Can I prescribe Eliquis (apixaban) and clopidogrel at the same time?

Concomitant Use of Eliquis (Apixaban) and Clopidogrel

Eliquis (apixaban) and clopidogrel can be prescribed together, but this combination significantly increases bleeding risk and should be limited to specific clinical scenarios with careful risk assessment.

Indications for Combination Therapy

The combination of apixaban and clopidogrel is primarily indicated in the following clinical scenarios:

• Atrial fibrillation with recent acute coronary syndrome (ACS) or coronary stent placement 1
• Mechanical heart valves with coronary stenting 1
• High thrombotic risk conditions requiring both anticoagulation and antiplatelet therapy 1

Risk Assessment and Duration of Therapy

When considering this combination, carefully assess:

1. Bleeding risk using validated scores like HAS-BLED
2. Thrombotic risk based on indication for each medication
3. Time since coronary intervention (if applicable)

Duration Recommendations:

• Acute coronary syndrome with AF requiring anticoagulation:

  • After a short period of triple therapy (OAC + aspirin + clopidogrel) for up to 1 week, dual therapy with apixaban and clopidogrel is recommended as the default strategy 1
  • Continue dual therapy for up to 12 months, then discontinue antiplatelet therapy 1

• Stable coronary artery disease with AF:

  • Discontinue antiplatelet medications after 12 months in patients treated with an oral anticoagulant 1

Dosing Considerations

• Standard apixaban dosing (5mg twice daily) may need adjustment:
  • Consider reduced dose (2.5mg twice daily) in patients with ≥2 of: age ≥80 years, weight ≤60kg, or serum creatinine ≥1.5mg/dL
  • When rivaroxaban is used with antiplatelet therapy in patients with high bleeding risk, a reduced dose (15mg daily) should be considered instead of 20mg daily 1

Bleeding Risk Management

The combination of apixaban and clopidogrel significantly increases bleeding risk:

• Mandatory prophylactic measures:

  • Prescribe a proton pump inhibitor (PPI) to reduce GI bleeding risk 1
  • Consider pantoprazole as the preferred PPI as it has less interaction with clopidogrel metabolism compared to omeprazole 1

• Monitoring recommendations:

  • Regular assessment for bleeding signs (bruising, melena, hematuria)
  • Periodic hemoglobin/hematocrit monitoring
  • Patient education about bleeding symptoms requiring medical attention

Common Pitfalls and Caveats

1. Avoid triple therapy (aspirin + clopidogrel + apixaban) beyond 1 week unless absolutely necessary due to substantially increased bleeding risk 1

2. Do not use ticagrelor or prasugrel with apixaban as these more potent P2Y12 inhibitors further increase bleeding risk without proven benefit 1

3. Recognize that bleeding risk increases with duration of combination therapy - reassess the need for continued dual therapy regularly 1

4. Be aware that apixaban plus clopidogrel increases bleeding time significantly compared to either agent alone 2

5. Remember that post-ACS, apixaban added to antiplatelet therapy increases bleeding without improving efficacy in most scenarios 3

Alternative Approaches

In patients with extremely high bleeding risk but requiring both anticoagulation and antiplatelet therapy:

• Consider using clopidogrel alone (without aspirin) with apixaban 1
• For AF patients with coronary disease, consider discontinuing antiplatelet therapy earlier (after 6 months) if bleeding risk is very high 1

The evidence clearly demonstrates that while this combination can be prescribed, it requires careful patient selection, risk assessment, and bleeding risk mitigation strategies to ensure patient safety.