氯吡格雷和阿司匹林联合治疗可预防携带CYP2C19*2功能降低等位基因的缺血性中风患者早期神经功能恶化。
Dual therapy with clopidogrel and aspirin prevents early neurological deterioration in ischemic stroke patients carrying CYP2C19*2 reduced-function alleles.
作者信息
Lin Jing, Han Zhao, Wang Chun, Yi Xingyang, Chai Zhenxiao, Zhou Qiang, Huang Ruyue
机构信息
Department of Neurology, Third Affiliated Hospital of Wenzhou Medical University, Ruian, 325200, Zhejiang, China.
Department of Neurology, Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, Zhejiang, China.
出版信息
Eur J Clin Pharmacol. 2018 Sep;74(9):1131-1140. doi: 10.1007/s00228-018-2468-7. Epub 2018 May 26.
PURPOSE
To investigate the associations between CYP2C19 genotypes and early neurological deterioration (END), and to carry out a stratified analysis of the effectiveness of clopidogrel alone and dual antiplatelet therapy with clopidogrel and aspirin for prevention of END according to CYP2C19 genotypes in ischemic stroke (IS) patients.
METHODS
This was a prospective, observational, two-center study. A total of 375 acute IS patients were enrolled. Platelet aggregation was measured before and after the 7- to 10-day treatment. Clopidogrel resistance (CR) was assessed by adenosine diphosphate-induced platelet aggregation. CYP2C192 (rs4244285) and CYP2C193 (rs4986893) genotypes were examined using mass spectrometry. The primary outcome was END during the 10 days after admission.
RESULTS
Among the 375 patients, 144 patients received clopidogrel alone, 231 patients took clopidogrel plus aspirin, 153 patients (40.8%) had CR, 95 patients (25.3%) experienced END. Patients carrying CYP2C192 AG/AA (CYP2C192 reduced-function alleles) and CR were associated with a higher risk for END, and dual antiplatelet therapy was associated with a lower risk for END. Stratified analyses revealed that there was no significant difference in the incidence of END between patients not carryingCYP2C192 reduced-function alleles who received clopidogrel plus aspirin and those who received clopidogrel alone. However, dual antiplatelet therapy was more effective at reducing END and inhibiting platelet aggregation than clopidogrel alone for carriers of at least one CYP2C192 reduced-function allele.
CONCLUSIONS
The frequency of END was very high after acute IS in the Chinese population. Dual therapy with clopidogrel and aspirin may be adequate for patients carrying CYP2C19*2 reduced-function alleles. Genetic testing may be useful to guide personalized and precise antiplatelet therapy.
CLINICAL TRIAL REGISTRATION INFORMATION
The study described here is registered at http://www.chictr.org / (unique Identifier: ChiCTR-OCH-14004724).
目的
探讨CYP2C19基因多态性与早期神经功能恶化（END）之间的关系，并根据缺血性卒中（IS）患者的CYP2C19基因多态性，对氯吡格雷单药治疗及氯吡格雷联合阿司匹林双重抗血小板治疗预防END的有效性进行分层分析。
方法
这是一项前瞻性、观察性、双中心研究。共纳入375例急性IS患者。在7至10天治疗前后测量血小板聚集情况。通过二磷酸腺苷诱导的血小板聚集评估氯吡格雷抵抗（CR）。采用质谱法检测CYP2C192（rs4244285）和CYP2C193（rs4986893）基因多态性。主要结局为入院后10天内的END。
结果
375例患者中，144例患者接受氯吡格雷单药治疗，231例患者接受氯吡格雷联合阿司匹林治疗，153例患者（40.8%）存在CR，95例患者（25.3%）发生END。携带CYP2C192 AG/AA（CYP2C192功能降低等位基因）和CR的患者发生END的风险较高，双重抗血小板治疗与较低的END风险相关。分层分析显示，未携带CYP2C192功能降低等位基因的患者接受氯吡格雷联合阿司匹林治疗与接受氯吡格雷单药治疗的END发生率无显著差异。然而，对于至少携带一个CYP2C192功能降低等位基因的携带者，双重抗血小板治疗在降低END和抑制血小板聚集方面比氯吡格雷单药治疗更有效。
结论
中国人群急性IS后END的发生率很高。氯吡格雷和阿司匹林联合治疗可能适用于携带CYP2C19*2功能降低等位基因的患者。基因检测可能有助于指导个性化和精准的抗血小板治疗。
临床试验注册信息
本文所述研究已在http://www.chictr.org /注册（唯一标识符：ChiCTR-OCH-14004724）。
Zotero 插件