Tao Chunrong, Liu Tianlong, Cui Tao, Liu Jie, Li Zongliang, Ren Youquan, Zhao Xingli, Xie Fuyou, Li Jianqiao, Wang Hao, Huang Ling, Li Jianjun, Wen Jianshang, Zeng Jianzhong, Zhu Junyong, Li Zhide, Li Dajun, Hu Xuefeng, Huang Biao, Wang Jing, Zhang Chi, Ye Bin, Hou Yubao, Gan Yanlin, Sun Hong, Guan Fei, Shao Ya, Liu Zongtao, Ou Zehu, Fan Shikai, Wang Yao, Zhai Hongjiang, Ni Chunhua, Wang Hao, Zhang Chenggang, Zhao Yan, Wang Guoping, Zhu Yuyou, Li Rui, Sun Jun, Hu Haiying, Cui Jiangping, Wang Li, Zhang Chao, Song Jianlong, Jing Xiaozhong, Wang Anmo, Wang Jinjing, Xu Pengfei, Qureshi Adnan I, Nguyen Thanh N, Nogueira Raul G, Saver Jeffrey L, Hu Wei
Department of Neurology, First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Department of Neurology, Taihe County People's Hospital, Fuyang, China.
N Engl J Med. 2025 Sep 25;393(12):1191-1201. doi: 10.1056/NEJMoa2503678. Epub 2025 Jul 4.
Intravenous thrombolysis remains a standard treatment for acute ischemic stroke within 4.5 hours after onset. Vascular reocclusion may occur after intravenous thrombolysis and may be preventable with an antiplatelet agent within the first 24 hours after thrombolysis. Tirofiban, a platelet glycoprotein IIb-IIIa receptor antagonist, has reduced macrovascular reocclusion in experimental models.
In this phase 3, multicenter, double-blind, randomized, placebo-controlled trial conducted at 38 centers in China, we assigned patients with acute ischemic noncardioembolic stroke who presented within 4.5 hours after stroke onset and who were not eligible for thrombectomy to receive a 24-hour intravenous infusion of tirofiban or placebo within 60 minutes after intravenous thrombolysis. The primary efficacy outcome was an excellent functional outcome, defined as a score of 0 to 1 on the modified Rankin scale, at 90 days. The safety outcomes were symptomatic intracranial hemorrhage within 36 hours and death at 90 days.
A total of 414 patients were assigned to receive tirofiban and 418 to receive placebo. Thrombolytic agents included alteplase (in 75% of the patients) and tenecteplase (in 25%). At 90 days, a score of 0 to 1 on the modified Rankin scale was reported in a higher percentage of patients in the tirofiban group than in the placebo group (65.9% vs. 54.9%; risk ratio, 1.20; 95% confidence interval, 1.07 to 1.34; P = 0.001). Symptomatic intracranial hemorrhage occurred in 1.7% of the patients in the tirofiban group and none in the placebo group. Mortality at 90 days was 4.1% in the tirofiban group and 3.8% in the placebo group.
In patients with acute ischemic noncardioembolic stroke who underwent thrombolysis within 4.5 hours after onset, early tirofiban increased the likelihood of an excellent functional outcome. The incidence of intracranial hemorrhage was low but higher with tirofiban than placebo. (Funded by the Fundamental Research Funds for Central Universities; ASSET-IT ClinicalTrials.gov number, NCT06134622.).
静脉溶栓仍然是急性缺血性卒中发病后4.5小时内的标准治疗方法。静脉溶栓后可能会发生血管再闭塞，并且在溶栓后的头24小时内使用抗血小板药物可能可预防这种情况。替罗非班是一种血小板糖蛋白IIb-IIIa受体拮抗剂，在实验模型中已减少了大血管再闭塞。
在中国38个中心进行的这项3期、多中心、双盲、随机、安慰剂对照试验中，我们将急性缺血性非心源性卒中且在卒中发病后4.5小时内就诊且不符合取栓条件的患者，在静脉溶栓后60分钟内分配接受替罗非班或安慰剂24小时静脉输注。主要疗效结局是90天时改良Rankin量表评分为0至1分的良好功能结局。安全性结局是36小时内的症状性颅内出血和90天时的死亡。
共414例患者被分配接受替罗非班治疗，418例接受安慰剂治疗。溶栓药物包括阿替普酶（75%的患者）和替奈普酶（25%）。90天时，替罗非班组改良Rankin量表评分为0至1分的患者百分比高于安慰剂组（65.9%对54.9%；风险比，1.20；95%置信区间，1.07至1.34；P = 0.001）。替罗非班组1.7%的患者发生症状性颅内出血，安慰剂组无。替罗非班组90天死亡率为4.1%，安慰剂组为3.8%。
在发病后4.5小时内接受溶栓治疗的急性缺血性非心源性卒中患者中，早期使用替罗非班增加了获得良好功能结局的可能性。颅内出血发生率较低，但替罗非班组高于安慰剂组。（由中央高校基本科研业务费资助；ASSET-IT临床试验注册号，NCT06134622。）
