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European Heart Journal 2004 25(21):1903-1910; doi:10.1016/j.ehj.2004.07.036
Copyright © 2004 by the European Society of Cardiology.
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Clinical research

High clopidogrel loading dose during coronary stenting: effects on drug response and interindividual variability

Dominick J. Angiolilloa,*, Antonio Fernández-Ortizb, Esther Bernardob, Celia Ramírezb, Manel Sabatéb, Camino Bañuelosb, Rosana Hernández-Antolínb, Javier Escanedb, Raul Morenob, Fernando Alfonsob and Carlos Macayab

a Division of Cardiology, University of Florida, Shands Jacksonville, 655 West 8th Street, ACC Building, Jacksonville, FL 32209, USA
b Cardiovascular Institute, San Carlos, University Hospital, Madrid, Spain

Received April 29, 2004; revised July 26, 2004; accepted July 29, 2004 * Corresponding author. Tel.: +1-904 2443933; fax: +1-904 2443102 (E-mail: dominick.angiolillo{at}jax.ufl.edu).

AIM: To assess platelet inhibitory effects, interindividual variability in platelet inhibition as well as response to a 600 mg, compared to a standard 300 mg, clopidogrel loading dose (LD) after coronary stenting

METHODS AND RESULTS: Platelet function profiles were assessed in 50 patients undergoing coronary stenting receiving either a 300 mg (n=27) or 600 mg clopidogrel LD. ADP (6 μM) and collagen (6 μg/mL) induced platelet aggregation, as well as ADP (2 μM) induced glycoprotein (GP) IIb/IIIa activation and P-selectin expression were assessed at baseline and 4, 24, and 48 h following clopidogrel front-loading. A more intense and rapid inhibition of platelet activation (both GP IIb/IIIa activation and P-selectin expression) were achieved using a 600 mg, compared to a 300 mg, LD throughout the entire 48 hours (p<0.001). Although there were no differences in platelet aggregation, overall a 600 mg LD increased the number of clopidogrel responders and this was also achieved earlier compared to a 300 mg LD. A 600 mg LD did not reduce interindividual variability of platelet response.

CONCLUSION: The use of a 600 mg clopidogrel LD in patients undergoing coronary stenting optimises platelet inhibitory effects early after intervention and may provide a more effective protection against early thrombotic complications.


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