Study Of Pharmacokineticsand Pharmacodynamicsof Clopidogrel And Outcomes Of Patients Undergoing PCI

Objective:To investigate the risk factors of clopidogrel resistance and ischemic events in patients undergoing percutaneous coronary intervention(PCI).Method:A total of 490 Chinese patients with coronary artery disease(CAD)who received PCI were recruited in this study.Blood samples were collectedfromcubitalveins after administrated clopidogrel for 5days for platelet aggregation function test anddeterminatingconcentration of clopidogrel and its active metabolite(CAMD)inhuman blood.5μM adenosine diphosphate(ADP)-induced platelet aggregations(PLADP)were determined using the light transmission aggregometer(LTA).Clopidogrel low response(CLR)was defined as PLADP>40%.Liquid chromatography-tandem mass spectrometry(LC-MS/MS)was used to detect concentration for clopidogrel and CAMD in plasma.All the recruited patients were visited by outpatient or telephone and major adverse cardiovascular events(MACE)like death,non-fatal MI,stent thrombosis and strokewererecorded during 1 year.Data were analyzed using independent sampleT-test,chi-square and logistic regression analysisusing the SPSS software 22.0.Result:In total of 490 patients,80 of them(16.3%)were low response to clopidogrel,and the mean PLADP of the CLRwas(47,69 ±7.77)%;while as 410 patients(83.7%)were clopidogrel normal responser(CNR),and the mean PLADPOf the responders was(23.40 ±8.9)%.Univariate analysis showed a significant difference in the concentration of CAMD in plasmabetween the clopidogrel resistance and non-resistance group(P=0.007).As the same,left ventricular end-diastolic diameter(LVEDD),left ventricular ejection fraction(LVEF),smoking,previous history of PCI and concentration of CAMD were significant predictors of ischemic events(P<0.05).Logistic regression analysis revealed that LVEF(OR:8.50;95%CI:1.62-44.50;P=0.01)and previous history of PCI(OR:0.92;95%CI:0.84-1.00;P=0.04)were the independent risk factors for MACE.Conclusion:CLRismuch common in Chinese patients with CAD.Concentration of CAMD in plasma is the independent risk factor for CLR.Patients with lower LVEF and with previous history of PCI will suffer higher risk of MACE.