What is the recommended reloading dose of Plavix (clopidogrel) in the management of Acute Coronary Syndrome (ACS)?

Recommended Reloading Dose of Clopidogrel in Acute Coronary Syndrome Management

The recommended reloading dose of clopidogrel in patients with Acute Coronary Syndrome (ACS) is 600 mg, particularly for patients undergoing percutaneous coronary intervention (PCI) who have previously received a loading dose of clopidogrel. 1

Evidence-Based Recommendations for Clopidogrel Reloading

Initial Loading Dose

• For ACS patients who need an antiplatelet effect within hours, a 300 mg or 600 mg loading dose is recommended 2
• The 600 mg loading dose has a more rapid onset of action and more potent inhibitory effect compared to the 300 mg dose 1

Reloading Considerations

• Patients already on clopidogrel maintenance therapy (75 mg daily) who are readmitted for ACS or PCI benefit from reloading with 600 mg 1
• Patients undergoing PCI who have previously received a loading dose of 300 mg clopidogrel should receive another 300 mg loading dose 1
• The CURRENT-OASIS 7 trial demonstrated that a higher-dose regimen (600 mg loading dose followed by 150 mg daily for 7 days, then 75 mg daily) was beneficial in the PCI subgroup 1

Clinical Outcomes with 600 mg Reloading Dose

The CURRENT-PCI study (a subgroup analysis of CURRENT-OASIS 7) showed that in patients undergoing PCI:

• The double-dose clopidogrel regimen (600 mg loading, 150 mg daily for 7 days, then 75 mg daily) reduced cardiovascular death, MI, and stroke compared to standard dosing (4.5% vs 3.9%, p=0.039) 1
• The higher-dose regimen was associated with a small increase in major bleeding (1.6% vs 1.1%, p=0.009) 1

Special Considerations

• For STEMI patients undergoing primary PCI, prasugrel or ticagrelor should be preferred over clopidogrel when available 1
• For NSTE-ACS patients, ticagrelor (180 mg loading dose) is recommended over clopidogrel regardless of initial treatment strategy 1
• If switching from clopidogrel to ticagrelor, a loading dose of 180 mg ticagrelor is recommended irrespective of timing and loading dose of clopidogrel 1

Timing of Reloading

• Reloading should be administered as early as possible before or at the time of PCI 1
• The RELOAD study demonstrated that in patients on long-term clopidogrel therapy, a 900 mg reloading dose provided better platelet inhibition than 300 mg or 600 mg at 4 hours 3
• However, current guidelines and FDA labeling support the 600 mg dose as the standard reloading dose 1, 2

Cautions and Contraindications

• Increased bleeding risk with higher loading doses must be considered 1
• For patients requiring CABG, clopidogrel should be discontinued at least 5 days before surgery when possible 1
• Patients with high bleeding risk may require dose adjustment or alternative antiplatelet strategies 1

In conclusion, for patients with ACS who are already on clopidogrel maintenance therapy or who have received a previous loading dose and are undergoing PCI, a 600 mg reloading dose of clopidogrel is recommended based on current guidelines to achieve optimal platelet inhibition and improve clinical outcomes.