Loading Doses for Myocardial Infarction Management
For patients with myocardial infarction (MI), a loading dose of 300-600 mg clopidogrel, 60 mg prasugrel, or 180 mg ticagrelor should be administered as early as possible or at the time of primary percutaneous coronary intervention (PCI), with the specific choice depending on patient characteristics and planned intervention. 1, 2
Antiplatelet Loading Doses by Agent
Clopidogrel
- For primary PCI in STEMI: 600 mg loading dose as early as possible or at time of PCI 1, 2
- For PCI after fibrinolytic therapy:
Prasugrel
- Loading dose: 60 mg as early as possible or at time of primary PCI 1, 2
- Timing: Should not be given sooner than 24 hours after administration of a fibrin-specific agent 1
- Contraindications: History of stroke or transient ischemic attack (TIA) 1, 3
Ticagrelor
- Loading dose: 180 mg as early as possible or at time of PCI 1
- Timing: Can be initiated on presentation or as soon as possible before or at the time of PCI 1
Anticoagulation During PCI
Unfractionated Heparin (UFH)
- With GP IIb/IIIa inhibitors: 50-70 U/kg IV bolus 1
- Without GP IIb/IIIa inhibitors: 70-100 U/kg IV bolus 1
Bivalirudin
- Loading dose: 0.75 mg/kg IV bolus 1
- Maintenance: 1.75 mg/kg/h infusion with or without prior UFH treatment 1
- Additional bolus: 0.3 mg/kg can be given if needed 1
- Dose adjustment: Reduce infusion to 1 mg/kg/h with estimated CrCl <30 mL/min 1
Special Considerations
Patient-Specific Factors
- Age ≥75 years: Prasugrel generally not recommended due to increased bleeding risk 3
- Weight <60 kg: Consider reducing prasugrel maintenance dose to 5 mg daily 3
- Prior stroke/TIA: Prasugrel is contraindicated 1, 3
- Timing before surgery:
Evidence on Higher Loading Doses
- The HORIZONS-AMI trial showed that patients receiving a 600 mg clopidogrel loading dose had significantly lower 30-day rates of mortality (1.9% vs 3.1%), reinfarction (1.3% vs 2.3%), and stent thrombosis (1.7% vs 2.8%) compared to those receiving 300 mg, without higher bleeding rates 4
- The ARMYDA-6 MI randomized study demonstrated that a 600 mg clopidogrel loading dose was associated with reduction in infarct size, improved angiographic results, better residual cardiac function, and fewer 30-day major adverse cardiovascular events compared to a 300 mg loading dose 5
Practical Algorithm for Loading Dose Selection
For STEMI patients undergoing primary PCI:
- First choice: Clopidogrel 600 mg loading dose OR
- Prasugrel 60 mg loading dose (if no history of stroke/TIA and age <75 years) OR
- Ticagrelor 180 mg loading dose
For patients receiving fibrinolytic therapy who later undergo PCI:
- If PCI ≤24 hours after fibrinolysis: Clopidogrel 300 mg loading dose
- If PCI >24 hours after fibrinolysis: Clopidogrel 600 mg loading dose
- Consider prasugrel only if >24 hours after fibrinolysis
For patients with high bleeding risk:
- Consider clopidogrel over prasugrel
- Consider bivalirudin over UFH with GP IIb/IIIa inhibitors 1
Common Pitfalls and Caveats
- Prasugrel should never be administered to patients with prior stroke or TIA due to increased risk of intracranial hemorrhage 1, 3
- Higher loading doses of antiplatelet agents increase bleeding risk, especially in elderly patients, those with low body weight, or those on concomitant anticoagulants 2
- Fondaparinux should not be used as the sole anticoagulant for primary PCI due to risk of catheter thrombosis 1
- Despite theoretical advantages, doubling the ticagrelor loading dose to 360 mg did not achieve faster or more intense platelet inhibition compared to standard prasugrel loading dose in STEMI patients 6