Loading Dose for Plavix (Clopidogrel)
For acute coronary syndrome (ACS), administer a 300–600 mg oral loading dose of clopidogrel as soon as possible, followed by 75 mg daily maintenance. 1, 2
Standard Loading Dose Recommendations
Acute Coronary Syndrome (STEMI and NSTEMI)
The FDA-approved loading dose is 300 mg, which is the most extensively studied regimen in clinical trials. 3, 2
A 600 mg loading dose achieves faster and more complete platelet inhibition than 300 mg and is recommended by current guidelines, particularly for patients undergoing percutaneous coronary intervention (PCI). 4, 1
Both 300 mg and 600 mg loading doses are acceptable, but 600 mg provides superior platelet inhibition within 4 hours and reduces the incidence of major adverse cardiovascular events (MACE). 4, 5
The antiplatelet effect appears within 90 minutes of a 300 mg loading dose, with full antiplatelet effects equivalent to 10 days of maintenance therapy achieved by 6 hours. 6
Age-Specific Considerations
For patients younger than 75 years with ACS, use either 300 mg or 600 mg loading dose. 1, 3
For patients 75 years or older receiving fibrinolytic therapy for STEMI, omit the loading dose entirely and start directly with 75 mg daily maintenance due to increased bleeding risk. 1, 6
For patients 75 years or older undergoing primary PCI (without fibrinolysis), the optimal loading dose has not been established, but 300 mg is generally preferred over 600 mg to balance efficacy and bleeding risk. 3
Timing of Administration
Administer the loading dose as early as possible when ACS is suspected or confirmed, ideally before coronary angiography. 1, 3
For elective PCI, give 600 mg at least 2 hours before the procedure, or 300 mg at least 6 hours before, to ensure adequate platelet inhibition at the time of intervention. 1
Pre-treatment with clopidogrel (median 10 days prior to PCI in the CURE trial) reduced cardiovascular events by approximately 31% compared to loading at the time of intervention. 3
Context-Specific Dosing
Primary PCI for STEMI
- Administer at least 300 mg loading dose, preferably 600 mg, as soon as possible before or at the time of catheterization. 4
Fibrinolytic Therapy for STEMI
Give 300 mg loading dose at the time of fibrinolytic administration for patients younger than 75 years. 1, 6
No loading dose for patients 75 years or older; start with 75 mg daily. 1, 6
Patients Already on Clopidogrel Maintenance
If a patient has been on 75 mg daily maintenance for at least 7 days and presents with ACS or requires urgent PCI, administer an additional 300–600 mg loading dose. 4, 7
A 900 mg reload in patients already on maintenance therapy provides superior platelet inhibition compared to 300 mg or 600 mg, with significantly fewer suboptimal responders (5.3% vs. 23.6%). 7
Maintenance Therapy
Continue 75 mg once daily for at least 12 months after ACS or stent implantation unless bleeding risk outweighs benefit. 4, 1, 3
For bare-metal stents, maintain therapy for a minimum of 1 month, ideally up to 12 months. 1
For drug-eluting stents, maintain therapy for at least 12 months. 4, 1
Bleeding Risk Considerations
Dual antiplatelet therapy (clopidogrel plus aspirin) increases major bleeding by approximately 1% (from 2.7% to 3.7%) compared to aspirin alone, but this is offset by a ~20% reduction in cardiovascular death, MI, and stroke. 1
The CURRENT-OASIS 7 trial showed that double-dose clopidogrel (600 mg loading, 150 mg daily for 6 days) increased major bleeding (2.5% vs. 2.0%) without significant benefit in the overall ACS population, though it reduced stent thrombosis in the PCI subset. 4, 8
Peri-Operative Management
Discontinue clopidogrel 5–7 days before elective coronary artery bypass grafting (CABG) to reduce surgical bleeding risk. 1, 3
Patients who undergo CABG within 5–7 days of the last clopidogrel dose experience increased bleeding, though the overall risk remains modest. 3
Common Pitfalls
Avoid using enteric-coated aspirin with clopidogrel loading, as it delays onset of antiplatelet effect; use chewable or intravenous aspirin instead. 4
Do not use strong CYP2C19 inhibitors (omeprazole, esomeprazole) concomitantly, as they diminish clopidogrel's antiplatelet effect. 1
In patients with prior stroke or TIA, clopidogrel remains acceptable, whereas prasugrel is contraindicated. 1