What is the lowest prescribed dose of clopidogrel and apixaban (Eliquis) combined?

Lowest Prescribed Dose of Clopidogrel and Apixaban Combined

The lowest prescribed dose combination is clopidogrel 75 mg daily plus apixaban 2.5 mg twice daily, specifically indicated for patients requiring dual therapy with an oral anticoagulant who meet dose-reduction criteria. 1

Dosing Framework for Combined Therapy

Standard Maintenance Dosing

• Clopidogrel 75 mg once daily is the established maintenance dose across all guidelines for patients requiring antiplatelet therapy 1, 2
• Apixaban 2.5 mg twice daily is the reduced dose approved for stroke prevention in atrial fibrillation when patients meet at least 2 of the following criteria: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL (133 μmol/L) 1

Clinical Context for Combined Use

• When a NOAC (like apixaban) is used in combination with clopidogrel, the lowest approved dose effective for stroke prevention tested in AF trials should be considered 1
• For patients with atrial fibrillation undergoing PCI or with acute coronary syndrome, dual therapy with clopidogrel 75 mg/day and oral anticoagulation should be considered as an alternative to triple antithrombotic therapy in patients where bleeding risk outweighs ischemic risk 1

Specific Dosing Algorithm

Step 1: Assess Apixaban Dose-Reduction Criteria

• If patient meets ≥2 criteria (age ≥80 years, weight ≤60 kg, creatinine ≥1.5 mg/dL): Use apixaban 2.5 mg twice daily 1
• If patient meets <2 criteria: Use apixaban 5 mg twice daily 1

Step 2: Determine Clopidogrel Dosing

• Maintenance dose is always 75 mg once daily regardless of patient characteristics 1, 2
• Loading doses (300-600 mg) are only used in acute settings (ACS, PCI) and are not part of chronic maintenance therapy 3, 2

Step 3: Minimize Triple Therapy Duration

• Triple therapy (aspirin + clopidogrel + apixaban) should be limited to 1 month maximum after PCI with stenting 1
• After 1 month, discontinue aspirin and continue dual therapy with clopidogrel 75 mg daily plus apixaban at the appropriate dose 1

Critical Safety Considerations

Bleeding Risk Management

• The combination of clopidogrel and apixaban significantly increases bleeding risk compared to monotherapy 1, 4
• Major bleeding rates with appropriately reduced-dose apixaban (2.5 mg twice daily) plus antiplatelet therapy were 13.7% in the AUGUSTUS trial 4
• Patients receiving dual therapy should have time in therapeutic range monitored if transitioning from warfarin, with target INR 2.0-2.5 when triple therapy is necessary 1

Duration of Combined Therapy

• Discontinuation of antiplatelet treatment in patients treated with oral anticoagulation should be considered at 12 months 1
• Beyond 12 months, oral anticoagulation alone is superior to combination therapy for most patients, as the bleeding risk outweighs additional thrombotic protection 1

Common Pitfalls to Avoid

• Do not use prasugrel or ticagrelor instead of clopidogrel when combining with oral anticoagulation, as these agents are not recommended as part of triple antithrombotic therapy 1
• Do not inappropriately dose-reduce apixaban in patients who do not meet criteria, as this was associated with similar bleeding rates but potentially reduced efficacy 4
• Do not continue triple therapy beyond 1 month unless very high ischemic risk features are present, as bleeding risk peaks within the first 30 days 1
• Do not use rivaroxaban 20 mg daily when combining with antiplatelet therapy; the reduced dose of 15 mg daily should be considered instead 1