| ObjectiveTo study the distribution of CYP2C19 gene polymorphism in patients with coronary heart disease in Shenyang and the effect of CYP2C19 gene polymorphism and risk factors of coronary heart disease on Clopidogrel Resistance.And retrospectively comparing the clinical effects of different antiplatelet regimens after PCI in CYP2C19 IM and PM patients with coronary heart disease to provide basis for rational use of antiplatelet drugs in patients with coronary heart disease.Methods1,957 patients with coronary heart disease were selected to investigate the distribution of CYP2C19 genotypes,which were wild type(fast metabolism,EM,* 1/ *1),fast metabolism(IM,*1/*2 or *1/*3),Slow Metabolites(PM,*2/*2,*2/*3 or *3/* 3).2,A total of 332 patients with coronary artery disease(PCI)were collected,who were treated with clopidogrel and aspirin in combination with conventional antiplatelet therapy.The patients’ genotype and platelet aggregation inhibition rate were observed.According to the inhibition rate,the patients were divided into clopidogrel resistance group(CR)and Non-resistance group(NCR),and analysis of CYP2C19 genotype on the impact of clopidogrel resistance.3,A total of 480 patients with CYP2C19 gene IM and PM type CHD undergoing PCI were collected and divided into routine treatment group(RT)and individualized treatment group(IT)acorrding to whether the patient is individualized on the basis of the CYP2C19 genotype.In the IT group,the CYP2C19 IM type patient using the clopidogrel dose doubling treatment method was set as the dose doubling group,and the CYP2C19 PM type patient using the ticagrelor treatment method was set as the ticagrelor group.Compareing the inhibition of platelet aggregation after treatment with the three groups of patients,and the occurrence of MACE and bleeding within 12 months.4,A total of 480 patients with CYP2C19 gene IM and PM type CHD undergoing PCI were collected.According to the patient’s different treatment plan after adjusting the medication,patients with IM type who used double doses of clopidogrel after adjusting the medication were dose-doubled and those who received ticagrelor after adjustment were given ticagrelor group.All patients were treated with conventional aspirin and clopidogrel dual antiplatelet therapy for 3 days after PCI.After that,the dose-doubling group doubled the clopidogrel dose,and the ticagrelor group used ticagrelor instead of clopidogrel.The blood platelet aggregation rate of the patients before and 3 days after the usual treatment and the adjusted individualized treatment for 3 days were collected.The decrease of the platelet aggregation rate before and after adjustment of the treatment plan was compared.Results1,The distribution frequency of CYP2C19 genotype in Shenyang *1/*1,*1/*2,*1/*3,*2/*2,*2/*3,*3/*3 were 41.17%,38.14%,7.42%,9.51%,3.13% and 0.63%.The total mutation genotype was 58.83%,of which the *1/*2 mutation had the highest genotype,and the rest of the genotypes were less than 10%.The frequencies of the alleles *1,*2,and *3 were 63.95%,30.15%,and 5.90%,respectively.The frequency of *2 mutations was higher,and the *3 genes were lower.The frequency of metabolic phenotypes EM,IM,and PM were 41.17%,45.56%,and 13.27%,respectively.Metabolomics of IM and PM accounted for 58.83% of the total metabolites,and the metabolomic frequency of IM was higher than that of EM metabolites.There was no significant difference in the frequency of CYP2C19 gene distribution between CHD patients in Shenyang and other regions(P <0.05).2,Factors affecting Clopidogrel Resistance in Patients with Coronary Heart Disease including age,intermediate metabolizer,poor metabolizer,the international standardization ratio,total cholesterol,lipoprotein,bile acid,the number of one-time stent≥2(P <0.05).3,The platelet aggregation rate and inhibition rate were compared between the different treatment groups before and after drug administration.The results showed that there was no difference in platelet aggregation rate between the treatment groups before treatment(P >0.05),and the platelet aggregation rate and inhibition rate were different between the groups after taking the drug.On the aggregation rate,the dose-doubling group and the ticagrelor group were smaller than the conventional treatment group(P <0.05),and the ticagrelor group was smaller than the dose-doubling group(P <0.05).The inhibitory rate was significantly higher in the dose-doubling group and the ticagrelor group than in the conventional treatment group(P <0.05).The ticagrelor group was significantly larger than the dose-doubling group(P <0.05).In terms of the incidence of MACE events,the proportion of recurrent myocardial infarctions was highest in all groups.The conventional treatment group was greater than the dose-doubling group and the ticagrelor group,and the difference was statistically significant(P <0.017).However,the incidence of recurrent myocardial infarction in the dose-doubling group and ticagrelor group was not statistically different(P >0.017).Except for recurrent myocardial infarction,there was no difference in the incidence of other MACE and bleeding events(P >0.017).4,The blood platelet aggregation rate of the patients in the double-dose group and the ticagrelor group before the medication was basically the same,and the difference was not statistically significant(P >0.05).After 3 days of conventional clopidogrel treatment,the platelet aggregation rate decreased in both groups,but it was not obvious.However,the platelet aggregation rate decreased significantly after adjusting the dose of the drug or switching to ticagrelor for individualized antiplatelet therapy for 3 days.The decrease of platelet aggregation rate in individualized treatment was greater than that of conventional therapy(P <0.05),and the decrease in patients in ticagrelor group was greater than that in dose-doubling group(P <0.05).Conclusions The polymorphism distribution of CYP2C19 gene in patients with coronary heart disease in Shenyang region has a high gene mutation rate and influences the occurrence of clopidogrel resistance.The use of CYP2C19 gene polymorphism to guide the use of antiplatelet drugs in patients with coronary heart disease after PCI has a good clinical effect.Clinical consideration should be given to the individual application of antiplatelet drugs based on the characteristics of patients with CYP2C19 genotypes. |
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