脑卒中患者服用醋硝香豆素后的抗凝稳定性:药物基因组学和后天因素的作用

IF 1.9 4区 医学 Q3 CLINICAL NEUROLOGY
Annals of Indian Academy of Neurology Pub Date : 2024-05-01 Epub Date: 2024-06-22 DOI:10.4103/aian.aian_886_23
Ashish Kant Dubey, Jayantee Kalita, Mohammad Firoz Nizami, Surendra Kumar, Usha Kant Misra
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引用次数: 0

摘要

目的:药物基因组学在药物代谢中发挥着重要作用。稳定的抗凝对于心脑血管中风和脑静脉窦血栓形成(CVST)的一级和二级预防非常重要。我们报告了细胞色素 P450(CYP2C9*2/*3)和维生素 K 环氧化物还原酶亚基 1(VKORC1)基因型和获得性原因在心脑血管栓塞性中风和 CVST 患者服用醋硝香豆素后维持抗凝稳定性的作用:研究对象包括 157 名服用醋硝香豆素的心肌栓塞性中风和 CVST 患者。注意他们的合并症、用药和饮食习惯。随访期间测量了凝血酶原时间和国际标准化比值(INR),并将凝血状态分为稳定型(>50%的场合在治疗范围内)和不稳定型(>50%的场合低于或高于治疗范围)。通过聚合酶链式反应-限制性片段长度多态性对 VKORC1、CYP2C9*2 和 CYP2C9*3 进行了基因分型。注意出血和栓塞并发症。采用多变量分析评估了 INR 不稳定的预测因素:47.8%的患者 INR 稳定,52.2%的患者 INR 不稳定。突变基因型患者需要低剂量的醋硝香豆素。预测 INR 不稳定的因素有:金属瓣膜(几率比 [OR] 4.07,95% 置信区间 [CI]1.23-13.49,P = 0.02)、使用地高辛(OR 0.031,95% CI 0.13-0.74,P = 0.09)、质子泵抑制剂(OR 0.031,95% CI 0.13-0.74,P = 0.09)。09)、质子泵抑制剂(OR 0.23,95% CI 0.06-0.91,P = 0.037)、丙戊酸钠(OR 0.22,95% CI 0.05-0.85,P = 0.029)和 CYP2C9*2 基因型(OR 5.57,95% CI 1.19-26.06,P = 0.02):VKORC1、CYP2C9*2和CYP2C9*3的变异基因型需要较低剂量的醋硝香豆素,而CYP2C9*2与不稳定的INR相关。用药是一个需要关注的可改变的风险因素。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Stability of Anticoagulation Following Acenocoumarin in Stroke Patients: Role of Pharmacogenomics and Acquired Factors.

Objective: Pharmacogenomics plays an important role in drug metabolism. A stable anticoagulation is important for primary and secondary prevention of cardioembolic stroke and cerebral venous sinus thrombosis (CVST). We report the role of cytochrome P450 ( CYP2C9*2/*3 ) and vitamin K epoxide reductase subunit 1 ( VKORC1 ) genotypes and acquired causes in maintaining stability of anticoagulation following acenocoumarin in cardioembolic stroke and CVST.

Methods: The study comprised 157 individuals with cardioembolic stroke and CVST who were on acenocoumarin. Their comorbidities, comedication, and dietary habits were noted. Prothrombin time and international normalized ratio (INR) were measured during follow-up, and the coagulation status was categorized as stable (>50% occasions in therapeutic range) and unstable (>50% below and above therapeutic range). Genotyping of VKORC1 , CYP2C9*2 , and CYP2C9*3 was done by polymerase chain reaction-restriction fragment length polymorphism. Bleeding and embolic complications were noted. The predictors of unstable INR were evaluated using multivariate analysis.

Results: INR was stable in 47.8% and unstable in 52.2% of patients. Patients with mutant genotypes required low dose of acenocoumarin. The predictors of unstable INR were metallic valve (odds ratio [OR] 4.07, 95% confidence interval [CI] 1.23-13.49, P = 0.02), use of digoxin (OR 0.031, 95% CI 0.13-0.74, P = 0.09), proton pump inhibitor (OR 0.23, 95% CI 0.06-0.91, P = 0.037), sodium valproate (OR 0.22, 95% CI 0.05-0.85, P = 0.029), and CYP2C9*2 genotype (OR 5.57, 95% CI 1.19-26.06, P = 0.02).

Conclusions: Variant genotypes of VKORC1 , CYP2C9*2 , and CYP2C9*3 required lower dose of acenocoumarin, and CYP2C9*2 was associated with unstable INR. Comedication is a modifiable risk factor that needs attention.

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来源期刊
Annals of Indian Academy of Neurology
Annals of Indian Academy of Neurology Nervous System Diseases-
CiteScore
2.20
自引率
11.80%
发文量
293
审稿时长
29 weeks
期刊介绍: The journal has a clinical foundation and has been utilized most by clinical neurologists for improving the practice of neurology. While the focus is on neurology in India, the journal publishes manuscripts of high value from all parts of the world. Journal publishes reviews of various types, original articles, short communications, interesting images and case reports. The journal respects the scientific submission of its authors and believes in following an expeditious double-blind peer review process and endeavors to complete the review process within scheduled time frame. A significant effort from the author and the journal perhaps enables to strike an equilibrium to meet the professional expectations of the peers in the world of scientific publication. AIAN believes in safeguarding the privacy rights of human subjects. In order to comply with it, the journal instructs all authors when uploading the manuscript to also add the ethical clearance (human/animals)/ informed consent of subject in the manuscript. This applies to the study/case report that involves animal/human subjects/human specimens e.g. extracted tooth part/soft tissue for biopsy/in vitro analysis.
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