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基于CYP2C19基因多态性的经皮冠状动脉介入治疗随时间变化的临床结局

Clinical Outcomes After Percutaneous Coronary Intervention Over Time on the Basis of CYP2C19 Polymorphisms.

作者信息

Zhang Yang, Zhao Xiliang, Ye Yicong, Li Quan, Zeng Yong

机构信息

Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.

出版信息

J Cardiovasc Pharmacol. 2022 Feb 1;79(2):183-191. doi: 10.1097/FJC.0000000000001164.

Abstract

The aim of this study was to investigate the association between CYP2C19 gene polymorphisms and the risk of cardiovascular events in the early stage and subsequent period after percutaneous coronary intervention (PCI) among patients who received clopidogrel. Between October 2015 and January 2017, CYP2C19 genotyped patients who were treated with clopidogrel after PCI were enrolled in this study. Included patients were categorized as non-loss-of-function metabolizers, intermediate metabolizers, and poor metabolizers based on CYP2C19 genotype. The primary outcome was a composite of any-cause mortality, nonfatal myocardial infarction, nonfatal ischemic stroke, and stent thrombosis occurring during exposure to clopidogrel. The rates of clinical outcome events were compared between CYP2C19 phenotypes. Landmark analyses were processed at 90 days and 1 year post-PCI. Of 1341 patients, 161 (12.0%) had 2 copies of loss-of-function (LOF) alleles, 621(46.3%) had one LOF allele, and 559 (41.7%) had no LOF allele. At the 3-month follow-up, the primary outcome events were more frequent in carriers of 2 LOF alleles (5.6%) than in noncarriers (1.8%) [adjusted hazard ratio (HR) 2.944, 95% confidence interval, 1.184-7.321, P = 0.020). A similar finding was observed among in patients with acute coronary syndrome indications at the index PCI (adjusted HR 3.046, 95% confidence interval, 1.237-7.501, P = 0.015). These differences did not persist within the subsequent 9 months of follow-up, among either all comers or subjects with acute coronary syndrome. In conclusion, these data demonstrate a higher risk for ischemic events in patients with 2 CYP2C19 LOF alleles who are prescribed clopidogrel, seen at 3 months after PCI, that is not sustained for 12 months.

摘要

本研究旨在调查接受氯吡格雷治疗的患者中,CYP2C19基因多态性与经皮冠状动脉介入治疗(PCI)后早期及后续阶段心血管事件风险之间的关联。2015年10月至2017年1月,本研究纳入了PCI术后接受氯吡格雷治疗且已进行CYP2C19基因分型的患者。根据CYP2C19基因型,将纳入患者分为功能正常代谢型、中间代谢型和慢代谢型。主要结局是在氯吡格雷治疗期间发生的全因死亡率、非致死性心肌梗死、非致死性缺血性卒中及支架内血栓形成的复合事件。比较了CYP2C19各表型之间临床结局事件的发生率。在PCI术后90天和1年进行了标志性分析。1341例患者中,161例(12.0%)有2个功能缺失(LOF)等位基因拷贝,621例(46.3%)有1个LOF等位基因,559例(41.7%)无LOF等位基因。在3个月随访时,2个LOF等位基因携带者的主要结局事件发生率(5.6%)高于非携带者(1.8%)[调整后风险比(HR)2.944,95%置信区间为1.184 - 7.321,P = 0.020]。在首次PCI时具有急性冠状动脉综合征指征的患者中也观察到了类似结果(调整后HR 3.046,95%置信区间为1.237 - 7.501,P = 0.015)。在随后9个月的随访中,无论是所有患者还是急性冠状动脉综合征患者,这些差异均未持续存在。总之,这些数据表明,服用氯吡格雷的2个CYP2C19 LOF等位基因患者在PCI术后3个月时缺血事件风险较高,但这种情况在12个月内并未持续。

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