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

Loading Dose for Myocardial Infarction

For acute MI, administer a loading dose of 162-325 mg of non-enteric-coated aspirin immediately, followed by clopidogrel (300-600 mg depending on timing of PCI and patient age). 1

Aspirin Loading Dose

The ACC/AHA guidelines establish 162-325 mg as the Class I recommendation for initial aspirin dosing in all MI patients. 1, 2

• The loading dose should be non-enteric-coated aspirin to ensure rapid absorption and immediate antiplatelet effect 1
• This dose achieves rapid thromboxane A2 inhibition, which is critical during the acute thrombotic phase of MI 1
• For patients unable to take oral medications, intravenous aspirin 250-500 mg can be administered 2

Evidence Supporting the 162-325 mg Range

• A large study of 48,422 STEMI patients treated with fibrinolytics found no mortality difference between 162 mg and 325 mg at 24 hours (2.8% vs 2.9%, p=0.894) or 7 days 3
• However, 325 mg was associated with significantly higher bleeding risk (adjusted OR 1.14,95% CI 1.05-1.24, p=0.003) compared to 162 mg 3
• Patients already on chronic aspirin who receive a loading dose (200-500 mg) during acute MI achieve sixfold greater thromboxane suppression compared to continuing 100 mg alone 4

Clopidogrel Loading Dose

The loading dose of clopidogrel depends on whether the patient is receiving fibrinolytic therapy and the timing of PCI: 1

For Patients Receiving Fibrinolytic Therapy:

• Age ≤75 years: 300 mg loading dose 1, 2
• Age >75 years: No loading dose, start with 75 mg daily 1

For Patients Undergoing PCI After Fibrinolysis:

• PCI within 24 hours: 300 mg loading dose (if not already given) 1
• PCI >24 hours after fibrinolysis: 600 mg loading dose (if not already given) 1

For NSTEMI/Unstable Angina:

• 300-600 mg loading dose 2

Prasugrel as Alternative

Prasugrel 60 mg loading dose is reasonable once coronary anatomy is known, but only if: 1

• PCI is performed >24 hours after fibrin-specific fibrinolytic therapy 1
• Patient has no history of prior stroke or TIA (absolute contraindication) 1

Anticoagulation Loading

For patients receiving fibrinolytic therapy, anticoagulation must be initiated concurrently: 1

Unfractionated Heparin (UFH):

• 60 U/kg IV bolus (maximum 4000 U) 1
• Followed by 12 U/kg/h infusion (maximum 1000 U/h initially) 1
• Adjust to maintain aPTT 1.5-2.0 times control (50-70 seconds) 1

Enoxaparin:

• Age <75 years: 30 mg IV bolus, then 1 mg/kg subcutaneously every 12 hours (maximum 100 mg for first 2 doses) 1
• Age ≥75 years: No bolus, 0.75 mg/kg subcutaneously every 12 hours (maximum 75 mg for first 2 doses) 1
• CrCl <30 mL/min: 1 mg/kg subcutaneously every 24 hours 1

Fondaparinux:

• 2.5 mg IV initial dose, then 2.5 mg subcutaneously daily 1
• Contraindicated if CrCl <30 mL/min 1
• Never use as sole anticoagulant for PCI due to catheter thrombosis risk 1, 2

Critical Timing Considerations

All loading doses should be administered as soon as the diagnosis of MI is established 2

• In acute STEMI, aspirin within the first 24 hours resulted in 23% relative risk reduction in 5-week vascular mortality (2.4% absolute risk reduction) 1
• The rapid antiplatelet effect is essential during the acute thrombotic phase when plaque rupture and superimposed thrombus formation are actively occurring 1

Common Pitfalls to Avoid

• Do not use enteric-coated aspirin for the loading dose, as delayed absorption negates the benefit of immediate platelet inhibition 1
• Do not give prasugrel to patients with prior stroke/TIA regardless of other factors 1
• Do not use fondaparinux alone during PCI without adding an anticoagulant with anti-IIa activity 1, 2
• Do not skip the loading dose in patients already on chronic aspirin therapy, as they still benefit from additional thromboxane suppression 4