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急性缺血性卒中或短暂性脑缺血发作后应用替格瑞洛联合阿司匹林与阿司匹林单药治疗的比较
Ticagrelor and Aspirin or Aspirin Alone in Acute Ischemic Stroke or TIA


S. Claiborne Johnston ... 心脑血管疾病 • 2020.07.16
相关阅读
• 替格瑞洛联合阿司匹林用于轻型卒中或短暂性脑缺血发作患者 • 抗血小板疗法预防早期复发性卒中 • 氯吡格雷和阿司匹林治疗急性缺血性卒中和高危短暂性脑缺血发作

摘要


背景

已经有试验评估了氯吡格雷联合阿司匹林预防缺血性卒中或短暂性脑缺血发作(TIA)后的卒中。之前的一项试验表明,在预防卒中或TIA后的血管事件或死亡方面,替格瑞洛未优于阿司匹林。迄今尚未充分研究替格瑞洛联合阿司匹林对卒中的预防效果。

 

方法

我们开展了一项随机、安慰剂对照的双盲试验,试验纳入发生轻度至中度急性非心源性缺血性卒中(美国国立卫生研究院卒中量表[National Institutes of Health Stroke Scale,NIHSS]评分≤5分[范围,0~42分,评分较高表示卒中较严重])或TIA,并且未接受溶栓或取栓术治疗的患者。我们在患者发病后24小时内以1∶1的比例将其随机分组,两组分别接受30日的替格瑞洛(180 mg负荷剂量,之后每日2次,每次90 mg)+阿司匹林(第1日300~325 mg,之后每日75~100 mg)治疗或者匹配安慰剂+阿司匹林治疗。主要结局是由30日内卒中或死亡构成的复合结局。次要结局包括30日内的后续首次缺血性卒中和残疾发生率。主要安全性结局为重度出血。

 

结果

共计11,016例患者被随机分组(替格瑞洛-阿司匹林组5,523例,阿司匹林组5,493例)。替格瑞洛-阿司匹林组303例患者(5.5%)和阿司匹林组362例患者(6.6%)发生了主要结局事件(风险比,0.83; 95%置信区间[CI],0.71~0.96;P=0.02)。替格瑞洛-阿司匹林组276例患者(5.0%)和阿司匹林组345例患者(6.3%)发生了缺血性卒中(风险比,0.79;95% CI,0.68~0.93;P=0.004)。两组的残疾发生率无显著差异。替格瑞洛-阿司匹林组28例患者(0.5%)和阿司匹林组7例患者(0.1%)发生了重度出血(P=0.001)。

 

结论

在未接受静脉内或血管内溶栓治疗的轻度至中度急性非心源性缺血性卒中(NIHSS评分≤5分)或TIA患者中,替格瑞洛联合阿司匹林用药后的复合结局(30日内卒中或死亡)风险低于阿司匹林单独用药,两组的残疾发生率无显著差异。替格瑞洛用药后的重度出血发生率较高(由阿斯利康资助,THALES在ClinicalTrials.gov注册号为NCT03354429)。





作者信息

S. Claiborne Johnston, M.D., Ph.D., Pierre Amarenco, M.D., Hans Denison, M.D., Ph.D., Scott R. Evans, Ph.D., Anders Himmelmann, M.D., Ph.D., Stefan James, M.D., Ph.D., Mikael Knutsson, Ph.D., Per Ladenvall, M.D., Ph.D., Carlos A. Molina, M.D., Ph.D., and Yongjun Wang, M.D., for the THALES Investigators*
From the Dean’s Office, Dell Medical School, University of Texas at Austin, Austin (S.C.J.); the Department of Neurology and Stroke Center, Bichat–Claude Bernard Hospital, University of Paris, Paris (P.A.); Biopharmaceuticals Research and Development, AstraZeneca, Gothenburg (H.D., A.H., M.K., P.L.), and the Department of Medical Sciences, Uppsala University, Uppsala (S.J.) — both in Sweden; the Biostatistics Center, George Washington University, Washington, DC (S.R.E.); the Stroke Unit, Vall d’Hebron Hospital, Barcelona (C.A.M.); and the Department of Neurology, Tiantan Hospital, Capital Medical University, Beijing (Y.W.). Address reprint requests to Dr. Johnston at the Dean’s Office, Dell Medical School, University of Texas at Austin, 1501 Red River St., Austin, TX 78712, or at clay.johnston@utexas.edu. *A full list of the THALES Investigators is provided in the Supplementary Appendix, available at NEJM.org.

 

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