Effect of drug metabolism related gene polymorphism on efficacy of clopidogrel in patients with acute coronary syndrome
10.3760/cma.j.cn114015-20220302-00164
- VernacularTitle:药物代谢相关基因多态性对急性冠状动脉综合征患者氯吡格雷疗效的影响
- Author:
Yang LI
1
;
Jiping HUO
;
Jian CUI
;
Kai WANG
;
Shuang REN
;
Li YANG
Author Information
1. 北京市大兴区人民医院药剂科，北京 102600
- Publication Type:Journal Article
- Keywords:
Acute coronary syndrome;
Cytochrome P-450 enzyme system;
Polymorphism, genetic;
Clopidogrel
- From:
Adverse Drug Reactions Journal
2022;24(10):522-527
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of drug metabolism related gene polymorphism on the efficacy of clopidogrel in patients with acute coronary syndrome (ACS).Methods:The medical records and follow-up records of ACS patients, who were hospitalized in the People′s Hospital of Daxing District between 2017 and 2019, received standardized treatment with aspirin (100 mg/day)+clopidogrel (75 mg/day), and underwent testing for genetic polymorphisms related to clopidogrel absorption/metabolism, were collected. The patients were divided into thrombotic event group and non-thrombotic event group according to whether they experienced thrombotic events such as myocardial infarction, stent thrombosis, and cerebral infarction within 1 year of treatment. The age, gender, smoking history and drinking habits, underlying diseases, drug combination, and alleles related to clopidogrel absorption/metabolism in patients in the 2 groups were compared. The factors affecting the clinical efficacy of clopidogrel was analyzed using logistic regression model.Results:A total of 342 patients were included in the analysis, including 274 males and 68 females, aged (58±9) years; of them, 78 (22.8%) developed thrombotic events. The differences in age, gender, smoking history, drinking history, hypertension, diabetes mellitus, hyperlipidemia, percutaneous coronary intervention history, proportion of combined with calcium channel antagonists, cytochrome P450 (CYP) 2C19*3, paraoxonase-1 Q192R, and adenosine triphosphate binding cassette transporter B1 C3435T between the thrombotic event group and the non-thrombotic event group were not statistically significant (all P>0.05), but the body mass index (BMI), the proportion of CYP2C19*2 GG type and CYP2C19*17 CT type in patients in the thrombotic event group were lower than those in the non-thrombotic event group (all P<0.05), and the proportion of patients with proton pump inhibitor and CYP2C19*17 CC type in the thrombotic event group was higher than that in the non-thrombotic event group (all P<0.05). Multivariate logistic regression analysis showed that high BMI ( OR=0.915, 95 %CI: 0.847-0.989, P=0.026), CYP2C19*2 GG type ( OR=0, 95 %CI: 0-0.008, P<0.001), and GA type ( OR=0.028, 95 %CI: 0.003-0.296, P=0.003) were independent protective factors for thrombotic events after clopidogrel treatment; CYP2C19*17 CC type ( OR=2 856.665, 95 %CI: 87.337-93 436.810, P<0.001) was an independent risk factor for thrombotic events after clopidogrel treatment. Conclusion:CYP2C19*2 and CYP2C19*17 mutations are important factors affecting the efficacy of clopidogrel and the occurrence of thrombotic events after treatment in ACS patients.
