Benefit of clopidogrel according to timing of percutaneous coronary intervention in patients with acute coronary syndromes: Further results from the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) study

Background The CURE study demonstrated the benefit of clopidogrel in patients with non-ST elevation (NSTE) acute coronary syndromes (ACSs), including those undergoing percutaneous coronary intervention (PCI). It did not report the relation between clopidogrel and timing of PCI or, more specifically, the role of clopidogrel in patients managed with an early interventional strategy, the current preferred treatment option for patients with NSTE ACSs. In the present study, we examined the relation between clopidogrel therapy, timing of PCI, and cardiovascular (CV) events in patients participating in the CURE study. Methods A total of 12562 patients with NSTE ACSs was randomized in double-blind fashion to clopidogrel or placebo (300 mg loading dose, then 75 mg/d) in addition to aspirin for up to 1 year. We analyzed the data of the 2658 CURE patients undergoing PCI and related the incidence of outcome events (CV death/myocardial infarction [MI]) to timing of PCI after randomization: early (<48 hours, median 1.0 day, n = 370), intermediate (>= 48 hours to initial hospital discharge, median 6.8 days, n = 1360), and late (after initial hospital discharge, median 47.6 days, n = 928). Results Clopidogrel showed consistent treatment benefit over the 12-month (mean 9 months) follow-up period irrespective of timing of PCI (relative risk [RR] 0.53 for the early group, RR 0.72 for the intermediate group, RR 0.70 for the late group). After adjustment for propensity to undergo PCI, the greatest treatment benefit of clopidogrel was observed in patients undergoing PCI <48 hours after randomization (RR 0.45, 95% CI 0.21-0.96, P =.038), although with overlap between groups. The lowest absolute event rate (6.7% CV death/MI) was observed in patients treated with clopidogrel and undergoing PCI within 48 hours. There was no increased risk of major bleeding in the early PCI group. Conclusions The benefit of therapy with clopidogrel in addition to aspirin in patients presenting with NSTE ACSs was significant irrespective of the timing of PCI. The combination of clopidogrel and an early (<48 hours) interventional strategy was associated with low absolute event rates for CV death/nonfatal MI.