Genotypes,Clopidogrel Response,and Outcomes In Chinese CAD Patients Undergoing PCI

Background:Genetic polymorphisms of key genes in clopidogrel metabolism pathway may contribute to the variability of the antiplatelet effect of clopidogrel in patients undergoing percutaneous coronary intervention(PCI),whereas the effects of these factors on clinical outcomes are controversial or unexplored.Objective:The aim of this study was to examine the associations among genetic polymorphisms,platelet reactivity,and clinical outcomes in Chinese patients undergoing PCI and treated with clopidogrel.Methods:A real-world prospective single-center cohort study was conducted in the First Affiliated Hospital of Nanjing Medical University.In-hospital patients with CAD and receiving stenting were consecutively screened.Patients who met the pre-specified inclusion and exclusion criteria were recruited.Arachidonic acid(AA)-and adenosine diphosphate(ADP)-induced platelet aggregations were detected by light transmission aggregometry.A total of 40 single nucleotide polymorphisms(SNPs)of 19 genes were investigated.Major adverse cardiovascular events(MACE)were defined as the composite of cardiovascular death,non-fatal myocardial infarction(MI),and ischemic stroke.In-hospital,1-month,6-month,and 12-month follow-ups were conducted.Results:A total of 2439 patients undergoing PCI and treated with clopidogrel were consecutively recruited.All participants were followed or suffered a MACE within the 1-year follow-up.MACE occurred in 69(2.83%)patients during the 1-year follow-up.No significant association was found between platelet reactivity and clinical outcomes,irrespectively of ADP-or AA-induced platelet aggregation(all P values>0.05).Among the 40 selected single nucleotide polymorphisms(SNPs),only A allele carriers of CYP2C19 rs4244285 showed a 2.19-fold(95%CI,1.08 to 4.43;P value = 0.030)risk of MACE as compared with non-A carriers.Besides,older age,MI presentation,higher SYNTAX score,higher serum creatinine,and lower left ventricular ejection fraction were also independent predictors(all P values<0.05).Conclusions:Among Chinese patients receiving PCI and clopidogrel for secondary prevention,CYP2C19 rs4244285 is an independent predictor of MACE within one year following PCI,whereas platelet reactivity did not show an association with clinical outcomes.