(Circulation. 2000;102:624.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Double-Blind Study of the Safety of Clopidogrel With and Without a Loading Dose in Combination With Aspirin Compared With Ticlopidine in Combination With Aspirin After Coronary Stenting
The Clopidogrel Aspirin Stent International Cooperative Study (CLASSICS)
From the Department of Cardiology, Hôpital Cardiologique, Lille, France (M.E.B.); Klinikum der Johannes-Gutenberg-Universität, Mainz, Germany (H.-J.R.); Division of Cardiology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland (P.U.); and Department of Cardiology, Glenfield General Hospital, Leicester, UK (A.H.G.).
Correspondence to Michel E. Bertrand, MD, Department of Cardiology B, Hôpital Cardiologique, 59037 Lille, France. E-mail mbcardio{at}ccub.internet.fr
Background—Combination therapy with the ADP receptor antagonist ticlopidine plus aspirin has emerged as standard care after coronary stenting. Clopidogrel, a new ADP receptor antagonist, has greater molar potency than ticlopidine and better safety/tolerability.
Methods and Results—Patients (n=1020) were randomized after successful stent placement and initiated on a 28-day regimen of either (1) 300-mg clopidogrel loading dose and 325 mg/d aspirin on day 1, followed by 75 mg/d clopidogrel and 325 mg/d aspirin; (2) 75 mg/d clopidogrel and 325 mg/d aspirin; or (3) 250 mg BID ticlopidine and 325 mg/d aspirin. The primary end point consisted of major peripheral or bleeding complications, neutropenia, thrombocytopenia, or early discontinuation of study drug as the result of a noncardiac adverse event during the study-drug treatment period. The primary end point occurred in 9.1% of patients (n=31) in the ticlopidine group and 4.6% of patients (n=31) in the combined clopidogrel group (relative risk 0.50; 95% CI 0.31 to 0.81; P=0.005). Overall rates of major adverse cardiac events (cardiac death, myocardial infarction, target lesion revascularization) were low and comparable between treatment groups (0.9% with ticlopidine, 1.5% with 75 mg/d clopidogrel, 1.2% with the clopidogrel loading dose; P=NS for all comparisons).
Conclusions—The safety/tolerability of clopidogrel (plus aspirin) is superior to that of ticlopidine (plus aspirin) (P=0.005). The 300-mg loading dose was well tolerated, notably with no increased risk of bleeding. Secondary end point data are consistent with the hypothesis that clopidogrel and ticlopidine have comparable efficacy with regard to cardiac events after successful stenting.
Key Words: aspirin • receptors • stents • thrombosis • ticlopidine
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