Is early discontinuation of aspirin (acetylsalicylic acid) recommended in patients with low-risk acute myocardial infarction (AMI)?

Early Discontinuation of Aspirin in Low-Risk AMI

In low-risk AMI patients who do NOT require oral anticoagulation, early aspirin discontinuation is NOT recommended—aspirin should be continued indefinitely for secondary prevention. However, in low-risk AMI patients who DO require oral anticoagulation (e.g., atrial fibrillation), aspirin should be discontinued after 1-4 weeks of triple therapy, continuing only P2Y12 inhibitor (preferably clopidogrel) plus anticoagulant to reduce bleeding risk. 1

Standard Approach: Low-Risk AMI WITHOUT Anticoagulation Indication

Aspirin should be continued indefinitely in patients after AMI who do not require anticoagulation, as this represents the cornerstone of secondary prevention. 1

• Initial loading dose: 162-325 mg non-enteric coated aspirin should be administered as soon as possible on presentation 1
• Maintenance therapy: 75-100 mg daily aspirin should be continued indefinitely after AMI 1, 2
• Mortality benefit: Low-dose aspirin reduces vascular death, MI, and stroke by approximately 22% for every 39 mg/dL reduction in cardiovascular events, preventing 15 serious vascular events per 1000 patients treated annually 3, 4
• Bleeding risk is acceptable: The absolute increase in major bleeding is 20-50 fold smaller than the cardiovascular benefit in secondary prevention settings 3

Recent Evidence on P2Y12 Monotherapy Strategy

The 2025 TARGET-FIRST trial evaluated a different question—whether P2Y12 inhibitor monotherapy (discontinuing aspirin but continuing P2Y12 inhibitor) after 1 month could be safe in highly selected low-risk AMI patients. 5

• Study population: Low-risk AMI patients with successful complete revascularization, contemporary drug-eluting stents, and no complications after 1 month of dual antiplatelet therapy 5
• Results: P2Y12 monotherapy was noninferior for cardiovascular events (2.1% vs 2.2%) and superior for bleeding reduction (2.6% vs 5.6% for clinically relevant bleeding) 5
• Critical limitation: This strategy is NOT yet incorporated into 2025 ACC/AHA guidelines and should be considered investigational for patients without anticoagulation indications 1

Special Circumstance: Low-Risk AMI WITH Anticoagulation Indication

This is the ONLY scenario where early aspirin discontinuation is guideline-recommended. 1

Specific Recommendations

• Discontinue aspirin after 1-4 weeks of triple antithrombotic therapy (aspirin + P2Y12 inhibitor + oral anticoagulant) 1
• Continue P2Y12 inhibitor (preferably clopidogrel) plus oral anticoagulant for at least 12 months after PCI 1
• Prefer DOACs over warfarin due to favorable efficacy and safety profile 1
• Use clopidogrel as the P2Y12 inhibitor rather than prasugrel or ticagrelor, as trials of more potent agents excluded patients requiring anticoagulation 1

Evidence Supporting Early Aspirin Discontinuation in Anticoagulated Patients

• Multiple RCTs demonstrate safety: Several trials (including AUGUSTUS) show aspirin discontinuation 1-4 weeks after PCI reduces bleeding risk in patients with atrial fibrillation requiring dual antiplatelet therapy and oral anticoagulation 1
• No difference in mortality or stroke: Meta-analyses show no difference in mortality, stroke, or overall MACE when aspirin is discontinued in patients on oral anticoagulation 1
• Marginal increase in MI/stent thrombosis: There is a small numerical increase in MI and stent thrombosis, though individual studies were not powered for these endpoints 1
• ESC 2024 guidelines concur: Early cessation (≤1 week) of aspirin is recommended in AF patients with ACS undergoing uncomplicated PCI if thrombosis risk is low or bleeding risk is high 1

Stent Thrombosis Risk Considerations

In patients with high risk of stent thrombosis, aspirin for up to 30 days after PCI could be considered before discontinuation. 1

• 80% of stent thrombosis events occur within 30 days of PCI 1
• High-risk features include: Complex stents, bifurcation lesions, history of stent thrombosis, or incomplete revascularization 2
• AUGUSTUS trial data: Stent thrombosis events were numerically less frequent in those receiving aspirin (randomization approximately 1 week after PCI) compared with placebo 1

Common Pitfalls to Avoid

• Do not discontinue aspirin in standard AMI patients without anticoagulation indication—the mortality benefit substantially outweighs bleeding risk in secondary prevention 1, 3, 4
• Do not use ticagrelor or prasugrel with triple therapy—clopidogrel is preferred when combining with anticoagulation 1
• Do not discontinue both antiplatelet agents simultaneously in patients with recent stents—this dramatically increases stent thrombosis risk 2, 6
• Do not extend triple therapy beyond 4 weeks in most patients—bleeding risk increases without additional ischemic benefit 1
• Do not use aspirin doses >100 mg for maintenance—higher doses increase bleeding without improving cardiovascular outcomes 1, 6

Algorithm for Decision-Making

1. Does the patient require long-term oral anticoagulation? (atrial fibrillation, venous thromboembolism, prosthetic valve)

   • YES: Discontinue aspirin after 1-4 weeks; continue clopidogrel + DOAC for 12 months 1
   • NO: Continue aspirin 75-100 mg daily indefinitely 1, 2

2. If discontinuing aspirin due to anticoagulation, assess stent thrombosis risk:

   • High risk features present: Consider continuing aspirin up to 30 days post-PCI 1
   • Low risk/uncomplicated PCI: Discontinue aspirin at 1 week 1

3. If bleeding occurs on dual therapy (aspirin + P2Y12 inhibitor):

   • Life-threatening bleeding: Discontinue both agents temporarily; consult cardiology urgently 6
   • Significant but not life-threatening: Add PPI; consider reducing to single antiplatelet agent based on time from event 2, 6