替奈普酶治疗发病 4.5 至 24 小时内的缺血性脑卒中且未进行取栓治疗。

Tenecteplase for Ischemic Stroke at 4.5 to 24 Hours without Thrombectomy.

机构信息

From the Department of Neurology (Y. Xiong, Y.J., L. Zong, M.H., Z.C., Liyuan Wang, S.W., Z.L., X.Z., Y.W.), the China National Clinical Research Center for Neurologic Diseases (Y. Xiong, X.M., A.J., Y.J., Y.P., C.D., W.Y., H.L., Y.W.), and the Advanced Innovation Center for Human Brain Protection (Y.W.), the Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, and the Research Unit of Artificial Intelligence in Cerebrovascular Disease, Chinese Academy of Medical Sciences (Y.W.), Beijing, the Department of Neurology, Linyi People's Hospital, Linyi (F.C., H.W., Z.W.), the Department of Neurology, Second Affiliated Hospital of Harbin Medical University, Harbin (Lihua Wang), the Department of Neurology, Weifang People's Hospital, Weifang (L. Zhou), the Department of Emergency Medicine, Linfen Central Hospital, Linfen (H.D.), the Department of Neurology, Guangdong Second Provincial General Hospital, Guangzhou (X.L.), the Department of Neurology, First Affiliated Hospital of Zhengzhou University, the National Health Commission Key Laboratory of Prevention and Treatment of Cerebrovascular Disease, Zhengzhou (Y. Xu), the Department of Neurology, First Affiliated Hospital of Jinan University, Guangzhou (A.X.), and the Department of Neurology, First People's Hospital of Foshan, Foshan (Z.T.) - all in China; the Department of Medicine and Neurology, Royal Melbourne Hospital, University of Melbourne, Parkville, VIC (B.C.V.C), and the Department of Neurology, University of New South Wales South Western Sydney Clinical School, Liverpool (M.W.P.) - both in Australia; Yale New Haven Health System, Yale School of Medicine, New Haven, CT (L.H.S.); and the Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston (M.F.).

出版信息

N Engl J Med. 2024 Jul 18;391(3):203-212. doi: 10.1056/NEJMoa2402980. Epub 2024 Jun 14.

DOI:10.1056/NEJMoa2402980

PMID:38884324

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 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 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. (Funded by the National Natural Science Foundation of China and others; TRACE-III ClinicalTrials.gov number, NCT05141305.).

摘要

背景

替奈普酶是一种有效的溶栓药物，适用于在卒中发作后 4.5 小时内接受治疗的符合条件的卒中患者。然而，关于替奈普酶在 4.5 小时后应用的有效性的数据有限。

方法

在中国进行的一项试验中，我们将符合条件的大脑中动脉或颈内动脉大血管闭塞、通过灌注成像确定有可挽救脑组织且无法进行血管内血栓切除术的患者随机分为两组，一组接受替奈普酶（剂量为 0.25 毫克/千克体重；最大剂量 25 毫克）治疗，另一组接受标准药物治疗，两组治疗时间均为患者最后一次已知状态良好（包括卒中后觉醒和未目击到的卒中）后 4.5 至 24 小时。主要结局是 90 天时无残疾，即改良 Rankin 量表评分为 0 或 1（范围为 0 至 6，评分越高表示残疾越严重）。关键安全性结局是症状性颅内出血和死亡。

结果

共纳入 516 例患者，其中 264 例随机分配至替奈普酶组，252 例分配至标准药物治疗组。不到 2%的患者（替奈普酶组 4 例，标准治疗组 5 例）接受了补救性血管内血栓切除术。90 天时，替奈普酶组改良 Rankin 量表评分为 0 或 1 的患者比例高于标准药物治疗组（33.0% vs. 24.2%；相对风险，1.37；95%置信区间，1.04 至 1.81；P=0.03）。替奈普酶组 90 天死亡率为 13.3%，标准药物治疗组为 13.1%，替奈普酶组治疗后 36 小时内症状性颅内出血的发生率为 3.0%，标准药物治疗组为 0.8%。

结论

在这项涉及中国因大血管闭塞导致缺血性卒中的患者的试验中，大多数患者未接受血管内血栓切除术，与标准药物治疗相比，在卒中发作后 4.5 至 24 小时内使用替奈普酶治疗可降低残疾程度和提高生存率，且症状性颅内出血的发生率似乎更高。（由国家自然科学基金等资助；TRACE-III ClinicalTrials.gov 编号，NCT05141305）。