What are the loading doses of medications used in the management of myocardial infarction (heart attack)?

Loading Doses of Medications in Myocardial Infarction

All patients with suspected myocardial infarction should receive aspirin 162-325 mg loading dose immediately (chewable or IV if unable to swallow), followed by a P2Y12 inhibitor loading dose (clopidogrel 600 mg, prasugrel 60 mg, or ticagrelor 180 mg) as early as possible or at the time of PCI. 1, 2

Antiplatelet Therapy Loading Doses

Aspirin

• Loading dose: 162-325 mg (chewable formulation preferred for faster absorption) or 250-500 mg IV if oral administration not possible 1, 2, 3
• Administer immediately when MI diagnosis is deemed probable, before any other interventions 1, 3
• Continue indefinitely at maintenance dose of 81 mg daily (preferred) or 81-325 mg daily 1, 2

P2Y12 Inhibitor Loading Doses

Clopidogrel:

• Primary PCI: 600 mg loading dose before or at time of PCI for more rapid and potent platelet inhibition 1, 2
• Post-fibrinolytic PCI timing matters:
  • If PCI ≤24 hours after fibrinolysis: 300 mg loading dose 1, 2
  • If PCI >24 hours after fibrinolysis: 600 mg loading dose 1, 2
  • If already received loading dose with fibrinolytic: continue 75 mg daily without additional loading 1, 2
• Maintenance: 75 mg daily for at least 12 months 1, 2

Prasugrel:

• Loading dose: 60 mg once coronary anatomy is known 1, 2, 4
• Timing restriction: Do not give sooner than 24 hours after fibrin-specific fibrinolytic or 48 hours after non-fibrin-specific agent 1
• Maintenance: 10 mg daily (consider 5 mg daily if weight <60 kg) 2, 4
• Absolute contraindication: Prior stroke or TIA 1, 4
• Generally not recommended in patients ≥75 years due to increased bleeding risk 4

Ticagrelor:

• Loading dose: 180 mg as early as possible or at time of primary PCI 2
• Maintenance: 90 mg twice daily 2

Anticoagulation Loading Doses

Unfractionated Heparin (UFH)

• Loading dose: 100 U/kg IV bolus (or 60 U/kg if GP IIb/IIIa inhibitor planned) 1
• Additional boluses as needed during PCI to maintain therapeutic ACT 1
• Target ACT: 250-300 seconds (HemoTec) or 300-350 seconds (Hemochron) without GP IIb/IIIa 1

Enoxaparin

• Loading dose: 30 mg IV bolus, followed 15 minutes later by 1 mg/kg subcutaneous 1, 3
• Age >75 years: No IV bolus, start with reduced subcutaneous dose 1
• For PCI after enoxaparin: No additional dose if last dose within 8 hours; 0.3 mg/kg IV bolus if 8-12 hours since last dose 1

Fondaparinux

• Loading dose: 2.5 mg IV bolus, followed 24 hours later by subcutaneous dose 1
• Critical caveat: Cannot be used as sole anticoagulant for PCI - requires additional anti-IIa agent due to catheter thrombosis risk 1

Fibrinolytic Therapy Loading Doses (When PCI Not Available Within 120 Minutes)

Tenecteplase (TNK-tPA) - Single IV bolus based on weight: 1, 3

• <60 kg: 30 mg
• 60 to <70 kg: 35 mg
• 70 to <80 kg: 40 mg
• 80 to <90 kg: 45 mg
• ≥90 kg: 50 mg

Alteplase (t-PA): 1

• 15 mg IV bolus
• Then 0.75 mg/kg over 30 minutes
• Then 0.5 mg/kg over 60 minutes
• Maximum total dose: 100 mg

Reteplase (r-PA): 1

• 10 U IV bolus + 10 U IV bolus 30 minutes apart

Streptokinase: 1

• 1.5 million units over 30-60 minutes IV

Glycoprotein IIb/IIIa Inhibitors

• Consider abciximab, high-bolus-dose tirofiban, or double-bolus eptifibatide at time of primary PCI in selected patients receiving UFH 2
• Dosing is weight-adjusted and specific to each agent

Critical Timing and Sequencing

Optimal medication sequence: 3

1. Aspirin immediately upon diagnosis
2. Clopidogrel as soon as possible after aspirin
3. Anticoagulation (enoxaparin or UFH) before reperfusion therapy
4. Fibrinolytic (if applicable) or proceed to PCI
5. Additional P2Y12 loading at PCI if not previously given

Important Caveats and Pitfalls

Bleeding Risk Factors: 4

• Weight <60 kg requires dose reduction (prasugrel 5 mg maintenance)
• Age ≥75 years has increased bleeding risk, especially with prasugrel
• Prior stroke/TIA is absolute contraindication to prasugrel 1, 4

Surgical Considerations: 2, 4

• Discontinue clopidogrel/ticagrelor at least 5 days before CABG (preferably 7 days)
• Discontinue prasugrel at least 7 days before CABG
• Do not start prasugrel if urgent CABG likely 4

Drug Interactions: 1

• Discontinue NSAIDs and COX-2 inhibitors immediately - they increase risk of death and reinfarction

Premature Discontinuation: 2

• Stopping P2Y12 inhibitors early significantly increases stent thrombosis risk
• Continue dual antiplatelet therapy for minimum 12 months after stenting