Nghiên cứu ứng dụng tính đa hình gen đột biến kháng clopidogrel trong điều trị sau đặt stent động mạch vành

Impact of CYP2C19 Polymorphism on Platelet Response to Clopidogrel in Vietnamese Patients with Percutaneous Coronary Intervention Nguyễn Đoàn Thủy Bùi Đình Tùng, Nguyễn Thị Ngọc Hồng Hanoi Medical University BACKGROUND • Clopidogrel is one of the most widely used P2Y12 inhibitors in conjunction with aspirin for patients with PCI to prevent stent thrombosis • There is significant interindividual variability in clopidogrel responsiveness Metabolism of Clopidogrel Polymorphisms of CYP genes and other genes affecting metabolism of Clopidogrel BACKGROUND Carriers of loss-of-function (LoF) CYP2C19 alleles are at higher risk of stent thrombosis and other cardiovascular events OBJECTIVE Evaluate the influence of CYP2C19 polymorphisms on platelet response to clopidogrel in patients with PCI STUDY SUBJECTS • Outpatients undergoing PCI in Vietnam National Heart Institute, Bach Mai Hospital • Had received clopidogrel (75mg/d) and aspirin (81 mg/d) for at least month prior to the study Patient selection (n=30) Complete blood count testing Platelet funtion testing (1st time) CYP2C19 genotyping Extensive metabolizers Noncarriers (n=10) Intermediate metabolizers Carriers of LoF allele (n=19) Poor metabolizers Carriers of LoF alleles (n=1) Continue with current clopidogrel dose (75mg/d) Higher dose of clopidogrel (225mg/d) in 30 days Ticagrelor (90mg bid) in 30 days Platelet function testing (2nd time) Platelet function testing (2nd time) STATISTICAL ANALYSIS Performed using Stata11 software Demographic data CYP2C19 genotype and allele frequency Genotype n % *1/*1 10 33.3 *1/*2 18 60.0 *1/*3 3.3 *2/*2 3.3 Allele n % *1 39 65.0 *2 20 33.3 *3 1.7 Association between Status as a Carrier of a CYP2C19 LoF Allele and the Primary Efficacy Outcome (death from cardiovascular causes, myocardial infarction, or stroke) in 1459 subjects in TRITON-TIMI 38 study Mega et al., New England Journal of Medicine 2009 Association between Status as a Carrier of a CYP2C19 LoF Allele and Stent Thrombosis in 1459 subjects in TRITON-TIMI 38 study Mega et al., New England Journal of Medicine 2009 Comparison of platelet aggregation (%) between IM, before increasing dose of Clopidogrel and EM Agonists IM (1st time) EM P ADP 33.5 ± 8.7 19.2 ± 13.6 0.03 Ristocetin 58.75 ± 21.27 51.5 ± 28.19 0.21 Comparison of platelet aggregation (%) in IM before and 30 days after increasing dose of Clopidogrel Agonists IM (1st time) IM (2nd time) P ADP 33.5 ± 8.7 19.5 ± 5.9 0.01 Ristocetin 58.75 ± 21.27 60.25 ± 38.03 0.53 Comparison of platelet aggregation (%) between IM, 30 days after increasing dose of Clopidogrel and EM Agonists IM (2nd time) EM P ADP 19.5 ± 5.9 19.2 ± 13.6 0.81 Ristocetin 60.25 ± 38.03 51.5 ± 28.19 0.54 Platelet aggregation (%) in PM, before and 30 days after taking Ticagrelor Agonists PM (1st time) PM (2nd time) ADP 52 Ristocetin 13 27 CONCLUSION • CYP2C19 genotype might be a significant contributor to the variability in the platelet response to clopidogrel therapy in Vietnamese patients with PCI TAKE-HOME MESSAGE • Application of CYP2C19 genotype to treatment: – Clopidogrel 75mg/d for Extensive metabolizers – Higher dose of Clopidogrel (225mg/d) for Intermediate metabolizers – Newer drugs, such as Ticagrelor (90mg bid) for Poor metabolizers THANKS FOR YOUR ATTENTION! ... significant interindividual variability in clopidogrel responsiveness Metabolism of Clopidogrel Polymorphisms of CYP genes and other genes affecting metabolism of Clopidogrel BACKGROUND Carriers of... CYP2C19 genotype might be a significant contributor to the variability in the platelet response to clopidogrel therapy in Vietnamese patients with PCI TAKE-HOME MESSAGE • Application of CYP2C19 genotype... alleles are at higher risk of stent thrombosis and other cardiovascular events OBJECTIVE Evaluate the influence of CYP2C19 polymorphisms on platelet response to clopidogrel in patients with PCI