What is the loading dose for antiplatelet and anticoagulant medications in the management of myocardial infarction (heart attack)?

Loading Doses for Antiplatelet and Anticoagulant Therapy in Myocardial Infarction

Administer aspirin 162-325 mg orally (chewed, non-enteric coated) or 250-500 mg IV if oral route unavailable, plus a P2Y12 inhibitor loading dose (clopidogrel 600 mg, prasugrel 60 mg, or ticagrelor 180 mg) as early as possible in all patients with myocardial infarction, with anticoagulation using unfractionated heparin 70-100 U/kg IV bolus (or 50-70 U/kg if glycoprotein IIb/IIIa inhibitor planned) or bivalirudin 0.75 mg/kg IV bolus for patients undergoing PCI. 1, 2

Aspirin Loading Dose

• Give aspirin 162-325 mg orally immediately upon suspected MI diagnosis, using chewable non-enteric coated formulation for faster onset of action 1, 2
• If oral administration is impossible, use IV aspirin 250-500 mg as an alternative 1, 2
• Administer the loading dose even in patients already on chronic aspirin therapy, as research demonstrates that additional loading significantly reduces thromboxane A2-dependent platelet reactivity and corrects platelet hyperfunction present in over 50% of patients with STEMI on chronic aspirin 3, 4
• After loading, continue aspirin 75-100 mg daily indefinitely (use 81 mg daily when combined with ticagrelor) 1

P2Y12 Inhibitor Loading Doses

For STEMI with Primary PCI:

• Prasugrel 60 mg or ticagrelor 180 mg are preferred first-line agents over clopidogrel 1
• Clopidogrel 600 mg is acceptable when prasugrel or ticagrelor are unavailable, contraindicated, or not tolerated 1
• Administer loading dose as early as possible or at time of PCI 1

For STEMI with Fibrinolytic Therapy:

• Give clopidogrel 300 mg if age ≤75 years; give 75 mg (no loading dose) if age >75 years 1
• Prasugrel and ticagrelor are not recommended with fibrinolytic therapy 1

For NSTE-ACS:

• Clopidogrel 300-600 mg, prasugrel 60 mg, or ticagrelor 180 mg before or at time of angiography 1
• For conservative (non-invasive) strategy, clopidogrel loading dose should be given as soon as possible after admission 1
• Upstream administration (before angiography) may be considered if angiography timing anticipated >24 hours, though benefit is uncertain 1

Critical Dosing Considerations

Clopidogrel Dosing:

• 600 mg loading dose achieves more rapid and stronger platelet inhibition than 300 mg 1, 2
• The 300 mg dose was used in efficacy trials, but 600 mg is increasingly preferred for faster onset 1

Prasugrel Contraindications and Cautions:

• Absolutely contraindicated in patients with prior stroke or TIA 1, 5
• Generally not recommended in patients ≥75 years due to increased bleeding risk, except in high-risk situations (diabetes or prior MI) 5
• Consider 5 mg maintenance dose (instead of 10 mg) in patients <60 kg body weight 5
• Do not start in patients likely to undergo urgent CABG; discontinue at least 7 days before surgery if possible 5

Ticagrelor Specifics:

• Must use aspirin maintenance dose ≤100 mg daily (preferably 81 mg) when combined with ticagrelor 1, 2
• Loading dose 180 mg followed by 90 mg twice daily maintenance 1

Anticoagulant Loading Doses for PCI

Unfractionated Heparin:

• 70-100 U/kg IV bolus if no glycoprotein IIb/IIIa inhibitor planned 1
• 50-70 U/kg IV bolus if glycoprotein IIb/IIIa inhibitor planned 1
• Adjust additional boluses to maintain ACT 250-350 seconds (200-250 seconds with GP IIb/IIIa inhibitor) 1

Bivalirudin:

• 0.75 mg/kg IV bolus followed by 1.75 mg/kg/h infusion 1
• Additional 0.3 mg/kg bolus can be given if needed 1
• Preferred over heparin with GP IIb/IIIa inhibitor in patients at high bleeding risk 1
• Reduce infusion to 1 mg/kg/h if creatinine clearance <30 mL/min 1

Enoxaparin (if used):

• IV bolus followed 15 minutes later by first subcutaneous dose 1
• If age >75 years, omit IV bolus and start with reduced subcutaneous dose 1

Fondaparinux:

• Not recommended as sole anticoagulant for primary PCI 1
• May be used in conservative strategy: IV bolus followed 24 hours later by subcutaneous dose 1

Glycoprotein IIb/IIIa Inhibitors (Adjunctive)

These are Class IIa recommendations (reasonable to use in selected patients) 1:

• Abciximab: 0.25 mg/kg IV bolus, then 0.125 mcg/kg/min infusion (maximum 10 mcg/min) for 12 hours 1
• Eptifibatide: 180 mcg/kg IV bolus, then 2 mcg/kg/min; second 180 mcg/kg bolus 10 minutes after first (reduce infusion by 50% if CrCl <50 mL/min; avoid in hemodialysis) 1
• Tirofiban: 25 mcg/kg IV bolus, then 0.15 mcg/kg/min (reduce infusion by 50% if CrCl <30 mL/min) 1

Common Pitfalls to Avoid

• Do not use enteric-coated aspirin for loading dose due to delayed absorption 1, 2
• Do not withhold aspirin loading in patients already on chronic aspirin therapy, as platelet hyperfunction persists in many patients despite chronic therapy 3, 4
• Do not give prasugrel to patients with any history of stroke or TIA, as net harm occurs 1, 5
• Do not use fondaparinux as sole anticoagulant during PCI due to catheter thrombosis risk 1
• Do not exceed 100 mg daily aspirin maintenance when using ticagrelor, as higher doses reduce ticagrelor efficacy 1