Should aspirin (acetylsalicylic acid) be continued in patients with atrial fibrillation or cardiovascular disease who are taking Eliquis (apixaban)?

Should You Continue Aspirin on Eliquis?

No, aspirin should be discontinued in most patients taking Eliquis (apixaban) for atrial fibrillation, as the combination significantly increases bleeding risk without providing meaningful additional protection against ischemic events. 1

General Principle for Atrial Fibrillation

For patients with atrial fibrillation on Eliquis, anticoagulation alone is the standard therapy—aspirin adds only bleeding risk without stroke prevention benefit. 2

• The combination of aspirin and anticoagulation doubles the bleeding risk compared to anticoagulation alone (rate ratio 2.14) without reducing ischemic events 3
• Apixaban monotherapy is superior to the combination of aspirin plus anticoagulation for stroke prevention in AF 4, 2

Decision Algorithm Based on Clinical Scenario

Scenario 1: Atrial Fibrillation WITHOUT Recent Coronary Events

Stop aspirin immediately and continue Eliquis alone. 1

• This applies to patients with stable coronary disease, prior stroke/TIA, peripheral artery disease, or primary prevention 1
• Even in patients with documented coronary artery disease, apixaban alone provides equivalent protection against myocardial infarction compared to the combination with aspirin 5

Scenario 2: Recent PCI (Percutaneous Coronary Intervention)

The timing since PCI determines the regimen:

• <6 months post-PCI: Stop aspirin, continue clopidogrel (not aspirin) with Eliquis 1
• 6-12 months post-PCI: Continue either aspirin OR clopidogrel (single antiplatelet) with Eliquis until 12 months post-PCI 1
• >12 months post-PCI: Stop all antiplatelet therapy, continue Eliquis alone 1, 4

Critical caveat: If triple therapy (Eliquis + aspirin + clopidogrel) is used immediately post-PCI in very high-risk patients, limit duration to maximum 1 month, then drop aspirin 1, 2

Scenario 3: Recent Acute Coronary Syndrome (ACS)

• <12 months since ACS: Stop aspirin, continue clopidogrel with Eliquis 1
• >12 months since ACS: Stop all antiplatelet therapy, continue Eliquis alone 1

Scenario 4: Post-CABG Surgery

• <12 months post-CABG: May continue aspirin (<100 mg/day) with Eliquis 1
• >12 months post-CABG: Stop aspirin, continue Eliquis alone 1, 4

Evidence Supporting Aspirin Discontinuation

The AUGUSTUS trial provides the strongest evidence against routine aspirin use with apixaban:

• Aspirin increased total bleeding events by 114% (rate ratio 2.14) compared to placebo when added to apixaban plus clopidogrel 3
• No significant reduction in ischemic events with aspirin (rate ratio 0.75, not statistically significant) 3
• Apixaban plus clopidogrel without aspirin is now the standard therapy for AF patients with recent ACS or PCI 3, 6

This benefit of dropping aspirin applies regardless of baseline bleeding or stroke risk:

• Aspirin increased bleeding in both low (HAS-BLED ≤2) and high (HAS-BLED ≥3) bleeding risk patients 6
• The hazard of aspirin was consistent across all CHA2DS2-VASc scores 6

Medication Selection Preferences

When antiplatelet therapy IS indicated (early post-PCI/ACS period):

• Prefer clopidogrel over prasugrel or ticagrelor when combined with anticoagulation due to lower bleeding risk 1, 2
• Patients on multiple bleeding events were more likely to be on high-potency P2Y12 inhibitors 3

Common Pitfalls to Avoid

The most common error is continuing triple therapy (Eliquis + aspirin + clopidogrel) beyond the immediate post-PCI period—this causes preventable major bleeding. 2

• Do not add aspirin to Eliquis for "extra protection" in patients with vascular disease—anticoagulation is superior for stroke prevention, and aspirin only adds bleeding risk 2, 7
• Do not continue aspirin indefinitely after coronary interventions in AF patients on anticoagulation—the bleeding risk outweighs any theoretical ischemic benefit after the initial high-risk period 1
• Aspirin use should be limited to very specific time windows post-revascularization, not continued indefinitely 1

Bleeding Risk Mitigation

When anticoagulation is necessary:

• Use proton pump inhibitors for gastrointestinal protection 2
• Optimize blood pressure control 2
• Avoid NSAIDs and other medications that increase bleeding risk 2
• Monitor renal function and adjust Eliquis dosing accordingly (reduce to 2.5 mg twice daily if patient has any two of: age ≥80 years, weight ≤60 kg, creatinine ≥1.5 mg/dL) 4