Should a loading dose of antiplatelet agents be given to patients with Non-ST-Elevation Myocardial Infarction (NSTEMI) or unstable angina, and what are the recommended doses?

Loading Doses for NSTEMI and Unstable Angina

Yes, loading doses of antiplatelet agents should be given to patients with NSTEMI and unstable angina, consisting of aspirin 150-325 mg plus a P2Y12 inhibitor loading dose (clopidogrel 600 mg, prasugrel 60 mg, or ticagrelor 180 mg), with the specific P2Y12 inhibitor choice depending on whether an invasive or conservative strategy is selected and patient-specific contraindications. 1

Aspirin Loading Dose

• Administer aspirin 150-325 mg immediately upon hospital presentation in a chewable, non-enteric-coated form for rapid onset of action 1
• If oral administration is not possible, give intravenous aspirin 250-500 mg as an alternative 1
• Continue with maintenance dose of 75-160 mg daily indefinitely 1

P2Y12 Inhibitor Selection and Dosing

For Invasive Strategy (Early Angiography Planned)

The choice between P2Y12 inhibitors depends on timing and patient characteristics:

• Clopidogrel 600 mg loading dose can be given upstream (before angiography) or at the time of PCI 2

  • The 600 mg dose is preferred over 300 mg for more rapid and stronger platelet inhibition 1, 3
  • However, prasugrel should NOT be given until coronary anatomy is defined at angiography, as it cannot be used if CABG is needed 4

• Prasugrel 60 mg loading dose should be given promptly after coronary anatomy is established and a decision is made to proceed with PCI, no later than 1 hour after PCI 2, 4

  • Contraindicated in patients with prior stroke or TIA 4
  • Generally not recommended in patients ≥75 years or <60 kg due to increased bleeding risk 4
  • Consider 5 mg maintenance dose (instead of 10 mg) in patients <60 kg 4

• Ticagrelor 180 mg loading dose can be given upstream before angiography 2

  • When using ticagrelor, aspirin maintenance dose must not exceed 100 mg daily 1

For Conservative Strategy (No Early Angiography)

• Clopidogrel 300 mg loading dose followed by 75 mg daily should be added to aspirin and anticoagulant therapy as soon as possible after admission 2
• Continue for at least 1 month (Level of Evidence: A) and ideally up to 1 year (Level of Evidence: B) 2

Critical Timing Considerations

A key distinction exists between invasive and conservative strategies regarding when to load:

• For NSTEMI patients undergoing early invasive strategy, upstream loading with clopidogrel or ticagrelor is reasonable, but prasugrel must wait until anatomy is known 4
• The FDA label specifically notes that in the TRITON-TIMI 38 trial, prasugrel loading was not administered until coronary anatomy was established in UA/NSTEMI patients to avoid excessive bleeding risk in those requiring urgent CABG 4
• No clear benefit was observed when prasugrel loading dose was given prior to diagnostic angiography compared to at the time of PCI, but bleeding risk was increased with early administration 4

Evidence-Based Efficacy Considerations

• Recent data suggest prasugrel may be superior to ticagrelor in NSTE-ACS patients, with one 2020 randomized trial showing prasugrel reduced the combined 1-year risk of death, MI, and stroke (6.3% vs 8.7%, HR 1.41,95% CI 1.04-1.90) without increasing bleeding 5
• However, this finding requires confirmation, and the choice should account for contraindications (prior stroke for prasugrel) and patient-specific bleeding risk 5

Common Pitfalls to Avoid

• Do not give prasugrel upstream in NSTEMI/UA patients before knowing coronary anatomy, as this substantially increases bleeding risk if urgent CABG is needed 4
• Do not use enteric-coated aspirin for loading as it has delayed onset of action 1
• Do not exceed 100 mg daily aspirin maintenance dose when using ticagrelor, as higher doses reduce ticagrelor's efficacy 1
• Do not forget to screen for prior stroke/TIA before giving prasugrel, as this is an absolute contraindication 4
• In patients with history of gastrointestinal bleeding, co-administer proton-pump inhibitors with antiplatelet therapy to minimize recurrent bleeding risk 2