What are alternative antithrombotic options for a patient on clopidogrel (Plavix) and apixaban (Eliquis)?

Alternative Antithrombotic Options for Patients on Clopidogrel and Apixaban

For patients currently on dual therapy with clopidogrel and apixaban, the recommended alternative is to discontinue one agent (typically clopidogrel) and continue with apixaban monotherapy, as this provides the best balance of thrombotic protection and bleeding risk. 1

Current Combination Assessment

The combination of clopidogrel and apixaban (dual antithrombotic therapy) is typically used in specific clinical scenarios:

• Patients with atrial fibrillation who have undergone recent PCI
• Patients with venous thromboembolism and coronary artery disease
• Patients with high thrombotic risk requiring both antiplatelet and anticoagulant protection

This combination significantly increases bleeding risk compared to either agent alone, necessitating careful consideration of alternative approaches.

Alternative Options Based on Clinical Context

Option 1: Discontinue Clopidogrel, Continue Apixaban Monotherapy

• Best for: Patients >12 months post-PCI or with atrial fibrillation as primary indication
• Evidence: After 12 months post-PCI, antiplatelet therapy can be discontinued in patients treated with oral anticoagulants 1
• Advantage: Significantly reduces bleeding risk while maintaining stroke prevention

Option 2: Switch to Rivaroxaban-Based Regimen

• Alternative 1: Rivaroxaban 15 mg daily + clopidogrel

  • Supported by guidelines when combination therapy is required 1
  • Rivaroxaban 15 mg daily may be used instead of 20 mg when combined with antiplatelet therapy

• Alternative 2: Rivaroxaban 2.5 mg twice daily + aspirin (for CAD/PAD patients)

  • Based on COMPASS trial data for patients with stable atherosclerotic disease 1
  • NNT: 77 for ischemic outcomes; NNH: 84 for bleeding outcomes

Option 3: Time-Limited Triple Therapy

• For very high thrombotic risk patients only: Apixaban + clopidogrel + aspirin
• Duration: Limited to 1 month maximum 1
• Caution: Triple therapy significantly increases bleeding risk and should be minimized

Option 4: Alternative P2Y12 Inhibitor with Apixaban

• Not recommended: Ticagrelor or prasugrel with apixaban
• Guidelines explicitly recommend against using these more potent P2Y12 inhibitors as part of combination therapy with anticoagulants 1

Dosing Considerations for Combination Therapy

If combination therapy must be continued:

• Use the lowest approved dose of apixaban effective for stroke prevention (2.5 mg twice daily may be considered in appropriate patients) 1
• Maintain clopidogrel at standard dose of 75 mg daily 2
• Avoid adding aspirin unless absolutely necessary for very high thrombotic risk

Decision Algorithm Based on Clinical Scenario

1. If >12 months post-PCI or stent placement:

   • Discontinue clopidogrel
   • Continue apixaban monotherapy (standard dose)

2. If <12 months post-PCI but >1 month:

   • Continue dual therapy with apixaban + clopidogrel
   • Consider dose reduction of apixaban if bleeding risk is high

3. If <1 month post-PCI with high thrombotic risk:

   • Consider short-term triple therapy (apixaban + clopidogrel + aspirin)
   • Limit triple therapy to shortest duration possible (≤30 days)

4. If patient has stable CAD without recent intervention:

   • Consider switching to rivaroxaban 2.5 mg twice daily + aspirin 100 mg daily

Important Considerations

• Bleeding risk monitoring: All combination therapies increase bleeding risk compared to monotherapy 3, 4
• Proton pump inhibitors: Should be considered for patients on dual or triple therapy to reduce GI bleeding risk 5
• Regular reassessment: Reevaluate the need for combination therapy at each visit
• Drug interactions: Monitor for potential interactions between antiplatelet and anticoagulant medications 2, 6

Remember that the duration of combination therapy should be minimized whenever possible, with a clear plan to transition to monotherapy when clinically appropriate.