Does taking Plavix (clopidogrel) impact the use of Eliquis (apixaban)?

Combining Eliquis (Apixaban) with Plavix (Clopidogrel)

The combination of Eliquis (apixaban) and Plavix (clopidogrel) significantly increases bleeding risk and should be used only for specific indications with careful monitoring and for the shortest duration necessary.

Bleeding Risk Assessment

When combining Eliquis and Plavix, the following considerations are critical:

• The combination of apixaban with antiplatelet agents, including clopidogrel, increases bleeding risk 1
• Dual therapy with an oral anticoagulant and a single antiplatelet agent (typically clopidogrel) carries a lower bleeding risk than triple therapy but still higher than monotherapy 2
• A recent study found no significant difference in major bleeding risk between rivaroxaban+clopidogrel and apixaban+clopidogrel combinations (incidence rates of 7.96 vs 7.38 per 100 person-years) 3

Clinical Indications for Combination Therapy

The combination is primarily indicated in patients with:

1. Atrial fibrillation with recent coronary stenting:

   • After a short period (up to 1 week) of triple therapy, dual therapy with a NOAC (like apixaban) and a single antiplatelet agent (preferably clopidogrel) is recommended 2
   • Discontinuation of antiplatelet treatment in patients treated with an oral anticoagulant is recommended after 12 months 2

2. Recent acute coronary syndrome with atrial fibrillation:

   • For patients with atrial fibrillation and CHA₂DS₂-VASc score ≥1 in men and ≥2 in women who have had an acute coronary event, dual therapy with a NOAC and clopidogrel is the default strategy after a short period of triple therapy 2

Duration of Combination Therapy

• Limit the duration of combined therapy to the shortest necessary period:
  • For most patients with AF and coronary stenting, dual therapy should be limited to 12 months 2
  • In patients at high bleeding risk, even shorter durations may be considered

Dosing Considerations

When using apixaban with clopidogrel:

• Standard apixaban dosing is 5mg twice daily, but should be reduced to 2.5mg twice daily for patients with at least two of: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL 1
• The standard dose of clopidogrel is 75mg daily, with a 300mg loading dose in patients younger than 75 years 2

Monitoring Recommendations

Patients on combination therapy require:

• Regular assessment for bleeding signs (unexplained bruising, blood in urine or stool, unusual headaches)
• Periodic evaluation of renal and hepatic function
• Consideration of proton pump inhibitors to reduce gastrointestinal bleeding risk 2
• Fall risk assessment, as falls can increase bleeding complications, particularly intracranial hemorrhage 1

Special Considerations

• Renal function: Apixaban is 27% renally excreted and should be used with caution in patients with CrCl 15-30 mL/min and avoided in severe renal impairment (CrCl <15 mL/min) 1, 2
• Drug interactions: Strong inhibitors of both CYP3A4 and P-glycoprotein (e.g., ketoconazole, ritonavir) are contraindicated with apixaban 1
• Elderly patients: Higher bleeding risk requires careful monitoring and possibly dose adjustment

Practical Management Algorithm

1. Determine if combination therapy is absolutely necessary

   • Is the patient post-ACS or post-PCI with concurrent atrial fibrillation?
   • Is there another compelling indication for dual therapy?

2. If combination needed:

   • Use for shortest duration necessary (typically ≤12 months)
   • Consider proton pump inhibitor for GI protection
   • Monitor for bleeding signs regularly
   • Adjust apixaban dose based on age, weight, and renal function

3. If bleeding occurs:

   • For minor bleeding: Consider continuing therapy with closer monitoring
   • For major bleeding: Consider discontinuing one agent (typically the antiplatelet)
   • For life-threatening bleeding: Consider specific reversal agents like idarucizumab for dabigatran or prothrombin complex concentrates for apixaban 2

Remember that the mortality and morbidity benefits of preventing thrombotic events must be carefully balanced against the increased risk of bleeding when combining these medications.