Is it safe to use Eliquis (apixaban) and Plavix (clopidogrel) together?

Dual Use of Eliquis (Apixaban) and Plavix (Clopidogrel)

The combination of Eliquis (apixaban) and Plavix (clopidogrel) significantly increases bleeding risk and should generally be limited to specific clinical scenarios with time-limited duration, such as in patients with both atrial fibrillation and recent coronary stenting. 1

Indications for Dual Therapy

• Dual antithrombotic therapy with apixaban and clopidogrel is primarily indicated in patients who have both:

  • An indication for oral anticoagulation (such as atrial fibrillation)
  • AND a recent coronary intervention or acute coronary syndrome 1

• This combination is typically used as part of a planned transition from triple therapy (oral anticoagulant + dual antiplatelet therapy) to reduce bleeding risk while maintaining antithrombotic protection 1

• When used, apixaban should be administered at the lowest approved dose effective for stroke prevention in atrial fibrillation patients 1

Bleeding Risk Considerations

• The combination of apixaban and clopidogrel carries a significantly higher bleeding risk compared to either agent alone 2, 3

• In patients with acute coronary syndrome, adding apixaban to dual antiplatelet therapy (aspirin plus clopidogrel) resulted in unacceptably high rates of major bleeding 2, 3

• For patients requiring both anticoagulation and antiplatelet therapy, proton pump inhibitors should be considered to reduce gastrointestinal bleeding risk, though caution is advised with omeprazole and esomeprazole due to potential interaction with clopidogrel 1

Duration of Therapy

• When dual therapy with apixaban and clopidogrel is used, it should be time-limited based on clinical indication 1

• In patients with atrial fibrillation who undergo coronary stenting:

  • Dual therapy with clopidogrel and an oral anticoagulant may be considered as an alternative to initial triple therapy in selected patients 1
  • The duration should be limited to the minimum necessary time, typically up to 12 months 1

Management of Bleeding Complications

• If severe bleeding occurs during dual therapy with apixaban and clopidogrel:

  • Immediately interrupt both medications 1
  • For apixaban, consider 4-factor prothrombin complex concentrate 1
  • For clopidogrel, platelet transfusion may be considered, though effectiveness depends on timing of the most recent dose 1

• For non-severe bleeding:

  • Do not administer additional doses of either medication while bleeding is active 1
  • Local measures should be attempted before considering reversal agents 1

Special Considerations

• For patients requiring elective surgery while on this combination:

  • Clopidogrel should be stopped ≥5 days before surgery 1
  • Apixaban should be stopped 1-2 days before low bleeding risk procedures and 3 days before high bleeding risk procedures 1
  • Bridging with parenteral anticoagulation is generally not recommended 1

• For patients with mechanical heart valves, this combination is not well-studied and traditional vitamin K antagonists are preferred for the anticoagulant component 1

Conclusion

The combination of apixaban and clopidogrel significantly increases bleeding risk and should only be used in specific clinical scenarios with careful monitoring. When required, the duration should be minimized to the shortest necessary period to reduce bleeding complications while providing adequate antithrombotic protection.