Double-blind study of the safety of clopidogrel with and without a loadingdose in combination with aspirin compared with ticlopidine in combination with aspirin after coronary stenting - The Clopidogrel Aspirin Stent International Cooperative Study (CLASSICS)

Background-Combination therapy with the ADP receptor antagonist ticlopidine pins aspirin has emerged as standard care after coronary stenting. Clopido grel, a new ADP receptor antagonist, has greater molar potency than ticlopi dine and better safety/tolerability. Methods and Results Patients (n=1020) were randomized after successful sten t placement and initiated on a 28-day regimen of either (1) 300-mg clopidog rel loading dose and 325 mg/d aspirin on day 1, followed by 75 mg/d clopido grel 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 con sisted of major peripheral or bleeding complications, neutropenia, thromboc ytopenia or early discontinuation of study drug as the result of a noncardi ac adverse event during the study-drug treatment period. The primary end po int occurred in 9.1% of patients (n=31) in the ticlopidine group and 4.6% o f patients (n=31) in the combined clopidogrel group (relative risk 0.50; 95 % Cl 0.31 to 0.81; P=0.005). Overall rates of major adverse cardiac events (cardiac death, myocardial infarction, target lesion revascularization) wer e 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 superi or 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 an consistent with the hypothesis that clopidogrel and ticlo pidine have comparable efficacy with regard to cardiac events after success ful stenting.