What is the recommended antiplatelet loading dose in acute myocardial infarction (AMI)?

Antiplatelet Loading Doses in Acute Myocardial Infarction

The recommended antiplatelet loading dose in acute myocardial infarction (AMI) is aspirin 150-325 mg (oral or IV if oral ingestion not possible) plus a P2Y12 inhibitor: clopidogrel 600 mg, prasugrel 60 mg, or ticagrelor 180 mg, with the specific P2Y12 inhibitor choice depending on the management strategy and patient characteristics. 1

Aspirin Loading Dose

• Administer aspirin as soon as possible after AMI diagnosis is deemed probable at a dose of 150-325 mg in a chewable form (avoid enteric-coated aspirin due to slow onset of action) 1
• If oral ingestion is not possible, intravenous administration of aspirin at a dose of 250-500 mg is an alternative 1
• After the loading dose, continue with a lower maintenance dose (75-160 mg) orally daily for life 1

P2Y12 Inhibitor Loading Doses

Clopidogrel

• For patients undergoing primary PCI: 600 mg oral loading dose (preferred over 300 mg due to more rapid and stronger inhibition of platelet aggregation) 1
• For patients receiving fibrinolytic therapy:
  • 300 mg loading dose if PCI is performed within 24 hours of fibrinolytic therapy 1
  • 600 mg loading dose if PCI is performed more than 24 hours after fibrinolytic therapy 1

Prasugrel

• Single 60 mg oral loading dose for patients undergoing primary PCI 2
• For patients who received fibrinolytic therapy: prasugrel 60 mg can be given if PCI is performed more than 24 hours after treatment with a fibrin-specific agent or more than 48 hours after a non-fibrin-specific agent 1
• Timing: In STEMI patients presenting within 12 hours of symptom onset, administer at the time of diagnosis, although most patients receive it at the time of PCI 2

Ticagrelor

• 180 mg loading dose followed by 90 mg twice daily maintenance dose 1
• The recommended maintenance dose of aspirin to be used with ticagrelor is 81 mg daily 1

Selection of P2Y12 Inhibitor

• Prasugrel and ticagrelor are more potent than clopidogrel, with faster onset of action (within 30 minutes compared to 2 hours for clopidogrel) 3
• Contraindications for prasugrel include:
  • History of prior stroke or transient ischemic attack 2
  • Generally not recommended in patients ≥75 years of age due to increased risk of fatal and intracranial bleeding 2
  • Use with caution in patients <60 kg (consider lower maintenance dose of 5 mg) 2

Important Clinical Considerations

• The loading dose of antiplatelet agents should be administered as soon as possible after AMI diagnosis, as many cardiovascular events occur within hours of initial presentation 2
• For patients with STEMI undergoing primary PCI, both aspirin and a P2Y12 inhibitor should be administered before or at the time of PCI 1
• For patients requiring urgent CABG after antiplatelet loading:
  • Aspirin should not be withheld before urgent CABG 1
  • Clopidogrel or ticagrelor should be discontinued at least 24 hours before urgent on-pump CABG, if possible 1
  • Prasugrel should be discontinued at least 7 days prior to any surgery when possible 2

Bleeding Risk Management

• Consider patient-specific bleeding risk factors when selecting antiplatelet therapy:
  • Body weight <60 kg
  • Age ≥75 years
  • History of bleeding
  • Concomitant use of medications that increase bleeding risk 2
• In patients with a history of gastrointestinal bleeding, consider co-administration of proton-pump inhibitors to minimize the risk of recurrent bleeding 1

Evidence-Based Outcomes

• Newer P2Y12 inhibitors (prasugrel and ticagrelor) are associated with significant reductions in mortality, reinfarction, and in-stent thrombosis compared to standard-dose clopidogrel in ACS patients 4
• The ISAR-REACT-5 trial found that prasugrel reduced rates of death, myocardial infarction, or stroke at 1 year compared with ticagrelor among patients with ACS undergoing PCI (9.3% vs 6.9%) with no significant difference in bleeding 3