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

Loading Dose in Acute Myocardial Infarction

In acute MI, administer aspirin 162-325 mg orally (chewed, non-enteric coated) or 250-500 mg IV if unable to swallow, plus a P2Y12 inhibitor loading dose: prasugrel 60 mg, ticagrelor 180 mg, or clopidogrel 600 mg (300 mg if age >75 years with fibrinolysis), given as early as possible before angiography. 1, 2

Aspirin Loading Dose

• Administer 162-325 mg orally as the initial loading dose, preferably in chewable, non-enteric coated form to achieve rapid onset of antiplatelet action 1, 2
• If oral administration is not possible, give 250-500 mg IV as an alternative route 1
• The loading dose should be given even if the patient is already on daily aspirin therapy, as additional loading further reduces platelet hyperfunction and thromboxane B2 levels in acute MI 3
• Avoid enteric-coated aspirin for loading doses due to delayed absorption and slower onset of action 1, 2

Maintenance Dosing After Loading

• Continue with 75-100 mg daily (non-enteric coated) for long-term maintenance therapy 1, 2
• This low-dose maintenance exceeds the minimal effective dose for thromboxane A2 suppression while minimizing bleeding risk 1
• When using ticagrelor, aspirin maintenance dose should not exceed 100 mg daily, as higher doses were associated with reduced efficacy in the PLATO trial 1

P2Y12 Inhibitor Loading Dose

The choice depends on management strategy and patient characteristics:

For Primary PCI (Preferred Options)

• Prasugrel 60 mg loading dose (followed by 10 mg daily maintenance) is recommended for clopidogrel-naïve patients undergoing PCI 1

  • Use 5 mg daily maintenance if body weight <60 kg or age ≥75 years 1
  • Contraindicated in patients with prior stroke/TIA 1

• Ticagrelor 180 mg loading dose (followed by 90 mg twice daily) is recommended as an alternative first-line option 1

  • No dose adjustment needed for age or weight 1
  • May cause transient dyspnea in early treatment 1

• Clopidogrel 600 mg loading dose (followed by 75 mg daily) should be used when prasugrel or ticagrelor are unavailable, contraindicated, or not tolerated 1

  • The 600 mg loading dose achieves more rapid and stronger platelet inhibition compared to 300 mg 1
  • Standard 300 mg loading is acceptable but suboptimal for urgent situations 4

For Fibrinolytic Therapy

• Clopidogrel 300 mg loading dose if age ≤75 years 1
• Clopidogrel 75 mg initial dose (no loading) if age >75 years 1
• Prasugrel and ticagrelor have not been adequately studied with fibrinolytic therapy and should be avoided in this setting 1

Timing of Administration

• Administer both aspirin and P2Y12 inhibitor as early as possible, ideally before or at the time of angiography, not delayed until the catheterization laboratory 1, 2
• Early administration is consistent with pharmacokinetic data showing that oral antithrombotic agents require time to achieve therapeutic effect 1
• Clopidogrel without a loading dose delays establishment of antiplatelet effect by several days, which is unacceptable in acute MI 4

Evidence Quality and Nuances

The superiority of prasugrel and ticagrelor over clopidogrel is supported by large outcome trials (TRITON-TIMI 38 and PLATO), showing significant reductions in cardiovascular death, MI, and stroke 1, 5. However, prasugrel showed increased bleeding in elderly patients (≥75 years) and low body weight patients (<60 kg), necessitating dose reduction or alternative agent selection 1.

The 2025 ACC/AHA guidelines represent the most current evidence, confirming that double-dose clopidogrel (600 mg loading) does not provide additional benefit over standard dosing for the primary outcome but does reduce stent thrombosis in PCI patients 6. This supports using 600 mg loading when clopidogrel is chosen, particularly for PCI.

Common Pitfalls to Avoid

• Do not use 300 mg clopidogrel loading in primary PCI when 600 mg is available, as it provides suboptimal platelet inhibition 1
• Do not delay antiplatelet loading until angiography results are known, as early administration is critical 1
• Do not use prasugrel in patients with prior stroke/TIA due to increased bleeding risk without benefit 1
• Do not exceed 100 mg daily aspirin maintenance when using ticagrelor, as higher doses reduce efficacy 1
• Do not give prasugrel or ticagrelor with fibrinolytic therapy, as safety and efficacy are not established in this setting 1