Background The CYP2C19 G681A single polymorphism has been proven to affect clopidogrel responsiveness. However, the effect of coexisting polymorphisms of other genes has not yet been reported in the Chinese population...Background The CYP2C19 G681A single polymorphism has been proven to affect clopidogrel responsiveness. However, the effect of coexisting polymorphisms of other genes has not yet been reported in the Chinese population. This study investigated the effect of coexisting polymorphisms of CYP2C19 and P2Y12 on clopidogrel responsiveness and adverse clinical events in Chinese patients. Methods In 577 Han Chinese patients undergoing stent placement because of acute coronary syndrome had platelet reactivity assessed by thromboelastography, and the CYP2C19 G681A and P2Y12 C34T polymorphisms were detected by the ligase detection reaction. Primary clinical endpoints included cardiovascular death, nonfatal myocardial infarction, target vessel revascularization, and stent thrombosis. The secondary clinical endpoints were thrombolysis in myocardial infarction bleeding. The follow-up period was 12 months. Results Genotyping revealed 194 carriers of the wild type GG genotype of CYP2C19 and the wild type CC genotype of P2Y12 （group 1）, 102 carriers of the wild type GG genotype of CYP2C19 and the mutational T allele of P2Y12 （group 2）, 163 carriers of the mutational A allele of CYP2C19 and the wild type CC genotype of P2Y12 （group 3）, and 118 carriers of the mutational A allele of CYP2C19 and the mutational T allele of P2Y12 （group 4）. Group 4 had the lowest ADP-inhibition （49.74＋32.61） and the highest prevalence of clopidogrel low response （29.7%） of the four groups. The rate of the composite of primary clinical endpoints increased more in group 4 （8.5%） than in the other three groups; the rate of composite primary endpoints in group 2 （2.9%） and group 3 （3.7%） were not significantly different than that of group 1 （1.5%）. Conclusion Coexisting polymorphisms of different genes affected clopidogrel responsiveness and clinical outcome more than single polymorphism in Chinese patients with acute coronary syndrome undergoing percutaneous coronary intervention.展开更多
Platelet inhibition with aspirin is the cornerstone of medical therapy for coronary artery disease.In the era of percutaneous coronary intervention with drug-eluting stents,dual anti-platelet therapy with the addition...Platelet inhibition with aspirin is the cornerstone of medical therapy for coronary artery disease.In the era of percutaneous coronary intervention with drug-eluting stents,dual anti-platelet therapy with the addition of clopidogrel(Plavix,Bristol-Myers Squibb,New York,NY)became the mainstay of therapy.However,with the advent of newer oral antiplatelet medications,including prasugrel(Effient?,Eli Lilly,Indianapolis,Indiana)and ticagrelor(Brilinta?,Astra-Zeneca,Cambridge,United Kingdom),choosing the appropriate platelet inhibitor has become more nuanced.The optimal regimen differs based on patient characteristics,clinical situation,and the condition being treated,with differing risk and safety profiles for these medications.This review explores the appropriate use of antiplatelet therapy for stable ischemic heart disease,acute coronary syndrome,stroke,and peripheral vascular disease.Furthermore,we evaluate the data behind the use of antiplatelet therapy in patients on oral anticoagulation.By understanding the biochemistry of platelet aggregation,the pharmacology of platelet inhibitors,and the extensive clinical trial data that informs current guideline recommendations we aim to better understand the role of clopidogrel in patients with cardiovascular disease.展开更多
文摘Background The CYP2C19 G681A single polymorphism has been proven to affect clopidogrel responsiveness. However, the effect of coexisting polymorphisms of other genes has not yet been reported in the Chinese population. This study investigated the effect of coexisting polymorphisms of CYP2C19 and P2Y12 on clopidogrel responsiveness and adverse clinical events in Chinese patients. Methods In 577 Han Chinese patients undergoing stent placement because of acute coronary syndrome had platelet reactivity assessed by thromboelastography, and the CYP2C19 G681A and P2Y12 C34T polymorphisms were detected by the ligase detection reaction. Primary clinical endpoints included cardiovascular death, nonfatal myocardial infarction, target vessel revascularization, and stent thrombosis. The secondary clinical endpoints were thrombolysis in myocardial infarction bleeding. The follow-up period was 12 months. Results Genotyping revealed 194 carriers of the wild type GG genotype of CYP2C19 and the wild type CC genotype of P2Y12 （group 1）, 102 carriers of the wild type GG genotype of CYP2C19 and the mutational T allele of P2Y12 （group 2）, 163 carriers of the mutational A allele of CYP2C19 and the wild type CC genotype of P2Y12 （group 3）, and 118 carriers of the mutational A allele of CYP2C19 and the mutational T allele of P2Y12 （group 4）. Group 4 had the lowest ADP-inhibition （49.74＋32.61） and the highest prevalence of clopidogrel low response （29.7%） of the four groups. The rate of the composite of primary clinical endpoints increased more in group 4 （8.5%） than in the other three groups; the rate of composite primary endpoints in group 2 （2.9%） and group 3 （3.7%） were not significantly different than that of group 1 （1.5%）. Conclusion Coexisting polymorphisms of different genes affected clopidogrel responsiveness and clinical outcome more than single polymorphism in Chinese patients with acute coronary syndrome undergoing percutaneous coronary intervention.
文摘Platelet inhibition with aspirin is the cornerstone of medical therapy for coronary artery disease.In the era of percutaneous coronary intervention with drug-eluting stents,dual anti-platelet therapy with the addition of clopidogrel(Plavix,Bristol-Myers Squibb,New York,NY)became the mainstay of therapy.However,with the advent of newer oral antiplatelet medications,including prasugrel(Effient?,Eli Lilly,Indianapolis,Indiana)and ticagrelor(Brilinta?,Astra-Zeneca,Cambridge,United Kingdom),choosing the appropriate platelet inhibitor has become more nuanced.The optimal regimen differs based on patient characteristics,clinical situation,and the condition being treated,with differing risk and safety profiles for these medications.This review explores the appropriate use of antiplatelet therapy for stable ischemic heart disease,acute coronary syndrome,stroke,and peripheral vascular disease.Furthermore,we evaluate the data behind the use of antiplatelet therapy in patients on oral anticoagulation.By understanding the biochemistry of platelet aggregation,the pharmacology of platelet inhibitors,and the extensive clinical trial data that informs current guideline recommendations we aim to better understand the role of clopidogrel in patients with cardiovascular disease.
