The TRITON-TIMI 38 platelet substudy shows that prasugrel results in greater inhibition of ADP-mediated platelet function in ACS patients than clopidogrel, supporting the hypothesis that greater platelet inhibition leads to a lower incidence of ischaemic events and more bleeding both early and late following PCI.

Background-In the prospective randomized Clinical Evaluation of the Xience V Everolimus Eluting Coronary Stent System in the Treatment of Patients with de novo Native Coronary Artery Lesions (SPIRIT) III trial, an everolimus-eluting stent (EES) compared with a widely used paclitaxel-eluting stent (PES) resulted in a statistically significant reduction in angiographic in-segment late loss at 8 months and noninferior rates of target vessel failure (cardiac death, myocardial infarction, or target vessel revascularization) at 1 year. The safety and efficacy of EES after 1 year have not been reported. Methods and Results-A total of 1002 patients with up to 2 de novo native coronary artery lesions (reference vessel diameter, 2.5 to 3.75 mm; lesion length Յ28 mm) were randomized 2:1 to EES versus PES. Antiplatelet therapy consisted of aspirin indefinitely and a thienopyridine for Ն6 months. Between 1 and 2 years, patients treated with EES compared with PES tended to have fewer episodes of protocol-defined stent thrombosis (0.2% versus 1.0%; Pϭ0.10) and myocardial infarctions (0.5% versus 1.7%; Pϭ0.12), with similar rates of cardiac death (0.3% versus 0.3%; Pϭ1.0) and target vessel revascularization (2.9% versus 3.0%; Pϭ1.0). As a result, at the completion of the 2-year follow-up, treatment with EES compared with PES resulted in a significant 32% reduction in target vessel failure (10.7% versus 15.4%; hazard ratio, 0.68; 95% confidence interval, 0.48 to 0.98; Pϭ0.04) and a 45% reduction in major adverse cardiac events (cardiac death, myocardial infarction, or target lesion revascularization; 7.3% versus 12.8%; hazard ratio, 0.55; 95% confidence interval, 0.36 to 0.83; Pϭ0.004). Among the 360 patients who discontinued clopidogrel or ticlopidine after 6 months, stent thrombosis subsequently developed in 0.4% of EES patients versus 2.6% of PES patients (Pϭ0.10). Conclusions-Patients treated with EES rather than PES experienced significantly improved event-free survival at a 2-year follow-up in the SPIRIT III trial, with continued divergence of the hazard curves for target vessel failure and major adverse cardiac events between 1 and 2 years evident. The encouraging trends toward fewer stent thrombosis episodes after 6 months in EES-treated patients who discontinued a thienopyridine and after 1 year in all patients treated with EES rather than PES deserve further study. (Circulation. 2009;119:680-686.)

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