What is the loading dose of clopidogrel for Non-ST-Elevation Myocardial Infarction (NSTEMI)?

Clopidogrel Loading Dose for NSTEMI

For patients with Non-ST-Elevation Myocardial Infarction (NSTEMI), the recommended loading dose of clopidogrel is 300 to 600 mg, with 600 mg being preferred when percutaneous coronary intervention (PCI) is planned. 1

Recommended Loading Dose Regimens

• For NSTEMI patients for whom PCI is planned, clopidogrel 600 mg should be given as early as possible before or at the time of PCI (Level of Evidence: A) 1
• For NSTEMI patients in whom an initial conservative (non-invasive) strategy is selected, clopidogrel loading dose (300-600 mg) should be added to aspirin and anticoagulant therapy as soon as possible after admission 1
• The 600 mg loading dose achieves more rapid and greater platelet inhibition than the 300 mg dose, which is particularly important when urgent PCI is anticipated 2, 3

Clinical Evidence Supporting Higher Loading Dose

• The HORIZONS-AMI trial demonstrated that a 600 mg loading dose of clopidogrel compared to 300 mg resulted in lower 30-day rates of mortality (1.9% vs 3.1%), reinfarction (1.3% vs 2.3%), and stent thrombosis (1.7% vs 2.8%) without higher bleeding rates 3
• The CURRENT-OASIS 7 trial showed that in patients undergoing PCI, a double-dose clopidogrel regimen (600 mg loading dose) was associated with a significant reduction in stent thrombosis compared to standard dosing (300 mg loading dose) 4
• Higher loading doses (600 mg) achieve more rapid inhibition of platelet aggregation and a higher absolute level of inhibition compared to 300 mg 1, 5

Timing of Administration

• For patients undergoing an invasive strategy, clopidogrel should be administered as early as possible before or at the time of PCI 1
• If bivalirudin is selected as the anticoagulant, it is reasonable to omit upstream administration of a GP IIb/IIIa inhibitor if at least 300 mg of clopidogrel was administered at least 6 hours earlier than planned catheterization or PCI 1

Maintenance Dosing Following Loading Dose

• After the loading dose, clopidogrel should be continued at 75 mg daily for at least 12 months in NSTEMI patients undergoing PCI 1
• In high-risk patients not at increased risk of bleeding, a higher maintenance dose of 150 mg daily for 6 days following the loading dose, then 75 mg daily thereafter may be reasonable 1

Special Considerations and Cautions

• For patients with a history of stroke or transient ischemic attack, prasugrel is not recommended as part of dual antiplatelet therapy 1
• In patients ≥75 years of age or <60 kg, careful consideration of bleeding risk is needed when selecting higher loading doses 1, 6
• For patients likely to undergo urgent CABG, clopidogrel should be discontinued at least 5 days before surgery to reduce bleeding risk 1
• Patients who are CYP2C19 poor metabolizers may have reduced effectiveness with clopidogrel therapy 7

Alternative P2Y12 Inhibitors

• Prasugrel 60 mg loading dose or ticagrelor 180 mg loading dose are alternatives to clopidogrel in NSTEMI patients 1
• Ticagrelor 180 mg loading dose should be given as early as possible before or at the time of PCI 1
• When using ticagrelor, the recommended maintenance dose of aspirin is 81 mg daily 1

In conclusion, the evidence strongly supports using a 600 mg loading dose of clopidogrel for NSTEMI patients, particularly when PCI is planned, as this provides more rapid and potent platelet inhibition with improved clinical outcomes compared to the 300 mg dose.