Can I take Eliquis (apixaban) with Aspirin (ASA)?

Taking Eliquis (Apixaban) with Aspirin (ASA)

Taking Eliquis (apixaban) with aspirin significantly increases bleeding risk and should generally be avoided unless there is a specific clinical indication that outweighs this risk.

Bleeding Risk Assessment

The combination of apixaban and aspirin substantially increases bleeding risk compared to either agent alone:

• The FDA label for Eliquis (apixaban) explicitly warns that "coadministration of antiplatelet agents, fibrinolytics, heparin, aspirin, and chronic NSAID use increases the risk of bleeding" 1
• Clinical trial evidence shows that adding aspirin to apixaban increases bleeding risk from 1.8% per year to 3.4% per year 1
• Even low-dose aspirin (100 mg) carries a significant bleeding risk with an odds ratio of 1.6, which increases to 2.6 with higher doses (300 mg) 2

Specific Clinical Scenarios

1. Atrial Fibrillation

• For most patients with atrial fibrillation requiring anticoagulation, apixaban alone is preferred over combination therapy with aspirin
• The ARISTOTLE trial showed that apixaban had beneficial effects on stroke prevention and caused less major bleeding than warfarin, regardless of whether patients were taking aspirin 3

2. Recent Acute Coronary Syndrome (ACS) or Percutaneous Coronary Intervention (PCI)

• For patients with atrial fibrillation who have undergone PCI or had ACS:
  • The AUGUSTUS trial demonstrated that apixaban plus a P2Y12 inhibitor without aspirin was associated with less bleeding than regimens including aspirin 4
  • Short-term triple therapy (apixaban, P2Y12 inhibitor, and aspirin) may be necessary immediately after PCI, but aspirin should be discontinued early to reduce bleeding risk 2

3. History of Stroke or TIA

• For patients with subclinical atrial fibrillation and history of stroke/TIA:
  • The ARTESiA trial showed apixaban reduced stroke risk compared to aspirin (absolute risk reduction of 7% over 3.5 years), but with a 3% increase in major bleeding 5
  • The benefit-risk ratio favors apixaban over aspirin in this high-risk population

Algorithm for Decision-Making

1. Determine if there is a compelling indication for dual therapy:

   • Recent coronary stent placement (particularly drug-eluting stent)
   • Acute coronary syndrome within past 12 months
   • High-risk vascular disease with low bleeding risk

2. If dual therapy is necessary:

   • Use the lowest effective dose of aspirin (≤100 mg daily) 2
   • Limit the duration of combination therapy to the shortest necessary period
   • Consider proton pump inhibitor therapy to reduce gastrointestinal bleeding risk

3. For most patients with atrial fibrillation:

   • Use apixaban monotherapy without aspirin unless there is a specific indication for dual therapy
   • When aspirin is discontinued, do not increase the apixaban dose

Important Cautions

• The APPRAISE-2 trial was terminated early due to excessive bleeding with apixaban plus aspirin in high-risk post-ACS patients 1
• When apixaban and aspirin are used together, the bleeding risk is substantially higher than with either agent alone
• If dual therapy is necessary, close monitoring for bleeding complications is essential

Remember that for most patients requiring anticoagulation with apixaban, adding aspirin increases bleeding risk without providing additional thrombotic protection, unless there is a specific indication for dual therapy.