不同氯吡格雷疗效检测指标的相关性及与心血管事件的关系  

Comparison of Different Testing Method on Clopidogrel Effect With the Predictive Value of Major Adverse Cardiovascular Event Occurrence in ACS Patients

作　　者：唐宁[1] 徐向东[1] 朱耀武[1] 孙自镛[1] 潘莹莹[1] 郭小梅[2] 秦瑾[2] 尹世玉[3] 

机构地区：[1]华中科技大学同济医学院附属同济医院检验科,湖北省武汉市430030 [2]华中科技大学同济医学院附属同济医院心血管科,湖北省武汉市430030 [3]华中科技大学同济医学院附属同济医院综合医疗科,湖北省武汉市430030

出　　处：《中国循环杂志》2015年第2期144-148,共5页Chinese Circulation Journal

摘　　要：目的：了解常用氯吡格雷疗效检测指标间的相关性和对心血管事件的预测能力，为选择合适的检测方法提供初步依据。 方法：同时使用二磷酸腺苷（ADP）诱导光学浊度法（LTA）血小板聚集试验、血栓弹力图（血小板图）试验、血管扩张刺激磷蛋白磷酸化试验（VASP）和CYP2C19基因型分析，检测接受氯吡格雷治疗的178例急性冠状动脉综合征患者的血小板功能，根据回访178例患者6个月发生主要不良心血管事件（MACE）情况，分为MACE组（n=21）和非MACE组（n=157），分析各检测结果相关性和对不良心血管事件的预测能力。 结果：以LTA血小板最大聚集率（LTA-PAmax）〉46%、血小板图ADP诱导的血小板最大振幅（MAADP）〉47 mm和VASP血小板反应指数（VASP-PRI）〉50%提示氯吡格雷抵抗的发生率分别为27.0%、24.2%和61.2%。178例患者中， CYP2C19快代谢型、中间代谢型、慢代谢型分别为81例（45.5%），72例（40.5%）和25例（14.0%），三型间VASP-PRI均有显著差异（P〈0.001）并呈基因剂量效应（慢代谢型〉中间代谢型〉快代谢型）；多变量Logistic回归分析中，LTA-PAmax〉46%和MAADP〉47 mm为6个月MACE发生的独立危险因素[比值比（OR）=5.99，95%可信区间（CI）：2.00~17.96， P=0.001及OR=4.72，95%CI：1.27~19.67，P=0.013]。 结论：中国人群中存在较高比例的CYP2C19功能丢失基因型，且与治疗后血小板高反应性相关；LTA-PAmax与MAADP是接受氯吡格雷治疗的急性冠状动脉综合征患者发生不良心血管事件更有效的预测指标。Objective： To compare different testing method on clopidogrel effect with the predictive value of major adverse cardiovascular event （MACE） occurrence in ACS patients in order to provide the proper examination in clinical practice. Methods： There were 4 tests conducted at the same period of time, ① ADP induced light transmission aggregometry （LTA）, ② thrombelastography （TEG）, ③ vasodilator-stimulated phosphor protein phosphorylation （VASP） and④CYP2C19 loss of function genotype analysis. A total of 178 ACS patients with clopidogrel treatment were retrospectively studied, the patients were divided into MACE group, n=21 and Non-MACE group, n=157 to compare the effect of different test with the predictive value for MACE occurrence at 6 months after medication. Results： The ADP-induced maximum platelet aggregation rate （LTA-PAmax） 〉 46%, ADP-induced platelet–fibrin clot strength （MAADP） 〉 47mm and VASP platelet reactivity index （VASP-PRI） 〉 50% indicating the occurrence rate for clopidogrel resistance were at 27.0%, 24.2% and 61.2% respectively. The CYP2C19 genotype analysis presenting the patients with extensive metabolizers （EMs）, intermediate metabolizers （IMs） and poor metabolizers （PMs） were at 81 （45.5%）, 72 （40.5%） and 25 （14.0%） respectively. The VASP-PRI values were different among the patients with EMs, IMs and PMs as PMs 〉 IMs 〉 Ems, P〈0.001. Multivariate analysis demonstrated that LTA-PAmax〉46%and MAADP〉47mm were the independent risk factors for MACE occurrence in ACS patients at 6 months after medication （OR： 5.99, 95% CI： 2.00- 17.96, P=0.001） and （OR： 4.72, 95% CI：1.27-19.67, P=0.013）. Conclusion： There was higher ratio of CYP2C19 loss of function genotypes, which might be related to higher platelet reactivity after medication. LTA-PAmax and MAADP were the better predictors for MACE occurrence in ACS patients after clopidogrel treatment.

关 键 词：氯吡格雷 血小板功能检测 CYP2C19基因型 

分 类 号：R54[医药卫生—心血管疾病]