| Background: As an anti-paletet drug, Clopidogrel has been the mainstay of ACS(Acute Coronary Syndrome) treatment before and after PCI. And the treatment is very important to whether the patients can acquire long term benefit or not. However, the usage of clopidogrel following the guideline in different patients would lead to different effects, and it is found that clopidogrel resistance(CR)is associated with increased mortality in ACS patients with an increase in number of Stent Thrombosis and MI. The anti-platelet effect of clopidogrel, as a pro-drug, which metabolism is dependent on hepatic conversion of active metabolite through cytochrome P450 enzyme system. CYP2C19, which is a key member of P450 enzyme isozyme family, metabolize clopidogrel to the active metabolite. Some studies showed that the mutation of CYP2C19 gene could lead to decrease in production of the active metabolite of clopidogrel. And as a result the major adverse cardiovascular events increased. The test of CYP2C19 gene polymorphisms can be used to guide individual treatment and improve the effect of patient undergoing PCI. CYP2C19 gene polymorphisms have been reported mostly in west countries but rarely in China. Hence, the objective of this study is to explore the CYP2C19 gene polymorphisms, evaluate the anti-palete effect of treatment based on CYP2C19 genotype and accumulate more experience data for the clinical prastise.Objectives:To investigate the correlation between the distribution of description CYP2C19 polymorphism and the effect of anti-platelet therapy in patients with acute coronary symdrome disease after percutaneous coronary intervention( PCI).Methods:1.We selected 2117 patients diagnosed as coronary heart disease and treated with( PCI) in the Xijing Hospital. Gene polymophisms were analyzed in the Han population in northwest China. Based on the loss of function allele gene, the cases were divided into three genotype: fast metabolic genotype( *1/*1), intermediate metabolic genotype( *1/*2、*1/*3) and the slow metabolic genotype( *2/ *2、*2/*3、*3/* 3).There was statistically significant difference in the different regions,sexual distinction and different age groups of different CYP2C19 genotypes.2.Eight hundred and sixty-four cases with complete clinical data form the 2117 cases were divided into normal metabolic group(fast metabolic genotype, n = 346) and poor metabolic group(intermediate metabolic genotype and slow metabolic genotype, n= 461)and received anti-platelet therapy. The protocol was as follows: normal metabolic group was given oral clopidogrel 75 mg/d for 1 year and the poor metabolizer group was given clopidogrel 150 mg/d of intensive treatment in the first month and 75 mg/d form second month through the 12 th month. Major adverse cardiovascular events(MACE) incidences were recorded and compared 1, 3, 6, 9 and 12 months between groups.Inclusion criteria :①Patients who were hospitaled in Xi Jing Hospital and underwent Percutaneous Coronary Intervention( PCI) for ACS including ST-elevation and non-ST-elevation myocardial infarction( STEMI/NSTEMI), unstable angina(UA)from 2013 January to 2013 July;The diagnosis was performed according to ACS guideline. ②All operation were completed by the same surgeon;③The informed consent was signed voluntarily;④All the patients we selected were implanted 1-3 stents and clopidogrel was used for all the patients after operation.Exclusion criteria: ①Patients who were forbidden to take aspirin and clopidogrel. ②Patients who can not persist in taking antiplatelet drugs;③Patients who were lost of follow up during one year.Results:According to gene type, 885 cases(41.8%) were fast metabolic genotype, 971 cases(45.86%) were intermediary metabolism genotype, and 261 cases(12.32%) were slower metabolic genotype. Loss of follow-up was 36 cases and 21 cases respectively, in the normal metabolic group and poor metabolic group. For the effect of anti-platelet therapy, no statistically significant difference was observed in the incidence of MACE between normal metabolism group and poor metabolizer group.Logistic regression analysis showed that smoking,high low-density lipoprotein, old myocardial infarction were risk factors for MACE.Conclusion:The frequency of CYP2C19 allele mutation is high and mainly genotype *1 / *2 in patients after PCI. There was no statistically significant difference in the incidence of MACE between normal metabolic group and a poor metabolizer group after different doses of anti-platelet therapy. The one of effective ways which genotype guiding of PCI antiplatelet therapy might to be reduced major adverse cardiovascular events. |
PDF Full Text Request