1, 2

• Low bleeding risk with very high thrombotic risk: Triple therapy may be considered for up to 30 days following PCI 1

Dual Therapy Period (Clopidogrel + Apixaban)

After discontinuing aspirin, continue dual therapy:

• Duration: Up to 12 months for ACS patients 1, 2, 3
• Stable coronary artery disease post-PCI: 1-6 months may be sufficient 2
• After 12 months: Discontinue clopidogrel and continue apixaban monotherapy for stroke prevention 2

Specific Dosing Recommendations

Apixaban dosing:

• Standard dose: 5 mg twice daily 1, 2
• Reduced dose: 2.5 mg twice daily if patient meets at least 2 of the following criteria:
  • Age ≥80 years
  • Body weight ≤60 kg
  • Serum creatinine ≥1.5 mg/dL (133 μmol/L) 1, 2

Clopidogrel dosing:

• Standard dose: 75 mg daily 1, 2
• Clopidogrel is strongly preferred over prasugrel or ticagrelor when combined with anticoagulation due to lower bleeding risk 1, 2

Aspirin dosing (when used in triple therapy):

• Maximum dose: 100 mg daily 1, 2
• Should be discontinued as early as possible (within 1 week preferred) 2

Mandatory Bleeding Risk Mitigation

All patients on this combination therapy require:

• Proton pump inhibitor (PPI) prophylaxis is mandatory to reduce gastrointestinal bleeding 2, 4
• Pantoprazole 40 mg daily is preferred due to minimal interaction with clopidogrel 4
• Omeprazole and esomeprazole should be avoided due to CYP2C19 inhibition concerns 4

Patients Who Should NOT Receive This Combination

Avoid dual therapy in patients with:

• High bleeding risk that outweighs ischemic risk:
  • Prior major bleeding or hemorrhagic stroke 1
  • Active bleeding 4
  • Severe chronic kidney disease (creatinine clearance <30 mL/min) 1
  • Advanced age with frailty 1
  • Ongoing malignancy 1
  • Chronic alcohol abuse 1
  • Clinically significant anemia 1

For high bleeding risk patients: Consider clopidogrel alone with apixaban, potentially shortening dual therapy duration to as little as 1 month in selected patients with low risk of stent thrombosis. 2

Critical Pitfalls to Avoid

• Never continue triple therapy beyond what is absolutely necessary (ideally ≤1 week, maximum 1 month for most patients), as extended triple therapy significantly increases bleeding without proportional reduction in thrombotic events 2

• Never use ticagrelor or prasugrel as part of combination therapy with anticoagulation, as these more potent P2Y12 inhibitors substantially increase bleeding risk 1, 2

• Never forget to discontinue clopidogrel at 12 months after ACS/PCI, as thrombotic risk decreases over time while bleeding risk persists with continued dual therapy 2

• Never use this combination in atrial fibrillation patients without recent ACS or PCI, as apixaban monotherapy is preferred for stroke prevention in atrial fibrillation without coronary disease 2

Medically Managed ACS (No PCI)

For atrial fibrillation patients with ACS managed medically (without PCI):

• Consider adding clopidogrel 75 mg daily to apixaban for up to 1 year 2
• This represents a weaker recommendation with less robust evidence than the post-PCI scenario 2

Transition to Long-Term Therapy

After completing 12 months of dual therapy:

• Discontinue clopidogrel 2
• Continue apixaban monotherapy indefinitely for stroke prevention in atrial fibrillation 2
• Regular reassessment of bleeding and thrombotic risk is essential 1