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Objectives The aim of this study was to investigate the association between high on-treatment platelet reactivity (HPR) and the SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score (SS) for risk prediction of major adverse cardiovascular events (MACE) in patients with non–ST-segment elevation acute coronary syndrome (NSTEACS) undergoing percutaneous coronary intervention (PCI). Background Platelet function testing may be used to optimize antiplatelet therapy in high-risk patients, but identification of this category of patients remains challenging. Methods The GEPRESS (Gene Polymorphism, Platelet Reactivity, and the Syntax Score) study was a prospective, multicenter, observational study enrolling 1,053 patients with NSTEACS undergoing PCI and treated with clopidogrel. The platelet reactivity index (PRI) was measured at 3 time points: before PCI, at hospital discharge, and 1 month after PCI. Genetic variants of clopidogrel metabolism were determined in 750 patients. Patients were stratified by the presence of HPR (PRI >50%) and by tertile of the SS (upper SS tertile ≥15). The primary objective of this study was the risk of MACE in the period between 1 month and 1 year. Results Between 1 month and 1 year, 1-month HPR was an independent predictor of MACE in patients with an SS ≥15, but not in those with an SS <15, displaying a 5-fold increase in event rates (10.4% vs. 2.5%; p < 0.0001). CYP2C19*2 was the only single nucleotide polymorphism associated with HPR, but it was not associated with MACE. Although there was a significant variability in the PRI across the 1-month period, predischarge HPR and SS effectively stratified the risk of subsequent MACE up to 1-year follow-up. Conclusions In clopidogrel-treated patients with NSTEACS undergoing PCI, HPR was independently associated with an increased risk of MACE only in the presence of a high SS. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: The antiplatelet effect of standard or increased clopidogrel doses in patients with ST- segment elevation acute myocardial infarction (STEMI) has never been studied. In this study we compared the antiplatelet effect of a 75mg daily maintenance dose of clopidogrel with 150mg in patients with STEMI undergoing primary percutaneous coronary intervention (PCI). Materials and methods: Fifty-four patients with STEMI undergoing PCI were randomly allocated to receive either 75mg/day clopidogrel (group 1) or 150mg/day (group 2) for 1month. Platelet function, measured by 5 different assays, was determined at 3 time points: 38±8 hours after the procedure, 1week and 1month after randomization. Results: In group 1, mean ± SD platelet reactivity index (PRI) measured with the VASP assay was 57.7±15.7% and 46.9±15.7% at 1week and 1month, respectively, compared to 38.8±15.7% and 34.9±12.6% in group 2 (p=0.0001). Same results were observed for light transmittance aggregometry, whole blood aggregometry and VerifyNow, but not for thromboelastometry. In contrast to what may be expected, the 75mg daily maintenance dose took longer than 1-week to provide the full clopidogrel antiplatelet effect. Furthermore, patients in group 2 had a nearly 50% reduction in C-reactive protein levels both at 1week and 1month. Conclusion: In patients with STEMI and poor responsiveness to clopidogrel a 150mg daily maintenance dose of clopidogrel is associated with a significant reduction of platelet aggregation and a trend towards reduced inflammation. [Copyright &y& Elsevier]