| 摘要: |
| ［摘要］ 目的 观察基于氯吡格雷相关基因多态性和血小板聚集检测结果指导缺血性脑卒中患者个体化治疗的应用效果。方法 招募2022年1月至2024年1月梧州市工人医院神经内科收治的缺血性脑卒中患者120例，采用随机数字表法将其分为研究组和对照组，各60例。对照组予常规抗血小板治疗（口服氯吡格雷75 mg/次，1次/d；阿司匹林100 mg/次，1次/d）。研究组常规口服阿司匹林（100 mg/次，1次/d），并根据氯吡格雷相关基因［包括CYP2C19*2（rs4244285）、CYP2C19*3（rs4986893）、CYP2C19*17（rs12248560）、ABCB1 C3435T（rs1045642）和CES1 G143E（rs71647871）］检测结果以及血小板聚集检测结果制订个体化用药方案。CYP2C19基因表型为超快代谢（UM）型和快速代谢（EM）型，ABCB1 C3435T携带G等位基因的患者，使用氯吡格雷治疗。CYP2C19基因表型为中间代谢（IM）型和慢速代谢（PM）型，ABCB1 C3435T携带A等位基因的患者，使用替格瑞洛治疗。CYP2C19基因表型为EM型，ABCB1 C3435T为AA型的患者，以及CYP2C19基因表型为IM型，ABCB1 C3435T为GG型的患者，初步使用氯吡格雷治疗。用药5 d后，若血小板二磷酸腺苷（ADP）受体聚集率<30%则继续使用氯吡格雷治疗，若血小板ADP受体聚集率≥30%则更换为替格瑞洛治疗。若患者CES1 G143E为CT型或TT型，则使用替格瑞洛治疗。随访1年，比较两组发生主要不良心脑血管事件（MACCE）的情况，并分析不同基因型对氯吡格雷个体化治疗预后的影响。结果 基于氯吡格雷相关基因多态性和血小板聚集检测结果，研究组共有28例调整用药。1年随访中两组均无失访病例，对照组发生MACCE 21例，研究组发生MACCE 7例，研究组无MACCE情况更优［HR（95%CI）=3.37（1.55～7.31），P=0.002］。在研究组患者中，CYP2C19基因表型为UM型/EM型者的MACCE发生情况与IM型/PM型者比较差异无统计学意义［HR（95%CI）=1.92（0.42～8.85），P=0.400］，ABCB1 C3435T基因型为GG型者发生MACCE情况与GA型/AA型者比较差异无统计学意义［HR（95%CI）=0.34（0.07～1.57），P=0.165］。结论 基于氯吡格雷相关基因多态性和血小板聚集检测结果指导缺血性脑卒中患者个体化治疗，可降低MACCE的发生风险。 |
| 关键词: 氯吡格雷 替格瑞洛 缺血性脑卒中 血小板聚集 个体化治疗 主要不良心脑血管事件 |
| DOI：10.3969/j.issn.1674-3806.2025.12.14 |
| 分类号:R 743.3 |
| 基金项目:梧州市科技计划项目（编号：202102181）；梧州市卫生健康委员会科研课题（编号：WZWS-G2022005） |
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| Observation on application effect of individualized treatments for ischemic stroke patients guided by the results of clopidogrel-related gene polymorphism and platelet aggregation tests |
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LI Zhaoquan1, HUANG Jinshi1, LI Tao1, CHEN Yingdao2, CHEN Xiaoling2, WU Lifang1
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1.Department of Clinical Pharmacy, Wuzhou Gongren Hospital, Wuzhou 543001, China; 2.Department of Neurology, Wuzhou Gongren Hospital, Wuzhou 543001, China
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| Abstract: |
| ［Abstract］ Objective To observe the application effect of individualized treatments for ischemic stroke patients guided by the results of clopidogrel-related gene polymorphism and platelet aggregation tests. Methods A total of 120 patients with ischemic stroke who were admitted to Department of Neurology, Wuzhou Gongren Hospital from January 2022 to January 2024 were recruited and divided into research group and control group by random number table method, with 60 patients in each group. The control group was given conventional antiplatelet therapy［oral administration of clopidogrel(75 mg q.d.) and aspirin(100 mg q.d.)］. The research group was given conventional oral administration of aspirin(100 mg q.d.), and individualized treatment regimens were formulated according to the results of clopidogrel-related genes［including CYP2C19*2(rs4244285)、CYP2C19*3(rs4986893)、CYP2C19*17(rs12248560), ABCB1 C3435T(rs1045642) and CES1 G143E(rs71647871)］ test and platelet aggregation test. The patients with CYP2C19 gene phenotypes of ultrarapid metabolizer(UM) and extensive metabolizer(EM) and ABCB1 C3435T carrying the G allele were treated with clopidogrel. The patients with CYP2C19 gene phenotypes of intermediate metabolizer(IM) and poor metabolizer(PM) and ABCB1 C3435T carrying the A allele were treated with ticagrelor. The patients with CYP2C19 gene phenotype of EM and ABCB1 C3435T of AA type, as well as those with CYP2C19 gene phenotype of IM and ABCB1 C3435T of GG type, were initially treated with clopidogrel. After 5 days of the medication, if the platelet adenosine diphosphate(ADP) receptor aggregation rate was less than 30%, clopidogrel treatment should be continued, and if the platelet ADP receptor aggregation rate was greater than or equal to 30%, clopidogrel treatment should be switched to ticagrelor treatment. If the patients′ CES1 G143E was CT type or TT type, ticagrelor was used for the treatment. The patients were followed up for 1 year to compare the occurrence of major adverse cardiovascular and cerebrovascular events(MACCE) between the two groups, and to analyze the impact of different genotypes on the prognosis of the patients receiving individualized treatment of clopidogrel. Results According to the results of clopidogrel-related gene polymorphism and platelet aggregation tests, a total of 28 patients in the research group had their medications adjusted. During the 1-year follow-up, no patients were lost to follow-up in either group. There were 21 cases of MACCE in the control group and 7 cases of MACCE in the research group. The research group had better results in terms of MACCE-free situation［HR(95%CI)=3.37(1.55-7.31), P=0.002］. In the patients of the research group, there was no statistically significant difference in the occurrence of MACCE between the patients with CYP2C19 gene phenotypes of UM type/EM type and those with CYP2C19 gene phenotypes of IM type/PM type［HR(95%CI)=1.92(0.42-8.85), P=0.400］, and there was no statistically significant difference in the occurrence of MACCE between the patients with ABCB1 C3435T gene of GG type and those with ABCB1 C3435T gene of GA type/AA type［HR(95%CI)=0.34(0.07-1.57), P=0.165］. Conclusion Individualized treatments guided by the results of clopidogrel-related gene polymorphism and platelet aggregation tests can reduce the risk of MACCE in ischemic stroke patients. |
| Key words: Clopidogrel Ticagrelor Ischemic stroke Platelet aggregation Individualized treatment Major adverse cardiovascular and cerebrovascular events(MACCE) |
