Effect Of Triple Antiplatelet Therapy On Aggregation Of Platelet In Patients With CYP2C19Genetic Mutation Undergoing Percutaneous Coronary Intervention

Objective:To determine the Platelet reactivity effect of adding cilostazol to standard-dose clopidogrel triple antiplatelet in cytochrome P450(CYP)2C19loss-of-function allelet patients undergoing pecutaneous coronary intervention by thromboelastography(TEG).Methods:A total of262patients with coronary heart disease undergoing percutaneous coronary intervention between March2013to March2014in our department of cardiology were enrolled in this study.2ml blood of antecubital vein from all patients were detected genotypes of CYP2C19after percutaneous coronary intervention. According to the missing of allelic gene, genotypic of CYP2C19was classified as:wild type*1/*1> heterzygousmutant type*1/*2>*1/*3and homozygousmutant type*2/*2>*2/*3>*3/*3. the patients with heterzygousmutant type*1/*2,*l/*3and homozygousmutant type*2/*2,*2/*3>*3/*3were divided into three subgroups. We excluded27patients.The number of the patients of the standard dual antiplatelet group was42,The number of the patients of the double-dose of clopidogrel group was39, The number of the patients of the cilostazol plus standard dual antiplatelet group was41.Platelet aggregatation rate induced by5umol/L ADP were measured by throambelastography(TEG) in48hours after stenting and the seventh day after taking this medicine,respectively. Then,analyzed all measure value by using the17.0SPSS software.Results:(1) The number and proportion of wild type (*1/*1) was113and43.1%,respectively;while heterozygous mutant type (*1/*2>*1/*3) was115and43.9%,respectively;and homozygous mutant type (*2/*2,*2/*3,*3/*3)was34and13%,respectively.(2) The rate of clopidogrel resistance was68.9%in patients carried the allelic genie mutation of CYP2C19polymorphism.(3) The levels of Platelet aggregatation rate induced by5umol/L ADP were lower in patients with the double-dose of clopidogrel group than the standard dual antiplatelet group at the seventh day after taking this medicine (P=0.102, P>0.05). There is no significant difference.(4)The levels of Platelet aggregatation rate induced by5umol/L ADP were lower in patients with the cilostazol plus standard dual antiplatelet group than the standard dual antiplatelet group at the seventh day after taking this medicine(P=0.004,P<0.01). There is significantly significant difference.(5)The levels of Platelet aggregatation rate induced by5umol/L ADP were significantly lower in patients with the cilostazol plus standard dual antiplatelet group than the double-dose of clopidogrel group at the seventh day after taking this medicine(P=0.223^P>0.05). There is no significant difference.Conclusions:(1)The proportion of patients carried the CYP2C19loss-of-function allele (*2or*3) was56.9%; similar with the prevalence of CYP2C19gene mutations reported in the domestic and foreign studies.(2)The rate of clopidogrel resistance was68.9%in patients carried the CYP2C19loss-of-function allele (*2or*3).(3)Adjuctive cilostazol to dual antiplatelet therapy can achieve consistently intensified platelet inhibition in patients with carried the CYP2C19loss-of-function allele undergoing coronary intervention.(4) Diabates mellitus can be used as independent predictive factors to predicted the rate of clopidogrel resistance in patients with carried the CYP2C19loss-of-function allele. This paper contains7Figures,10Tables and54References.