北京天坛医院王拥军教授团队研究了替萘普酶治疗缺血性卒中症状发作后4.5至24小时内患者的疗效与安全性。相关论文于2024年6月14日发表在《新英格兰医学杂志》上。

替萘普酶是一种有效的溶栓剂，适用于在脑卒中发作后4.5小时内接受治疗的符合条件的中风患者。然而，关于替萘普酶超过4.5小时有效性的数据是有限的。

在中国进行的一项试验中，研究组随机分配了大脑中动脉或颈内动脉大血管闭塞的患者，这些患者在灌注成像中发现有可挽救的脑组织，并且无法进行血管内血栓切除术，在患者最后一次确认健康后的4.5至24小时内（包括苏醒时的中风和未经麻醉的中风后）接受替萘普酶（剂量为每公斤体重0.25 mg；最大剂量为25 mg）或标准药物治疗。主要结局是在第90天没有残疾，这被定义为改良Rankin量表上的0或1分（范围为0到6分，分数越高表示残疾越严重）。关键的安全性结局是症状性颅内出血和死亡。

共有516名患者入组；264名被随机分配接受替萘普酶治疗，252名接受标准药物治疗。不到2%的患者（替萘普酶组4例，标准治疗组5例）接受了抢救性血管内血栓切除术。替萘普酶治疗导致90天时改良Rankin量表评分为0或1的患者比例高于标准药物治疗（33.0%对24.2%；相对比率为1.37；95%置信区间为1.04至1.81；P=0.03）。替萘普酶治疗90天时的死亡率为13.3%，标准药物治疗为13.1%，治疗后36小时内症状性颅内出血的发生率分别为3.0%和0.8%。

研究结果表明，在这项涉及中国因大血管闭塞而缺血性脑卒中患者的试验中，大多数患者没有接受血管内血栓切除术，与标准药物治疗相比，在脑卒中发作后4.5至24小时内给予替萘普酶治疗可减少残疾，并保持相似的生存率，但症状性颅内出血的发生率似乎更高。

附：英文原文

Title: Tenecteplase for Ischemic Stroke at 4.5 to 24 Hours without Thrombectomy

Author: Yunyun Xiong, Bruce C.V. Campbell, Lee H. Schwamm, Xia Meng, Aoming Jin, Mark W. Parsons, Marc Fisher, Yong Jiang, Fengyuan Che, Lihua Wang, Li Zhou, Hongguo Dai, Xintong Liu, Yuesong Pan, Chunmiao Duan, Yuming Xu, Anding Xu, Lixia Zong, Zefeng Tan, Wanxing Ye, Hao Wang, Ziran Wang, Manjun Hao, Zhixin Cao, Liyuan Wang, Shuangzhe Wu, Hao Li, Zixiao Li, Xingquan Zhao, Yongjun Wang

Issue&Volume: 2024-06-14

Abstract:

BACKGROUND

Tenecteplase is an effective thrombolytic agent for eligible patients with stroke who are treated within 4.5 hours after the onset of stroke. However, data regarding the effectiveness of tenecteplase beyond 4.5 hours are limited.

METHODS

In a trial conducted in China, we randomly assigned patients with large-vessel occlusion of the middle cerebral artery or internal carotid artery who had salvageable brain tissue as identified on perfusion imaging and who did not have access to endovascular thrombectomy to receive tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or standard medical treatment within 4.5 to 24 hours after the time that the patient was last known to be well (including after stroke on awakening and unwitnessed stroke). The primary outcome was the absence of disability, which was defined as a score of 0 or 1 on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability), at day 90. The key safety outcomes were symptomatic intracranial hemorrhage and death.

RESULTS

A total of 516 patients were enrolled; 264 were randomly assigned to receive tenecteplase and 252 to receive standard medical treatment. Less than 2% of the patients (4 in the tenecteplase group and 5 in the standard-treatment group) underwent rescue endovascular thrombectomy. Treatment with tenecteplase resulted in a higher percentage of patients with a modified Rankin scale score of 0 or 1 at 90 days than standard medical treatment (33.0% vs. 24.2%; relative rate, 1.37; 95% confidence interval, 1.04 to 1.81; P=0.03). Mortality at 90 days was 13.3% with tenecteplase and 13.1% with standard medical treatment, and the incidence of symptomatic intracranial hemorrhage within 36 hours after treatment was 3.0% and 0.8%, respectively.

CONCLUSIONS

In this trial involving Chinese patients with ischemic stroke due to large-vessel occlusion, most of whom did not undergo endovascular thrombectomy, treatment with tenecteplase administered within 4.5 to 24 hours after stroke onset resulted in less disability and similar survival as compared with standard medical treatment, and the incidence of symptomatic intracranial hemorrhage appeared to be higher.

DOI: NJ202406140000008

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2402980