Can Eliquis (apixaban) and Plavix (clopidogrel) be given together?

Eliquis and Plavix Combination Therapy

Eliquis (apixaban) and Plavix (clopidogrel) can be given together in specific clinical scenarios, but this combination significantly increases bleeding risk and should only be used when the ischemic benefit clearly outweighs this risk.

Clinical Scenarios Where Combination Therapy Is Used

1. Atrial Fibrillation with Acute Coronary Syndrome or PCI

• In patients with atrial fibrillation who undergo PCI or have ACS, a period of dual antithrombotic therapy (DAT) with Eliquis and a P2Y12 inhibitor (like Plavix) is recommended 1:
  • Preferred over triple therapy (OAC + DAPT) due to lower bleeding risk
  • Typically used for at least 6 months in medically managed NSTE-ACS patients

2. Recommended Dosing When Combined

• When Eliquis is combined with Plavix, the recommended dose is 1:
  • Apixaban 5 mg twice daily (standard dose)
  • Dose reduction to 2.5 mg twice daily for patients with:
    • Renal impairment
    • Age ≥80 years
    • Body weight ≤60 kg
    • High bleeding risk

Evidence Supporting This Approach

The 2021 ESC guidelines for NSTE-ACS management support the use of dual therapy with a NOAC (like apixaban) and a P2Y12 inhibitor (like clopidogrel) 1. The AUGUSTUS trial demonstrated that apixaban significantly reduced bleeding events compared to vitamin K antagonists when combined with a P2Y12 inhibitor (HR 0.44,95% CI 0.28-0.68) 1.

Important Considerations and Risks

Bleeding Risk

• The combination significantly increases bleeding risk compared to either agent alone 2
• In the APPRAISE-2 trial, apixaban plus antiplatelet therapy increased Thrombolysis In Myocardial Infarction (TIMI) major bleeding:
  • With aspirin alone: HR 6.62 (95% CI: 0.75 to 51.73)
  • With aspirin plus clopidogrel: HR 2.44 (95% CI: 1.34 to 4.45) 2

Duration of Therapy

• For most patients, the duration of combination therapy should be minimized to reduce bleeding risk
• After PCI in patients with AF, the 2018 EHRA guide suggests 1:
  • Dual therapy (NOAC + P2Y12 inhibitor, mainly clopidogrel) is safer than triple therapy
  • Duration typically ranges from 1-12 months depending on thrombotic and bleeding risks

Proton Pump Inhibitors

• Proton pump inhibitors should be prescribed when combining antiplatelet and anticoagulant therapy to reduce GI bleeding risk 1
• Note: While omeprazole and esomeprazole may reduce clopidogrel's active metabolite exposure, their clinical impact on ischemic events remains uncertain 1

Alternative Approaches

1. For patients with very high bleeding risk:

   • Consider shortening the duration of dual therapy
   • Consider using clopidogrel rather than more potent P2Y12 inhibitors (ticagrelor/prasugrel)

2. For chronic coronary syndrome patients without AF:

   • Single antiplatelet therapy is generally preferred over combination with anticoagulants 1

Common Pitfalls to Avoid

1. Unnecessary triple therapy: Adding aspirin to Eliquis and Plavix (triple therapy) significantly increases bleeding without clear evidence of improved efficacy in most patients 1

2. Inappropriate dosing: Failing to adjust Eliquis dose based on renal function, age, and weight when combining with antiplatelet therapy

3. Inadequate GI protection: Not prescribing proton pump inhibitors in patients receiving combination therapy

4. Prolonged combination therapy: Extending dual therapy beyond necessary duration increases cumulative bleeding risk without additional benefit

In conclusion, while Eliquis and Plavix can be given together in specific clinical scenarios (primarily AF with recent ACS or PCI), this combination requires careful consideration of bleeding versus thrombotic risks, appropriate dosing, and measures to mitigate bleeding complications.