Do patients on Eliquis (apixaban) still need aspirin or Plavix (clopidogrel)?

Patients on Eliquis (Apixaban) Generally Do Not Need Additional Aspirin or Plavix

For most patients taking Eliquis (apixaban) for stroke prevention in atrial fibrillation, adding aspirin or Plavix (clopidogrel) is not recommended due to significantly increased bleeding risk without additional benefit in preventing thromboembolism.

Rationale for Avoiding Combination Therapy

Evidence from Guidelines and Drug Information

• The FDA drug label for apixaban (Eliquis) specifically warns that coadministration with antiplatelet agents increases bleeding risk 1
• In the ARISTOTLE trial, concomitant use of aspirin increased bleeding risk on apixaban from 1.8% per year to 3.4% per year 1
• The APPRAISE-2 trial (evaluating apixaban with antiplatelet therapy in post-acute coronary syndrome patients) was terminated early due to higher bleeding rates with apixaban plus antiplatelet therapy compared to placebo 1

Specific Clinical Scenarios

For Atrial Fibrillation Patients

• For patients with nonvalvular atrial fibrillation, anticoagulation with apixaban alone is recommended based on CHA₂DS₂-VASc score 2
• The 2014 AHA/ACC/HRS guidelines recommend individualized antithrombotic therapy based on shared decision-making after discussion of absolute and relative risks 2

For Patients with Recent Coronary Intervention

• For patients with AF who undergo PCI (percutaneous coronary intervention):
  • During the required DAPT (dual antiplatelet therapy) period after stenting, a carefully managed triple therapy period may be necessary
  • After this period, clopidogrel may be considered concurrently with oral anticoagulants but without aspirin in patients with CHA₂DS₂-VASc score ≥2 2
  • Bare-metal stents may be considered to minimize duration of DAPT 2

For Patients with Venous Thromboembolism

• For patients being treated with apixaban for venous thromboembolism (VTE):
  • If the patient has no history of acute coronary syndrome (ACS) or recent stent placement, antiplatelet therapy should be stopped and apixaban used alone 2
  • If it has been >12 months since ACS, antiplatelet therapy may be stopped and most patients can be treated with anticoagulation alone 2

Exceptions Where Combination Therapy May Be Considered

1. Recent Coronary Stenting:

   • If <6 months since PCI: Stop aspirin, continue clopidogrel, and use apixaban 2
   • If 6-12 months since PCI: Continue single antiplatelet therapy with either aspirin or clopidogrel until 1 year post-PCI, along with apixaban 2

2. Recent CABG Surgery:

   • If <1 year post-CABG: Continue aspirin (<100 mg/day) with apixaban 2
   • If >1 year post-CABG: Stop aspirin and use apixaban alone 2

3. Recent Acute Coronary Syndrome:

   • If <12 months since ACS: Stop aspirin, continue P2Y12 inhibitor (preferably clopidogrel), and use apixaban 2
   • For selected high thrombotic risk patients with low bleeding risk: Consider continuing single antiplatelet therapy beyond 12 months 2

Common Pitfalls to Avoid

1. Unnecessary Triple Therapy: Combining apixaban with both aspirin and clopidogrel substantially increases bleeding risk and should be avoided unless absolutely necessary for a limited time period

2. Overlooking Drug Interactions: Apixaban is a substrate of both CYP3A4 and P-gp; certain medications may increase bleeding risk when combined with apixaban 1

3. Failing to Reassess: The need for anticoagulation should be reevaluated at periodic intervals 2

4. Inappropriate Dosing: For patients requiring both apixaban and antiplatelet therapy, ensure appropriate apixaban dosing based on age, weight, and renal function to minimize bleeding risk

5. Ignoring Renal Function: Evaluate renal function before initiation of apixaban and reevaluate when clinically indicated and at least annually 2

Remember that the decision to use combination therapy must carefully weigh thrombotic risk against bleeding risk, with the understanding that for most patients on apixaban, additional antiplatelet therapy provides more harm than benefit.