When should aspirin and clopidogrel be given to patients with chronic myocardial infarcts (MI) as part of dual antiplatelet therapy (DAPT)?

Dual Antiplatelet Therapy in Chronic Myocardial Infarcts

Direct Answer

For patients with chronic (remote) myocardial infarction, aspirin 75-100 mg daily should be continued indefinitely as monotherapy for long-term secondary prevention, with clopidogrel 75 mg daily as an equally effective alternative if aspirin is not tolerated. 1, 2 Dual antiplatelet therapy (DAPT) with both aspirin and clopidogrel is NOT routinely recommended for chronic infarcts beyond the initial 6-12 month period post-MI unless specific high-risk features are present. 1, 2

Standard Post-MI Antiplatelet Strategy

Immediate Post-MI Period (First 6-12 Months)

• DAPT with aspirin 75-100 mg daily plus clopidogrel 75 mg daily is recommended for up to 6 months after MI 1, 2
• If PCI was performed, DAPT duration extends to 6-12 months depending on stent type and bleeding risk 1, 3
• For acute MI, clopidogrel should be initiated with a 300 mg loading dose followed by 75 mg daily maintenance 4

Chronic Phase (Beyond 6-12 Months)

• Transition to single antiplatelet therapy (aspirin OR clopidogrel monotherapy) is the standard approach 1, 2
• Aspirin 75-100 mg daily should be continued lifelong 2, 4
• Clopidogrel 75 mg daily is a safe and effective alternative to aspirin monotherapy 2, 5
• The CAPRIE trial demonstrated clopidogrel 75 mg daily reduced the composite of MI, stroke, or vascular death by 8.7% compared to aspirin in patients with prior MI 1, 4

When to Consider Extended DAPT in Chronic MI Patients

Extended DAPT beyond 12 months should only be considered in high ischemic risk patients without high bleeding risk. 1 The following criteria define high ischemic risk:

High Ischemic Risk Criteria

• Age >65 years 1
• Diabetes mellitus 1
• Second prior MI 1
• Multivessel coronary artery disease 1
• Chronic kidney disease 1
• Peripheral artery disease 1

Extended DAPT Options for High-Risk Patients

If high ischemic risk features are present AND bleeding risk is acceptable:

Option 1: Aspirin plus ticagrelor 60 mg twice daily 1

• Based on PEGASUS-TIMI 54 trial showing reduced ischemic events in patients 1-3 years post-MI with high-risk features 1
• NNT = 84 to prevent one ischemic event 1
• NNH = 81 for one major bleeding event 1
• Particularly beneficial in patients with diabetes, multivessel CAD, or PAD 1

Option 2: Aspirin plus rivaroxaban 2.5 mg twice daily 1

• Based on COMPASS trial in stable atherosclerotic disease 1
• NNT = 77 to prevent one ischemic event 1
• NNH = 84 for one major bleeding event 1
• Reduced all-cause mortality compared to aspirin alone 1
• Particularly beneficial in patients with diabetes, PAD, mild CKD, or active smoking 1

Option 3: Aspirin plus clopidogrel 75 mg daily 1

• Based on DAPT trial, though evidence quality is lower than for ticagrelor or rivaroxaban 1
• NNT = 63 to prevent one ischemic event 1
• NNH = 105 for one major bleeding event 1

Critical Timing Considerations

The decision to extend DAPT should be made at the 12-month mark after MI, not earlier. 1 This timing is based on:

• PEGASUS-TIMI 54 enrolled patients 1-3 years post-MI who had tolerated 12 months of DAPT 1
• Patients must demonstrate tolerance to initial DAPT without bleeding complications 1
• Ischemic and bleeding risk should be reassessed at regular intervals during extended therapy 1

Common Pitfalls and Caveats

Avoid These Errors:

1. Do NOT continue routine DAPT indefinitely in all chronic MI patients - this increases bleeding risk without proven benefit in unselected populations 1, 6
2. Do NOT use ticagrelor 90 mg twice daily for extended therapy - only the 60 mg twice daily dose is approved for long-term use due to better tolerability 1
3. Do NOT combine omeprazole or esomeprazole with clopidogrel - these PPIs significantly reduce clopidogrel's antiplatelet activity via CYP2C19 inhibition 2, 4
4. Do NOT prescribe extended DAPT without assessing bleeding risk - patients with high bleeding risk should receive monotherapy only 1, 2

Bleeding Risk Mitigation:

• Add a proton pump inhibitor (preferably NOT omeprazole/esomeprazole) for GI protection during any DAPT regimen 2, 7
• Consider pantoprazole, lansoprazole, or dexlansoprazole as safer PPI alternatives with clopidogrel 4
• Reassess bleeding and ischemic risk at regular intervals during extended therapy 1

Special Populations:

• CYP2C19 poor metabolizers: Consider alternative P2Y12 inhibitor (ticagrelor or prasugrel) instead of clopidogrel, as these patients have reduced clopidogrel efficacy 4
• Patients requiring oral anticoagulation: Triple therapy (aspirin + clopidogrel + anticoagulant) should be limited to ≤1 week, then transition to dual therapy with clopidogrel plus anticoagulant for up to 6 months, followed by anticoagulant alone 2, 8

Algorithm for Decision-Making

1. At 6-12 months post-MI: Assess for high ischemic risk features (age >65, diabetes, second MI, multivessel CAD, CKD, PAD) 1

2. If NO high ischemic risk features: Transition to aspirin 75-100 mg daily monotherapy (or clopidogrel 75 mg daily if aspirin intolerant) 1, 2

3. If high ischemic risk features present: Assess bleeding risk using validated tools 1

   • High bleeding risk: Continue monotherapy only 1, 2
   • Acceptable bleeding risk: Consider extended DAPT with aspirin plus ticagrelor 60 mg BID OR aspirin plus rivaroxaban 2.5 mg BID 1

4. During extended DAPT: Reassess bleeding and ischemic risk every 6-12 months 1