Tirofiban for Stroke without Large or Medium-Sized Vessel Occlusion
Wenjie Zi, Jiaxing Song, Weilin Kong, et al
N Engl J Med 2023; 388:2025-2036
DOI: 10.1056/NEJMoa2214299
Abstract
BACKGROUND
The effects of the glycoprotein IIb/IIIa receptor inhibitor tirofiban in patients with acute ischemic stroke but who have no evidence of complete occlusion of large or medium-sized vessels have not been extensively studied.
背景
糖蛋白Ⅱb/Ⅲa受体抑制剂替罗非班在无大或中型血管完全闭塞证据的急性缺血性卒中患者中的作用尚未进行广泛研究。
METHODS
In a multicenter trial in China, we enrolled patients with ischemic stroke without occlusion of large or medium-sized vessels and with a National Institutes of Health Stroke Scale score of 5 or more and at least one moderately to severely weak limb. Eligible patients had any of four clinical presentations: ineligible for thrombolysis or thrombectomy and within 24 hours after the patient was last known to be well; progression of stroke symptoms 24 to 96 hours after onset; early neurologic deterioration after thrombolysis; or thrombolysis with no improvement at 4 to 24 hours. Patients were assigned to receive intravenous tirofiban (plus oral placebo) or oral aspirin (100 mg per day, plus intravenous placebo) for 2 days; all patients then received oral aspirin until day 90. The primary efficacy end point was an excellent outcome, defined as a score of 0 or 1 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days. Secondary end points included functional independence at 90 days and a quality-of-life score. The primary safety end points were death and symptomatic intracranial hemorrhage.
方法
在中国的一项多中心试验中，我们纳入了无大或中型血管闭塞、美国国立卫生研究院卒中量表（National Institutes of Health stroke Scale）评分≥5分并且至少1个肢体中度至重度无力的缺血性卒中患者。符合纳入条件的患者有以下四种临床表现之一：不适合接受溶栓或取栓术，并且在患者最后一次已知健康状况良好后24小时内；发病后24~96小时卒中症状进展；溶栓后早期神经功能恶化；或溶栓后4~24小时无改善。患者被分配接受为期2天的替罗非班静脉给药（+口服安慰剂）或口服阿司匹林（每日100 mg）（+安慰剂静脉给药）；所有患者随后均口服阿司匹林直至第90日。主要疗效终点是优良的结局，定义为第90日时改良Rankin量表评分（范围，0[无症状]~6[死亡]）为0或1分。次要终点包括第90日时的功能独立和生活质量评分。主要安全性终点是死亡和有症状的颅内出血。
RESULTS
A total of 606 patients were assigned to the tirofiban group and 571 to the aspirin group. Most patients had small infarctions that were presumed to be atherosclerotic. The percentage of patients with a score of 0 or 1 on the modified Rankin scale at 90 days was 29.1% with tirofiban and 22.2% with aspirin (adjusted risk ratio, 1.26; 95% confidence interval, 1.04 to 1.53, P=0.02). Results for secondary end points were generally not consistent with the results of the primary analysis. Mortality was similar in the two groups. The incidence of symptomatic intracranial hemorrhage was 1.0% in the tirofiban group and 0% in the aspirin group.
结果
共计606例患者被分配至替罗非班组，571例患者被分配至阿司匹林组。大多数患者有小梗死灶，推测为动脉粥样硬化所致。在替罗非班组和阿司匹林组中，第90日时改良Rankin量表评分为0分或1分的患者百分比分别为29.1%和22.2%（经校正的风险比，1.26；95%置信区间，1.04~1.53，P=0.02）。总体而言，次要终点结果与主要分析结果不一致。两组的死亡率相似。在替罗非班组和阿司匹林组中，有症状的颅内出血发生率分别为1.0%和0%。
CONCLUSIONS
In this trial involving heterogeneous groups of patients with stroke of recent onset or progression of stroke symptoms and nonoccluded large and medium-sized cerebral vessels, intravenous tirofiban was associated with a greater likelihood of an excellent outcome than low-dose aspirin. Incidences of intracranial hemorrhages were low but slightly higher with tirofiban. (Funded by the National Natural Science Foundation of China; RESCUE BT2 Chinese Clinical Trial Registry number, ChiCTR2000029502. opens in new tab.)
结论
本试验纳入了异质性的大、中型脑血管未闭塞、卒中症状近期发生或进展的患者，结果表明替罗非班静脉给药与小剂量阿司匹林相比，获得优良结局的可能性较大。颅内出血的发生率低，但替罗非班组略高。（由中国国家自然科学基金资助；RESCUE BT2在中国临床试验注册中心注册号为ChiCTR2000029502。）
