Antiplatelet Efficacy Of P2Y12 Receptor Antagonists In Patients With Different CYP2C19 Genotypes

Objective: Combining CYP2C19 gene polymorphism,we compared the antiplatelet efficacy of clopidogrel and ticagrelor in patients with acute coronary syndrome(ACS)after percutaneous coronary intervention(PCI).Methods: 7039 patients with acute coronary syndrome who underwent PCI in the Department of Cardiology,First Affiliated Hospital of China Medical University from April 2014 to December 2016 were selected.The incidence of acute/sub-acute thrombosis in stents in PCI patients was analyzed,and the proportion of CYP2C19 gene fast-metabolic and non-fast-metabolic types in patients with acute/sub-acute thrombosis in stents was calculated.Then 2378 patients who completed the CYP2C19 gene polymorphism were screened out from all patients undergoing PCI,and the proportion of CYP2C19 gene metabolites was calculated.Finally,regular administration of baiaspirin(100 mg daily maintenance dose after 300 mg loading dose)and a P2Y12 receptor antagonist(75 mg daily maintenance dose after 300 mg loading dose of clopidogrel and 90 mg twice daily maintenance dose after 180 mg loading dose of ticagrelor)were screened out from all patients with perfect CYP2C19 genotype.The platelet aggregation rate was measured by light turbidimetry(ADP induction)after 3 days of maintenance dose.A total of 1748 patients were divided into clopidogrel group and ticagrelor group according to the application of P2Y12 receptor antagonists.The platelet aggregation rate and major adverse Cardiovascular events during hospitalization were compared between clopidogrel group and ticagrelor group.The incidence of ascular events(MACE),acute/sub-acute thrombosis in stents and hemorrhagic events were compared between clopidogrel group and ticagrelor group in different CYP2C19 genotypes.Results: 1.The percentage of CYP2C19 gene extensive metabolizer,intermediate metabolizer and poor metabolizer in patients with PCI was 43.43%,44.83% and 12.74%,respectively.2.Compared with clopidogrel group,the platelet aggregation rate was lower in ticagrelor group during hospitalization(43.92±15.95 VS 37.46±0.08;P<0.05);and there was no significant difference in MACE events,acute/sub-acute thrombosis in stents and total bleeding events between the two groups during hospitalization(P > 0.05),but the incidence of minor bleeding events was higher in Ticagrelor group(0.72% VS 2.25%;P<0.05).3.For patients taking clopidogrel,the platelet aggregation rate of fast metabolic type was lower than that of non-fast metabolic type(40.32±17.04 VS 46.63±14.50;P<0.05),and there was no significant difference between the platelet aggregation rate of fast metabolic type and that of non-fast metabolic type in patients taking ticagrelor(37.10±0.07 VS 38.13±0.09;P>0.05).4.From April 2014 to December 2016,22 patients with acute/sub-acute thrombosis in stent were treated with clopidogrel.The incidence of acute/sub-acute thrombosis in stent was 0.31% in PCI patients.The incidence of acute/sub-acute thrombosis in stent was 0.35%,0.33% and 0.26% in 2014,2015 and 2016,respectively.5.The proportion of fast and non-fast metabolites of CYP2C19 gene in patients with acute/sub-acute stent thrombosis was 22.73% and 72.27% respectively..Conclusion: 1.The incidence of stent thrombosis in patients with PCI is decreasing year by year.All patients with acute/subacute stent thrombosis are oral clopidogrel patients,and the proportion of non-fast metabolic type is significantly higher than that of fast metabolic type.2.In PCI patients with CYP2C19 gene detection,The percentage of CYP2C19 gene extensive,intermediate and poor metabolizer in patients with PCI was 43.43%,44.83% and 12.74%,respectively.3.The platelet aggregation rate of ticagrelor group was lower than that of clopidogrel group,and did not increase the risk of total bleeding.