title: Impact of gene polymorphisms, platelet reactivity, and the SYNTAX score on 1-year clinical outcomes in patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention: the GEPRESS study.
abstract: OBJECTIVE
  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.
authors.affiliation: Cardiovascular Department, Policlinico S. Orsola, Bologna, Italy. Electronic address: tulliopalmerini@hotmail.com.
authors.forename: Tullio
authors.initials: T
authors.lastname: Palmerini
authors.affiliation: Department of Cardiothoracic Science, Second University of Naples, A.O. dei Colli, Monaldi, Naples, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Calabrò
authors.affiliation: Department of Medicine and Surgery, University of Salerno, Salerno, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Piscione
authors.affiliation: Legnano Hospital, Legnano, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: De Servi
authors.affiliation: Department of Health Science, University of Milan, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Cattaneo
authors.affiliation: Cardiothoracic Department, Spedali Civili, Brescia, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Maffeo
authors.affiliation: Cardiology Division, Prato Hospital, Prato, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Toso
authors.affiliation: Monzino Heart Center, IRCCS, Milan, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Bartorelli
authors.affiliation: Department of Interventional Cardiology, Heart Hospital, Massa, Italy.
authors.forename: Cataldo
authors.initials: C
authors.lastname: Palmieri
authors.affiliation: Catheterization Laboratory, Azienda Ospedaliero-Universitaria Pisa, Pisa, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: De Carlo
authors.affiliation: Ferrarotto Hospital, University of Catania, Catania, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Capodanno
authors.affiliation: Cardiovascular Department, Policlinico S. Orsola, Bologna, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Barozzi
authors.affiliation: Cardiovascular Department, Policlinico S. Orsola, Bologna, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: Tomasi
authors.affiliation: Cardiovascular Department, Policlinico S. Orsola, Bologna, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Della Riva
authors.affiliation: Cardiovascular Department, Policlinico S. Orsola, Bologna, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Mariani
authors.affiliation: Cardiovascular Department, Policlinico S. Orsola, Bologna, Italy.
authors.forename: Nevio
authors.initials: N
authors.lastname: Taglieri
authors.affiliation: Cardiovascular Department, Policlinico S. Orsola, Bologna, Italy.
authors.forename: Letizia Bacchi
authors.initials: LB
authors.lastname: Reggiani
authors.affiliation: Department of Cardiothoracic Science, Second University of Naples, A.O. dei Colli, Monaldi, Naples, Italy.
authors.forename: Renatomaria
authors.initials: R
authors.lastname: Bianchi
authors.affiliation: Department of Advanced Biomedical Sciences, Università Federico II, Naples, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: De Rosa
authors.affiliation: Legnano Hospital, Legnano, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Mariani
authors.affiliation: Department of Health Science, University of Milan, Milan, Italy.
authors.forename: GianMarco
authors.initials: G
authors.lastname: Podda
authors.affiliation: Columbia University Medical Center and the Cardiovascular Research Foundation, New York, New York.
authors.forename: Philippe
authors.initials: P
authors.lastname: Généreux
authors.affiliation: Columbia University Medical Center and the Cardiovascular Research Foundation, New York, New York.
authors.forename: Gregg W
authors.initials: GW
authors.lastname: Stone
authors.affiliation: Department of Medicine/Division of Cardiology, University of Florida, Jacksonville, Florida.
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Angiolillo
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000000981:diagnostic imaging / Q000401:mortality / Q000628:therapy*; D000368:Aged; D001711:Biotransformation / Q000235:genetics; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D000077144:Clopidogrel; D017023:Coronary Angiography; D003328:Coronary Thrombosis / Q000097:blood / Q000209:etiology; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000097:blood / Q000209:etiology; D016017:Odds Ratio; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects* / Q000401:mortality; D010641:Phenotype; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010979:Platelet Function Tests; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine
keywords: SYNTAX score; clopidogrel; platelet reactivity