Influencing Factors Of Clopidogrel Efficacy And The Effect Of PON1 Gene Polymorphism On MACE Risk

Objective: To assess the efficacy of clopidogrel in Patients with acute coronary syndrome after PCI by thromboelastography.To determine the association between the PON1 Q192R(rs662)gene polymorphism and the risk of major adverse cardiovascular events(MACE),especially the risk of stent thrombosis(ST),in clopidogrel–treated patients with coronary heart disease(CHD): a systematic review and meta-analysisMethods: Platelet reactivity was detected by using thromboelastogram among patients taking aspirin 100mg/d and clopidogrel 75mg/d for 5 days.Univariate analysis was used to explore the effect of two-category variables and grade data on platelet inhibition rate.Spearman analysis was used to explore the correlation between platelet inhibition rate and continuous variables.We performed a systematic search of PubMed,the Cochrane library database for eligible studies.Articles meeting the inclusion criteria were comprehensively reviewed,and the available data were accumulated by systematic review the meta-analysis.Results: Clinical research shows,Diabetes(P=0.015)and CYP2C19*2(P=0.028)was the independent risk of platelet inhibition rate,hemoglobin(P=0.001)? white blood cell count(WBC)(P=0.002)?glomerular filtration rate(eGFR)(P=0.024)and stent length(P=0.040)were significant associated with platelet inhibition rate.Logistic regression analysis showed that diabetes(P=0.032),and PON1 Q carrying(P=0.02)were positively correlated with HTPR and were independent risk factors for HTPR;hemoglobin(Hb)(P=0.001))is a protective factor for HTPR.We identified 18 clinical trials with a total number of 16801 CHD patients,seven using a case–control design(n=3098)and eleven a prospective cohort design(n=13703).Meta-analysis revealed that the PON1 Q192R(rs662)genetic polymorphism was not associated with an increased risk of MACE [Q allele vs.R allele: 1.10(0.91-1.34),QQ vs.QR+RR: 1.08(0.83-1.40),QQ+QR vs.RR: 1.19(0.88-1.60),QQ vs.RR: 1.22(0.83-1.79),QQ vs.QR: 1.05(0.82-1.34),QQ+RR vs.QR: 0.98(0.79-1.22)] in CHD patients treated with clopidogrel.However,when difference in ethnicity was taken into account,significant influence of PON1 Q192R(rs662)genetic polymorphism on the risk of ST was observed in Caucasus patients under PON1 Q192R(rs662)dominant [QQ vs.QR+RR: 1.69(1.05-2.73),QQ vs.QR: 1.55(1.06-2.28)],but not in Asians.We identified 18 clinical trials with a total number of 16801 CHD patients,seven using a case–control design(n=3098)and eleven a prospective cohort design(n=13703).Meta-analysis revealed that the PON1 Q192R(rs662)genetic polymorphism was not associated with an increased risk of MACE [Q allele vs.R allele: 1.10(0.91-1.34),QQ vs.QR+RR: 1.08(0.83-1.40),QQ+QR vs.RR: 1.19(0.88-1.60),QQ vs.RR: 1.22(0.83-1.79),QQ vs.QR: 1.05(0.82-1.34),QQ+RR vs.QR: 0.98(0.79-1.22)] in CHD patients treated with clopidogrel.However,when difference in ethnicity was taken into account,significant influence of PON1 Q192R(rs662)genetic polymorphism on the risk of ST was observed in Caucasus patients under PON1 Q192R(rs662)dominant [QQ vs.QR+RR: 1.69(1.05-2.73),QQ vs.QR: 1.55(1.06-2.28)],but not in Asians.Conclusions: This study found that clinical factors such as diabetes,glomerular filtration rate,stent length,cellular factors such as hemoglobin level,white blood cell count,genetic factors such as CYP2C19*2 carrying,PON1 Q carrying,etc.may affect the efficacy of clopidogrel after PCI.Meta-analysis suggests that the PON1 Q192R(rs662)polymorphism has no major impact on the risk of MACE.However,PON1 192 QQ genotype may be a determinant of high risk of ST in Caucasus CHD patients receiving clopidogrel,but not in Asians.