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

JACC Cardiovasc Interv. 2014 Oct;7(10):1117-27. doi: 10.1016/j.jcin.2014.04.020. Epub 2014 Sep 17.

Abstract

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.

Keywords: SYNTAX score; clopidogrel; platelet reactivity.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / blood
  • Acute Coronary Syndrome / diagnostic imaging
  • Acute Coronary Syndrome / mortality
  • Acute Coronary Syndrome / therapy*
  • Aged
  • Biotransformation / genetics
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Clopidogrel
  • Coronary Angiography*
  • Coronary Thrombosis / blood
  • Coronary Thrombosis / etiology
  • Cytochrome P-450 CYP2C19 / genetics*
  • Cytochrome P-450 CYP2C19 / metabolism
  • Female
  • Genotype
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Myocardial Infarction / blood
  • Myocardial Infarction / etiology
  • Odds Ratio
  • Percutaneous Coronary Intervention / adverse effects*
  • Percutaneous Coronary Intervention / mortality
  • Phenotype
  • Platelet Aggregation Inhibitors / pharmacokinetics
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Platelet Function Tests*
  • Polymorphism, Genetic*
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Assessment
  • Risk Factors
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / pharmacokinetics
  • Ticlopidine / therapeutic use
  • Time Factors
  • Treatment Outcome

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Ticlopidine