Is it appropriate to continue aspirin long-term in a patient who had a recent coronary stent and is already on apixaban (Eliquis) and clopidogrel 75 mg?

Triple Antithrombotic Therapy After Coronary Stenting

This regimen is NOT appropriate for routine use—triple therapy (aspirin + clopidogrel + apixaban) significantly increases major bleeding risk without proven mortality or morbidity benefit, and current evidence supports transitioning to dual therapy (apixaban + clopidogrel alone) as soon as safely possible after the immediate post-stent period. 1

Immediate Post-Stent Period (First 1-4 Weeks)

For patients requiring both anticoagulation (for atrial fibrillation or other indication) and dual antiplatelet therapy after stent placement, a brief period of triple therapy may be necessary but should be minimized:

• Aspirin should be discontinued at hospital discharge in most patients to reduce bleeding risk while maintaining adequate thrombotic protection 1
• If thrombotic risk is particularly high (complex PCI, multiple stents, left main disease), aspirin may be continued for up to 1 month maximum 1
• During any triple therapy period, use the lowest effective aspirin dose (75-81 mg daily) rather than higher doses (162-325 mg), as lower doses provide equivalent efficacy with less bleeding 2, 3

Transition to Dual Therapy (Standard Approach)

The evidence-based regimen is apixaban + clopidogrel 75 mg (without aspirin) for 12 months post-stent: 1

• This dual therapy approach reduces major bleeding by approximately 50% compared to triple therapy while maintaining similar rates of cardiovascular death, myocardial infarction, and stroke 1
• Research specifically examining apixaban in this context (APPRAISE-2 trial) demonstrated increased bleeding with triple therapy regardless of whether aspirin alone or aspirin + clopidogrel was used 4

Duration of Clopidogrel

Continue clopidogrel for the full recommended duration based on stent type:

• Bare-metal stent: Minimum 1 month, ideally up to 12 months 2
• Drug-eluting stent: At least 12 months if not at high bleeding risk 2, 5
• After completing the clopidogrel course, continue apixaban monotherapy indefinitely for the underlying indication (e.g., atrial fibrillation) 1

Critical Bleeding Risk Considerations

The combination of apixaban with dual antiplatelet therapy increases Thrombolysis In Myocardial Infarction (TIMI) major bleeding 2.4-6.6 fold compared to placebo: 4

• Patients on triple therapy require close monitoring for bleeding complications
• Any patient with active bleeding, recent major bleeding, or high bleeding risk scores should have aspirin discontinued immediately
• The bleeding risk with triple therapy outweighs any theoretical ischemic benefit in most clinical scenarios 6

Common Pitfalls to Avoid

• Do not continue triple therapy beyond the immediate periprocedural period (maximum 1 month) unless there are extraordinary thrombotic circumstances requiring cardiology consultation 1
• Do not use high-dose aspirin (162-325 mg) if triple therapy is deemed necessary; stick to 75-81 mg 2
• Do not assume all three agents are required for the full 12 months—this outdated approach substantially increases bleeding without improving outcomes 1, 4
• Do not discontinue clopidogrel prematurely (before minimum duration) as this increases stent thrombosis risk dramatically 2, 5

Practical Algorithm

1. At discharge: Apixaban + clopidogrel 75 mg + aspirin 75-81 mg (if high thrombotic risk only)
2. At 1 month maximum: Stop aspirin, continue apixaban + clopidogrel 75 mg
3. At 12 months: Stop clopidogrel, continue apixaban monotherapy indefinitely
4. If bleeding occurs at any point: Immediately discontinue aspirin (if still taking), consider stopping clopidogrel if life-threatening bleeding and consult cardiology