Association Of Cytochrome P4502C19Polymorphism With Cardiovascular Events In Patients With Coronary Artery Disease After Drug-eluting Stent Implantation

BackgroundDual antiplatelet treatment with clopidogrel and aspirin is currently the standardchoice for the prevention of thrombotic events in patients with acute coronarysyndromes (ACS) or those undergoing percutaneous coronary intervention (PCI) withstent implantation. Despite widespread prescription for patient care, there are stillsome cases experiencing the re-occurrence of adverse cardiovascular events, such asnonfatal myocardial infarction, stroke, stent thrombosis (ST) or sudden death.Thereare data suggesting that genetic variances in hepatic enzymes may affect clopidogrelresponsiveness and efficacy. The frequent genetic functional variant681G>A (*2)and636G>A (*3) of cytochrome P4502C19(CYP2C19) is an important contributorto the wide variability between individuals of the antiplatelet effect of clopidogrel.ObjectiveThis study aims to analyze the association of CYP2C19*2and CYP2C19*3lostof function allele and long-term prognosis of patients after drug-eluting stents (DES)implantation, so as to evaluate the significance of individualized antiplatelettreatment based on CYP2C19polymorphism.MethodsBetween May2012and May2013,248consecutive CAD patients in the firstaffiliated hospital of Guangzhou medical university were enrolled in this study.Among them,233patients regularly take clopidogrel for at least12month andaccomplish the follow-up. Clinical presentation: Stable angina,85cases; unstable angina,75cases; STEMI,58cases; NSTEMI:15cases.Using CYP2C19gene detection kit (DNA microarray chip method) to detectsingle nucleotide polymorphisms (SNPS) of CYP2C19gene681G> A (*2) and636G> A (*3) in selected patients. According to CYP2C19genotype, patients weredivided into Extensive Metabolizer (EM); Intermediary Metabolism (IM).and PoorMetabolism (PM).The patient’s follow-up was carried out through outpatient service, telephone andreadmission records. The study endpoint is1year Major Adverse Cardiac events(MACE) after PCI, including Cardiac death, Nonfatal myocardial infarction,Rehospitalization due to Unstable angina (UA), Target vascular Revascularization(TVR), In-stent restenosis/stent thrombosis(ST) and the composite end point ofMACE. Compare the incidence of MACE within1year among three groups andanalyzes the relationship between CYP2C19gene polymorphisms and MACE.Resultsamong the patients included into the study and follow-up,104patients areextensive metabolizers (EM), account for44.6%,110patients are intermediatemetabolizers (IM), account for47.2%,19patients are poor metabolizers, account for8.2%, The frequency of CYP2C19*1is68.1%, CYP2C19*2is28.0%, CYP2C19*3is3.9%.Result of clinical follow-up:3patient died (1in EM group,2in IM group)；7people caught by another myocardial infarction (1in EM group,2in IM group,4inPM group);26patients met with Rehospitalization due to UA (8in EM group,13inIM group,5in PM group);7patients needed TVR (2in EM group,5in IM group);5patients encountered In-stent restenosis or ST (2in EM group,3in IM group).There are differences in the incidence of nonfatal myocardial infarction as wellas composite end point of MACE among three groups by Person chi-square test (P <0.05). However, no significant difference was observed in the incidence of the restsingle event among three groups. At the same time, the incidence of the compositeend point of MACE was higher in CYP2C19*2or*3allele carriers (IM+PM group) when compared with non-carriers (EM)(20.9%vs10.6%), P=0.033. Using Logisticregression model to analyze the related factors influencing the MACE and found therewas a correlation between CYP2C19polymorphisms and MACE (P=0.026;95%CI,1.118to5.691, OR=2.522).ConclusionCytochrome P4502C19*2or*3allele loss of function carriers have increasedincidence of adverse cardiovascular events, CYP2C19polymorphism is related toclinical outcomes of coronary heart disease patients receiving clopidogrel afterdrug-eluting stent implantation.