What are the loading doses for P2Y12 inhibitors (such as clopidogrel, prasugrel, ticagrelor) in non-ST Elevation Myocardial Infarction (non-STEMI) management?

Loading Doses for P2Y12 Inhibitors in Non-STEMI Management

For patients with non-ST Elevation Myocardial Infarction (non-STEMI), the recommended loading doses are: clopidogrel 600 mg, prasugrel 60 mg, or ticagrelor 180 mg. 1

Specific P2Y12 Inhibitor Loading Doses

Clopidogrel

• Loading dose: 600 mg 1
• Maintenance dose: 75 mg daily
• Should be given as early as possible before or at the time of PCI 1
• Consider when ticagrelor or prasugrel are contraindicated or unavailable 1

Ticagrelor

• Loading dose: 180 mg 1
• Maintenance dose: 90 mg twice daily
• Should be given as early as possible before or at the time of PCI 1
• Preferred over clopidogrel in patients treated with an early invasive or ischemia-guided strategy 1

Prasugrel

• Loading dose: 60 mg 1, 2
• Maintenance dose: 10 mg daily (5 mg daily for patients <60 kg) 2
• Should be given promptly and no later than 1 hour after PCI once coronary anatomy is defined 1
• Contraindicated in patients with history of stroke or TIA 2
• Generally not recommended in patients ≥75 years due to increased bleeding risk 2

Timing of Loading Dose Administration

Early Invasive Strategy

• For patients undergoing an early invasive strategy, a loading dose of P2Y12 inhibitor should be given before the procedure 1
• Routine pre-treatment with a P2Y12 inhibitor is not recommended when coronary anatomy is unknown 1

Conservative (Ischemia-Guided) Strategy

• For patients managed with an initial conservative strategy, clopidogrel or ticagrelor (loading dose followed by daily maintenance dose) should be added to aspirin and anticoagulant therapy as soon as possible after admission 1

Special Considerations

High Bleeding Risk Patients

• In patients ≥75 years, prasugrel is generally not recommended due to increased bleeding risk 2
• For patients <60 kg, consider lower maintenance dose of prasugrel (5 mg daily) due to increased exposure to active metabolite 2
• Patients with history of stroke or TIA should not receive prasugrel 2

Aspirin Co-administration

• All patients should receive aspirin (162-325 mg non-enteric coated loading dose) 1
• The recommended maintenance dose of aspirin to be used with ticagrelor is 81 mg daily 1

Algorithm for P2Y12 Inhibitor Selection in Non-STEMI

1. First-line options (if no contraindications):

   • Ticagrelor 180 mg loading dose for most non-STEMI patients 1
   • Prasugrel 60 mg loading dose for patients undergoing PCI with no history of stroke/TIA and age <75 years 1, 2

2. Second-line option:

   • Clopidogrel 600 mg loading dose when ticagrelor or prasugrel are contraindicated, unavailable, or not tolerated 1

3. For elderly patients (≥70 years):

   • Consider clopidogrel as it may lead to fewer bleeding events without increasing ischemic events 3

Important Warnings and Precautions

• Avoid prasugrel in patients with history of stroke or TIA due to increased risk of cerebrovascular events 2
• Monitor for bleeding, especially in patients receiving prasugrel who are ≥75 years, <60 kg, or have other bleeding risk factors 2
• If possible, discontinue prasugrel at least 7 days prior to CABG surgery 2
• For patients requiring oral anticoagulation, carefully consider the bleeding risk when selecting P2Y12 inhibitor 4
• Crushing or chewing ticagrelor/prasugrel tablets may be considered when faster platelet inhibition is desired 5

By following these evidence-based recommendations for P2Y12 inhibitor loading doses in non-STEMI patients, clinicians can optimize antiplatelet therapy while balancing the risks of ischemic and bleeding events.