血糖控制对伴有基因变异的短暂性脑缺血发作或轻度卒中患者使用氯吡格雷疗效的影响
Impact of Glycemic Control on Efficacy of Clopidogrel in Transient Ischemic Attack or Minor Stroke Patients With Genetic Variants.
作者信息
Lin Yi, Wang Anxin, Li Jiejie, Lin Jinxi, Wang David, Meng Xia, Ou Lixian, Chen Weiqi, Zhao Xingquan, Liu Liping, Wang Yilong, Wang Yongjun
机构信息
From the Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China (Y.L., A.W., J. Li, J. Lin, X.M., W.C., X.Z., L.L., Yilong Wang, Yongjun Wang); Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, China (Y.L., L.O.); China National Clinical Research Center for Neurological Diseases, Beijing, China (Y.L., A.W., J. Li, J. Lin, X.M., W.C., X.Z., L.L., Yilong Wang, Yongjun Wang); Center of Stroke, Beijing Institute for Brain Disorders, China (Y.L., A.W., J. Li, J. Lin, X.M., W.C., X.Z., L.L., Yilong Wang, Yongjun Wang); Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, China (A.W., J. Li, J. Lin, X.M., W.C., X.Z., L.L., Yilong Wang, Yongjun Wang); and Illinois Neurological Institute Stroke Network, OSF Healthcare Systems, University of Illinois College of Medicine at Peoria (D.W.).
出版信息
Stroke. 2017 Apr;48(4):998-1004. doi: 10.1161/STROKEAHA.116.016463. Epub 2017 Mar 13.
BACKGROUND AND PURPOSE
Dysglycemia may influence the predictive value of loss-of-function allele for clinical efficacy of antiplatelet drug, but the role of glycated albumin (GA) remains unclear in patients with stroke on antiplatelet drugs.
METHODS
The CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) included 2933 patients who had GA levels and genotyping. Cox proportional hazards model was used to assess the interaction between loss-of-function allele (*2, *3) carrier status and the effect of antiplatelet therapy based on their GA levels.
RESULTS
There was significant interaction between carrier status and antiplatelet therapy regimen on the risk of recurrent stroke (=0.03) in patients with GA levels of ≤15.5%, but not in those with GA levels of >15.5% (=0.48). Only in noncarriers with low GA levels, dual-antiplatelet therapy reduced stroke recurrence (3.5%) compared with those on aspirin alone (14.7%; hazard ratio, 0.23; 95% confidence interval, 0.10-0.49; <0.001). Similar effects were observed when examined the combined vascular event or ischemic stroke. No significant difference in bleeding was found among groups.
CONCLUSIONS
In patients with minor stroke or high-risk transient ischemic attack, clopidogrel-aspirin when compared with aspirin alone reduced stroke recurrence only in noncarriers of loss-of-function allele and normal GA levels.
CLINICAL TRIAL REGISTRATION
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979589.
背景与目的
血糖异常可能会影响功能缺失等位基因对抗血小板药物临床疗效的预测价值，但糖化白蛋白（GA）在接受抗血小板药物治疗的卒中患者中的作用仍不明确。
方法
CHANCE试验（急性非致残性脑血管事件高危患者的氯吡格雷治疗）纳入了2933例有GA水平检测和基因分型的患者。采用Cox比例风险模型，根据GA水平评估功能缺失等位基因（*2、*3）携带者状态与抗血小板治疗效果之间的相互作用。
结果
GA水平≤15.5%的患者中，携带者状态与抗血小板治疗方案在复发性卒中风险方面存在显著交互作用（P = 0.03），而GA水平>15.5%的患者中则无显著交互作用（P = 0.48）。仅在GA水平低的非携带者中，与单独使用阿司匹林的患者相比，双联抗血小板治疗降低了卒中复发率（3.5%对14.7%；风险比，0.23；95%置信区间，0.10 - 0.49；P<0.001）。在检查联合血管事件或缺血性卒中时也观察到类似效果。各治疗组间出血情况无显著差异。
结论
在轻度卒中或高危短暂性脑缺血发作患者中，与单独使用阿司匹林相比，氯吡格雷联合阿司匹林仅在功能缺失等位基因非携带者且GA水平正常的患者中降低了卒中复发率。
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