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Dose effect of clopidogrel reloading in patients already on 75-mg maintenance dose: the Reload with Clopidogrel
Jean-Philippe Collet1, Johanne Silvain, Antoine Landivier
1Institut de Cardiologie, Unité INSERM 856, Pitié-Salpêtrière University Hospital (AP-HP), Paris, France.
Circulation
|September 4, 2008
Summary
For patients on long-term clopidogrel, a 900 mg loading dose significantly improves residual platelet aggregation compared to 300 or 600 mg. This reduces poor or slow responses to antiplatelet therapy.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Clopidogrel loading doses are primarily studied in treatment-naïve patients.
- Optimal re-loading strategies for patients already on maintenance clopidogrel are not well-defined.
- This study investigates clopidogrel re-loading in patients with acute coronary syndromes or undergoing percutaneous coronary intervention.
Purpose of the Study:
- To evaluate the impact of different clopidogrel loading dose strategies on residual platelet aggregation.
- To determine the optimal loading dose of clopidogrel in patients already treated with maintenance therapy.
- To assess the effectiveness of a 900 mg clopidogrel loading dose in reducing suboptimal platelet inhibition.
Main Methods:
- 166 patients on long-term clopidogrel (75 mg/day) were randomized to receive initial loading doses of 300, 600, or 900 mg.
- A second loading dose was administered 4 hours later to ensure a total of 900 mg for all groups.
- Platelet aggregation was measured at baseline, 4 hours, and 24 hours using light transmission aggregometry and VerifyNow P2Y12.
Main Results:
- A significant stepwise increase in inhibition of residual platelet aggregation (IRPA) at 4 hours was observed with increasing initial loading doses (30.7% with 300 mg, 40.3% with 600 mg, 64.0% with 900 mg; P=0.0024).
- The rate of suboptimal response (IRPA <10% at 4 hours) was significantly lower with the 900 mg initial loading dose (5.3%) compared to 300 mg (23.6%) and 600 mg (20.4%).
- At 24 hours, IRPA did not differ significantly between the groups after the total 900 mg loading dose was administered.
Conclusions:
- In patients on long-term clopidogrel therapy, a 900 mg loading dose significantly enhances inhibition of residual platelet aggregation compared to 300 mg or 600 mg.
- A higher initial loading dose of 900 mg is more effective in reducing poor and/or slow responses to clopidogrel.
- These findings support the use of a 900 mg loading dose for patients requiring re-loading with clopidogrel.
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