Time dependence of platelet inhibition after a 600-mg loading dose of clopidogrel in a large, unselected cohort of candidates for percutaneous coronary intervention

Background - Pretreatment with clopidogrel can reduce the risks associated with percutaneous coronary intervention ( PCI). To shorten the time for clopidogrel to become effective, a 600- mg loading dose has been used. We sought to validate this regimen in a large cohort and investigated the time dependence of the antiplatelet effect of 600 mg of clopidogrel. Methods and Results - Our study included 1001 patients who were scheduled for cardiac catheterization as potential candidates for PCI. We obtained blood samples before administration of 600 mg of clopidogrel and at the time of catheterization, which varied according to logistic needs. We assessed platelet aggregation by optical aggregometry and surface expression of P- selectin and activated glycoprotein IIb/ IIIa by flow cytometry. Platelet aggregation induced by 5 mu mol/ L ADP was 51 +/- 14% when catheterization was performed at < 1 hour, 41 +/- 14% at 1 to < 2 hours, 37 +/- 15% at 2 to < 4 hours, 36 +/- 13% at 4 to < 6 hours, and 35 +/- 14% at >= 6 hours after clopidogrel administration. After 2 hours ( n = 718), the level of platelet aggregation and the surface expression of P- selectin and activated glycoprotein IIb/ IIIa did not change significantly with time after clopidogrel ( P > 0.24 by univariate or multivariate regression). Comedication with CYP3A4 metabolized statins did not significantly affect platelet aggregation after clopidogrel ( P = 0.62). Among the 428 patients undergoing PCI, the 30- day composite rate of major adverse cardiac events was 1.9%, with no significant difference between patients undergoing PCI within 2 hours after clopidogrel loading and those undergoing PCI at a later time point. Conclusions - After loading with 600 mg of clopidogrel, the full antiplatelet effect of the drug is achieved after 2 hours. Statins do not interfere with the level of platelet inhibition after this dose.