Open AccessInfluence of Genetic Polymorphisms on Clopidogrel Response and Clinical Outcomes in Patients with Acute Ischemic Stroke CYP2C19 Genotype on Clopidogrel Response
Author(s) -
Han Yan,
Lv HuiHui,
Liu Xu,
Dong Qiang,
Yang XiaoLi,
Li ShiXu,
Wu Shuai,
Jiang JianMing,
Luo Zheng,
Zhu DeSheng,
Zhang Yi,
Zheng Yi,
Guan YangTai,
Xu JianFeng
Publication year - 2015
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12426
Subject(s) - clopidogrel , medicine , cyp2c19 , p2y12 , single nucleotide polymorphism , stroke (engine) , genotyping , clinical endpoint , acute coronary syndrome , genotype , mace , cardiology , gastroenterology , myocardial infarction , percutaneous coronary intervention , clinical trial , gene , genetics , biology , mechanical engineering , cytochrome p450 , metabolism , engineering
Summary Objectives This study sought to evaluate the influence of the genetic polymorphisms on platelet reactivity and clinical outcomes in acute ischemic stroke patients taking clopidogrel. Background Little research has been published on relationships between genetic polymorphisms, platelet reactivity, and clinical outcomes in stroke patients treated with clopidogrel. Methods Patients hospitalized in Changhai Hospital with acute ischemic stroke were randomly enrolled into treatment with a 75‐mg daily maintenance dose of clopidogrel. Genotyping was detected by the Mass ARRAY iPLEX genotyping system (Sequenom Inc, San Diego, CA ), and platelet reactivity was evaluated by the VerifyNow P2Y12 test (Accumetrics Inc., San Diego, CA ). Sixteen single nucleotide polymorphisms ( SNP s) within 9 genes were selected and high on‐clopidogrel platelet reactivity ( HPR ) was defined as P2Y12 reaction units ( PRU ) value ≥230. The primary endpoint was ischemic events, including major adverse cardiac events ( MACE ), recurrence of stroke, transient ischemic attack ( TIA ), and the composite of vascular death, and the secondary endpoint was bleeding. Results Of the 345 patients recruited, 275 (79.7%) patients were followed up for 1 year and 122 (35.4%) patients were categorized as HPR . Among the SNP s selected, only the CYP 2C19*2 allele and the CYP 2C19*3 allele were statistically significantly associated with PRU ( P < 0.001 and P = 0.003, respectively). Similarly, the prevalence of HPR was associated with CYP 2C19*2 and CYP 2C19*3 ( P < 0.001 and P = 0.001, respectively). During the 1 year of follow‐up, a total of 64 (23.3%) cases of clinical events occurred, including 60 ischemic events and 4 bleeding events. There were no correlation between CYP 2C19 variant alleles and clinical outcomes ( P > 0.05), but a statistically significant relevance was found between the HPR and the ischemic events in 1 year of follow‐up ( P = 0.001). Conclusions CYP 2C19*2 and CYP 2C19*3 had a significant impact on clopidogrel response, but was not associated with ischemic events during 1 year of follow‐up in patients with acute ischemic stroke. HPR was an independent risk factor for ischemic events, and the VerifyNow P2Y12 test may be available to guide individualized antiplatelet therapies in stroke patients in China.