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首页> 外文期刊>Journal of stroke and cerebrovascular diseases: The official journal of National Stroke Association >CYP2C19 Loss-of-Function is Associated with Increased Risk of Ischemic Stroke after Transient Ischemic Attack in Intracranial Atherosclerotic Disease
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CYP2C19 Loss-of-Function is Associated with Increased Risk of Ischemic Stroke after Transient Ischemic Attack in Intracranial Atherosclerotic Disease

机译：CYP2C19在颅内动脉粥样硬化疾病中瞬时缺血性发作后缺血性脑卒中风险增加有关

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Objectives: Intracranial atherosclerotic disease (ICAD) is responsible for 8-10% of acute ischemic strokes, and resistance to antiplatelet therapy is prevalent. CYP2C19 gene loss-of-function (up to 45% of patients) causes clopidogrel resistance. For patients with asymptomatic ICAD and ICAD characterized by transient ischemic attack (TIA), this study measures the effect of CYP2C19 loss-of-function on ischemic stroke risk during clopidogrel therapy. Materials and Methods: From a deidentified database of medical records, patients were selected with ICD-9 /10 code for ICAD, availability of CYP2C19 genotype, clopidogrel exposure, and established patient care. Dual-antiplatelet therapy patients were included. Patients with prior ischemic stroke, other neurovascular condition, intracranial angioplasty/stenting, or observation time <1 month were excluded. Time-to-event analysis using Cox regression was conducted to model first-time ischemic stroke events based on CYP2C19 lossof-function allele and adjusted for age, gender, race, length of aspirin, length of concurrent antiplatelet/ anticoagulant treatment, diabetes, coagulopathy, hypertension, heart disease, atrial fibrillation, and lipid disorder. Subset analyses were performed for asymptomatic and post-TIA subtypes of ICAD. Results: A total of 337 patients were included (median age 68, 58% male, 88% Caucasian, 26% CYP2C19 loss-offunction). A total of 161 (47.8%) patients had TIA at time of ICAD diagnosis, while 176 (52.2%) were asymptomatic. First-time ischemic stroke was observed among 20 (12.4%) post-TIA ICAD patients and 17 (9.7%) asymptomatic ICAD patients. Median observation time was 2.82 [IQR 1.13-5.17] years. CYP2C19 loss-of-function allele was associated with ischemic stroke event (HR 2.2, 95% CI 1.1-4.3, p=0.020) after adjustment. Post-TIA ICAD patients had a higher risk of ischemic stroke from CYP2C19 loss-of-function (HR 3.4, 95% CI 1.4-8.2, p=0.006). Conclusions: CYP2C19 loss-of-function was associated with 3-fold increased risk of first-time ischemic stroke for ICAD patients treated with clopidogrel after TIA. This effect was not observed for asymptomatic ICAD. CYP2C19-guided antiplatelet selection may improve stroke prevention in ICAD after TIA.
机译：目的：颅内动脉粥样硬化性疾病（ICAD）是8-10%的急性缺血性中风的病因，抗血小板治疗的耐药性普遍存在。CYP2C19基因功能丧失（高达45%的患者）导致氯吡格雷抵抗。对于无症状ICAD和以短暂性脑缺血发作（TIA）为特征的ICAD患者，本研究测量了氯吡格雷治疗期间CYP2C19功能丧失对缺血性中风风险的影响。材料和方法：从一个身份不明的病历数据库中，根据ICAD的ICD-9/10编码、CYP2C19基因型的可用性、氯吡格雷暴露和既定的患者护理选择患者。包括双重抗血小板治疗患者。排除先前患有缺血性卒中、其他神经血管疾病、颅内血管成形术/支架植入术或观察时间<1个月的患者。基于CYP2C19功能丧失等位基因，采用Cox回归进行时间-事件分析，以模拟首次缺血性中风事件，并根据年龄、性别、种族、阿司匹林服用时间、同时抗血小板/抗凝血剂治疗时间、糖尿病、凝血病、高血压、心脏病、心房颤动和脂质紊乱进行调整。对ICAD的无症状亚型和TIA后亚型进行子集分析。结果：共纳入337例患者（中位年龄68岁，58%男性，88%白种人，26%CYP2C19功能丧失）。共有161名（47.8%）患者在ICAD诊断时出现TIA，176名（52.2%）患者无症状。在20例（12.4%）TIA后ICAD患者和17例（9.7%）无症状ICAD患者中观察到首次缺血性卒中。中位观察时间为2.82[IQR 1.13-5.17]年。调整后CYP2C19功能丧失等位基因与缺血性卒中事件相关（HR 2.2，95%可信区间1.1-4.3，p=0.020）。TIA后ICAD患者因CYP2C19功能丧失而发生缺血性中风的风险较高（HR3.4，95%可信区间1.4-8.2，p=0.006）。结论：对于TIA后接受氯吡格雷治疗的ICAD患者，CYP2C19功能丧失与首次缺血性卒中风险增加3倍有关。无症状ICAD患者未观察到这种效应。CYP2C19指导的抗血小板选择可能改善TIA后ICAD的卒中预防。

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