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J Am Coll Cardiol, 2005; 45:1392-1396, doi:10.1016/j.jacc.2005.01.030
© 2005 by the American College of Cardiology Foundation
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CLINICAL RESEARCH: INTERVENTIONAL CARDIOLOGY

The Relation of Dosing to Clopidogrel Responsiveness and the Incidence of High Post-Treatment Platelet Aggregation in Patients Undergoing Coronary Stenting

Paul A. Gurbel, MD, FACC*, Kevin P. Bliden, BS, Kevin M. Hayes, DO, Jason A. Yoho, MD, William R. Herzog, MD, FACC and Udaya S. Tantry, PhD

Sinai Center for Thrombosis Research, Baltimore, Maryland

Manuscript received November 12, 2004; revised manuscript received December 20, 2004, accepted January 11, 2005.

* Reprint requests and correspondence: Dr. Paul A. Gurbel, Sinai Center for Thrombosis Research, Hoffberger Building, Suite 56, 2401 W. Belvedere Avenue, Baltimore, Maryland 21215 (Email: pgurbel{at}lifebridgehealth.org).

OBJECTIVES: We determined the effect of clopidogrel dosing on the incidence of nonresponsiveness (NR) and high post-treatment platelet aggregation (post-PA).

BACKGROUND: We have reported NR after a 300-mg loading dose. Limited information is available on the comparative effect of a 600-mg loading dose on the incidence of NR and high post-PA.

METHODS: Clopidogrel responsiveness and post-PA were measured in patients undergoing stenting (n = 190) randomly treated with either a 300-mg or a 600-mg clopidogrel load. Nonresponsiveness was defined as <10% absolute change in platelet aggregation, and high post-PA was defined as >75th percentile aggregation after 300 mg clopidogrel.

RESULTS: Nonresponsiveness was lower after 600 mg compared to the 300-mg dose (8% vs. 28% and 8% vs. 32% with 5 and 20 µM ADP, respectively, p < 0.001). Among the patients with high post-PA after 300 mg clopidogrel, 62% to 65% had NR, whereas after the 600-mg dose, all of the patients with high post-PA had NR.

CONCLUSIONS: A 600-mg clopidogrel loading dose reduces the incidence of NR and high post-PA as compared to a 300-mg dose. Higher dosing strategies and methods to confirm platelet inhibition should be further investigated in order to optimally use clopidogrel in patients undergoing stenting.

Abbreviations and Acronyms
  ADP = adenosine diphosphate
  GP = glycoprotein
  IR = intermediate responsiveness
  NR = nonresponsiveness
  post-PA = post-treatment platelet aggregation
  PPP = platelet poor plasma
  {Delta}A = absolute change in platelet aggregation




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