What are the indications for combination therapy with Eliquis (apixaban) and aspirin (acetylsalicylic acid)?

Indications for Combination Therapy with Eliquis and Aspirin

Combination therapy with Eliquis (apixaban) and aspirin is only indicated in specific clinical scenarios, primarily in patients with mechanical heart valves, recent acute coronary syndrome, or recent percutaneous coronary intervention, and should be limited to the shortest necessary duration due to increased bleeding risk.

Primary Indications

1. Mechanical Heart Valves

• Patients with prosthetic heart valves who have had a TIA and are already on adequate oral anticoagulation should receive a combination of oral anticoagulants plus aspirin (81 mg/day) 1
• Note: While apixaban is mentioned here, warfarin remains the preferred anticoagulant for mechanical valves

2. Recent Acute Coronary Syndrome (ACS) with Atrial Fibrillation

• For patients with atrial fibrillation who develop ACS and require PCI:
  • Triple therapy (OAC + P2Y12 inhibitor + aspirin) should be limited to 30 days or less 1
  • After initial period, aspirin should be discontinued while continuing P2Y12 inhibitor (preferably clopidogrel) and anticoagulation 1
  • Apixaban is preferred over warfarin in this setting due to lower bleeding risk 1

3. Recent Percutaneous Coronary Intervention (PCI) with Atrial Fibrillation

• For patients with atrial fibrillation who undergo PCI:
  • If <6 months since PCI: Continue P2Y12 inhibitor (preferably clopidogrel) with apixaban and discontinue aspirin 1
  • If 6-12 months since PCI: Continue either aspirin or clopidogrel with apixaban until 1 year post-PCI 1
  • After 12 months: Discontinue antiplatelet therapy and continue apixaban alone 1

4. Unstable Angina or Non-Q-Wave Myocardial Infarction with TIA History

• Patients with recent TIA and unstable angina or non-Q-wave MI should be treated with a combination of clopidogrel 75mg and aspirin 75-100mg 1

Important Considerations and Risks

Bleeding Risk

• The FDA label for Eliquis specifically warns that concomitant use of antiplatelet agents increases bleeding risk 2
• In the APPRAISE-2 trial, the combination of apixaban with antiplatelet therapy in post-ACS patients showed:
  • 2.8% annual major bleeding rate with single antiplatelet therapy (vs 0.6% with placebo)
  • 5.9% annual major bleeding rate with dual antiplatelet therapy (vs 2.5% with placebo) 2
• In ARISTOTLE, concomitant aspirin use increased bleeding risk with apixaban from 1.8% to 3.4% per year 2, 3

Duration of Combination Therapy

• The AUGUSTUS trial showed that beyond 30 days, aspirin continues to increase bleeding without significantly reducing ischemic events when added to apixaban plus P2Y12 inhibitor 4
• For most indications, combination therapy should be limited to the shortest necessary duration

When Combination Therapy is NOT Indicated

1. Atrial Fibrillation for Stroke Prevention

   • Adding antiplatelet treatment to anticoagulation is not recommended in patients with AF to prevent recurrent embolic stroke 1
   • Antiplatelet drugs are not an alternative to OAC and should not be used for stroke prevention 1

2. Stable Coronary Artery Disease >12 months after PCI

   • For patients with stable coronary disease >12 months after PCI, antiplatelet medications should be discontinued and anticoagulation alone continued 1

3. Primary Prevention of Cardiovascular Disease

   • For patients on aspirin for primary prevention who develop a condition requiring anticoagulation, aspirin should be discontinued 1

Clinical Decision Algorithm

1. Assess if patient has a clear indication for combination therapy:

   • Mechanical heart valve
   • Recent ACS or PCI (<12 months)
   • Unstable angina with TIA history

2. If yes to any of the above:

   • Determine appropriate duration based on time since event
   • Use lowest effective dose of aspirin (≤100 mg)
   • Consider proton pump inhibitor to reduce GI bleeding risk 1
   • Monitor closely for bleeding complications

3. If no clear indication exists:

   • Use apixaban monotherapy without aspirin
   • Discontinue any existing antiplatelet therapy unless another specific indication exists

Common Pitfalls to Avoid

1. Prolonged triple therapy - Extending triple therapy (OAC + dual antiplatelet) beyond 30 days significantly increases bleeding without additional ischemic protection 1, 4

2. Unnecessary combination therapy - Many clinicians continue aspirin with anticoagulation without a clear indication, which increases bleeding risk without benefit 1

3. Overlooking drug interactions - When using combination therapy, be aware of potential drug interactions that may affect apixaban levels 1

4. High-dose aspirin - When combination therapy is indicated, aspirin dose should not exceed 100 mg 1