What is the recommended loading dose for acute myocardial infarction (MI)?

Loading Doses for Acute Myocardial Infarction

For acute MI, administer aspirin 162-325 mg orally as a loading dose immediately, followed by clopidogrel 300-600 mg (or prasugrel 60 mg/ticagrelor 180 mg if undergoing PCI), with aspirin chewed when possible for faster onset. 1

Aspirin Loading Dose

The cornerstone antiplatelet loading dose is aspirin 162-325 mg orally, administered as soon as possible on presentation. 1

• Non-enteric coated aspirin should be chewed to achieve faster onset of antiplatelet action 1
• This loading dose should be given even if the patient is already on daily aspirin therapy 1
• If oral administration is not possible, rectal or intravenous routes (where available) are acceptable alternatives 1
• The 162.5 mg dose has been shown to reduce vascular death by 23% at 5 weeks in acute MI 1

Alternative Routes When Oral Not Feasible

• Intravenous aspirin: 250-500 mg can be used 2
• Rectal aspirin: acceptable alternative route 1
• Caution: High-dose IV aspirin (>400 mg) may increase in-hospital mortality and should be avoided 3

P2Y12 Inhibitor Loading Doses

The choice of P2Y12 inhibitor depends on the MI type and management strategy:

For STEMI Managed with Primary PCI

Prasugrel 60 mg or ticagrelor 180 mg should be administered to reduce major adverse cardiovascular events and stent thrombosis 1

• Prasugrel 60 mg loading dose is preferred once coronary anatomy is known 1
  • Contraindicated in patients with prior stroke/TIA 1
  • Use caution if age ≥75 years or weight <60 kg 1
• Ticagrelor 180 mg loading dose is an equally effective alternative 1
  • Must be used with aspirin ≤100 mg daily for maintenance 1

For STEMI Managed with Fibrinolytic Therapy

Clopidogrel should be administered concurrently with fibrinolysis 1

• Age ≤75 years: 300 mg loading dose 1
• Age >75 years: No loading dose; start with 75 mg daily 1
• This reduces death and major adverse cardiovascular events 1

For NSTE-ACS or When PCI Timing Uncertain

Clopidogrel 300-600 mg loading dose (preferably 600 mg for more rapid platelet inhibition) 1, 2

• The 600 mg loading dose achieves more extensive and rapid platelet inhibition compared to 300 mg 1
• If PCI is anticipated >24 hours, upstream treatment with clopidogrel or ticagrelor may be considered 1

Post-PCI Loading Adjustments

If Patient Did Not Receive Loading Dose Before PCI

After fibrinolytic therapy:

• PCI ≤24 hours post-fibrinolysis: Clopidogrel 300 mg loading dose 1
• PCI >24 hours post-fibrinolysis: Clopidogrel 600 mg loading dose 1
• PCI >24 hours after fibrin-specific agent: Prasugrel 60 mg is reasonable, but not sooner than 24 hours after fibrinolytic 1

If patient already received clopidogrel loading with fibrinolytic:

• Continue clopidogrel 75 mg daily without additional loading dose 1

Critical Timing Considerations

Aspirin and P2Y12 inhibitors should be administered as early as possible, ideally before primary PCI when feasible 2

• The antiplatelet effect of aspirin begins within hours when given as a loading dose 4
• Initiating clopidogrel without a loading dose delays the antiplatelet effect by several days 4
• In acute thrombotic phases, rapid and complete platelet blockade is essential 5

Common Pitfalls to Avoid

• Do not use enteric-coated aspirin for loading - it delays absorption and onset of action 1
• Do not give prasugrel to patients with prior stroke/TIA - this is an absolute contraindication 1
• Do not skip the aspirin loading dose in patients already on daily aspirin - additional loading further inhibits platelet function in acute MI 1, 6
• Do not use high-dose IV aspirin (>400 mg) - associated with increased in-hospital mortality 3
• Do not give prasugrel within 24 hours of fibrinolytic therapy - wait at least 24 hours after fibrin-specific agents 1

Maintenance Therapy After Loading

Following the loading doses, transition to maintenance therapy:

• Aspirin 75-100 mg daily (81 mg preferred in US) indefinitely 1
• P2Y12 inhibitor for at least 12 months: clopidogrel 75 mg daily, prasugrel 10 mg daily (5 mg if weight <60 kg or age ≥75 years), or ticagrelor 90 mg twice daily 1