陆军军医大学（第三军医大学）第二附属医院杨清武团队，研究了急性缺血性卒中血管内再灌注后动脉内尿激酶对患者预后的影响。该研究于2025年1月13日发表于《美国医学会杂志》上。

据报道，远端动脉和微循环中持续存在或出现新血栓限制了急性缺血性卒中患者成功进行血管内血栓切除术的益处。目前尚不确定在血栓切除术接近完全再灌注后，尿激酶动脉内溶栓是否能改善大血管闭塞所致缺血性卒中患者的预后。

为了评估动脉内尿激酶在血栓切除术接近完全再灌注后治疗大血管闭塞引起的急性缺血性卒中的疗效和不良事件，这项由研究者发起的随机、开放标签、盲法终点试验在中国35家医院实施，招募了535名在24小时内出现近端颅内大血管闭塞的患者，他们通过血管内血栓切除术实现了近乎完全或完全的再灌注，并且在手术前没有接受静脉溶栓治疗。招募工作于2022年11月15日至2024年3月29日进行，最后一次随访于2024年7月4日进行。

符合条件的患者被随机分配到动脉内尿激酶组（在初始靶区注射单剂动脉内100000 IU尿激酶；n=267）或对照组（未动脉内溶栓；n=267）。主要疗效指标是患者在90天内无残疾生存的百分比（改良Rankin量表评分为0或1）。主要安全性结局是90天内的死亡率和48小时内症状性颅内出血的发生率。

共有535名患者入组（中位年龄69岁；223名[41.8%]为女性），532名（99.6%）完成了试验。动脉内尿激酶组90天无残疾生存率为45.1%（120/266），对照组为40.2%（107/266）（校正后的风险比为1.13[95%CI，0.94-1.36]；P =0.19）。90天死亡率（分别为18.4%和17.3%；校正后的危险比为1.06[95%CI，0.71-1.59]；P =0.77)、 症状性颅内出血的发生率（分别为4.1%和4.1%；校正后的风险比为1.05[95%CI，0.45-2.44]；P=0.91）在两组之间没有显著差异。

研究结果表明，在因大血管闭塞导致的急性缺血性卒中患者中，通过血管内血栓切除术进行近乎完全再灌注后，辅助动脉内尿激酶并没有显著提高90天内无残疾生存的概率。

附：英文原文

Title: Intra-Arterial Urokinase After Endovascular Reperfusion for Acute Ischemic Stroke: The POST-UK Randomized Clinical Trial

Author: Chang Liu, Changwei Guo, Fengli Li, Nizhen Yu, Jiacheng Huang, Zhouzhou Peng, Weilin Kong, Jiaxing Song, Xiang Liu, Shitao Fan, Chengsong Yue, Boyu Chen, Chong Zheng, Xingyun Yuan, Jian Sheng, Youlin Wu, Bo Sun, Zengqiang Zhao, Minzhen Zhu, Ling Han, Qiang Shi, Zhongbin Xia, Xianjin Shang, Fengguang Li, Rongzong Li, Feixue Yue, Shunfu Jiang, Dengwen Song, Min Song, Yuanjun Shan, Chawen Ding, Li Yao, Yong Yang, Junbin Chen, Wencheng He, Feibao Pan, Wensheng Zhang, Tieying Cai, Shibo Han, Wei Li, Gongbo Li, Chen Gong, Liping Huang, Cheng Huang, Duolao Wang, Johannes Kaesmacher, Thanh N. Nguyen, Raul G. Nogueira, Jeffrey L. Saver, Wenjie Zi, Yangmei Chen, Qingwu Yang, POST-UK investigators, Tao Qiu, Yihong Huang, Dai Zheng, Zhongyong Peng, Sizhi Tang, Chuang Li, Rongtong Li, Yongtao Guo, Chaoxiong Shen, Xiurong Zhu, Yugang Wang, Lei Zhang, Haitao Guan, Tao Xu, Jie Yang, Linyu Li, Dahong Yang, Jinfu Ma, Xu Xu, Xiaolei Shi

Issue&Volume: 2025-01-13

Abstract:

Importance  Persisting or new thrombi in the distal arteries and the microcirculation have been reported to limit the benefits of successful endovascular thrombectomy for patients with acute ischemic stroke. It remains uncertain whether intra-arterial thrombolysis by urokinase following near-complete to complete reperfusion by thrombectomy improves outcomes among patients with ischemic stroke due to large vessel occlusion.

Objective  To assess the efficacy and adverse events of intra-arterial urokinase after near-complete to complete reperfusion by thrombectomy for acute ischemic stroke due to large vessel occlusion.

Design, Setting, and Participants  This investigator-initiated, randomized, open-label, blinded–end point trial was implemented at 35 hospitals in China, enrolling 535 patients with proximal intracranial large vessel occlusion presenting within 24 hours of time last known well, who achieved near-complete or complete reperfusion by endovascular thrombectomy and did not receive intravenous thrombolysis prior to the procedure. Recruitment took place between November 15, 2022, and March 29, 2024, with final follow-up on July 4, 2024.

Interventions  Eligible patients were randomly assigned to the intra-arterial urokinase group (a single dose of intra-arterial 100000 IU urokinase injected in the initial target territory; n=267) or control group (without intra-arterial thrombolysis; n=267).

Main Outcomes and Measures  The primary efficacy outcome was the percentage of patients achieving survival without disability (modified Rankin Scale score of 0 or 1) at 90 days. The primary safety outcomes were mortality at 90 days and incidence of symptomatic intracranial hemorrhage within 48 hours.

Results  A total of 535 patients were enrolled (median age, 69 years; 223 [41.8%] female) and 532 (99.6%) completed the trial. The percentage of patients with survival without disability at 90 days was 45.1% (120/266) in the intra-arterial urokinase group and 40.2% (107/266) in the control group (adjusted risk ratio, 1.13 [95% CI, 0.94-1.36]; P=.19). Mortality at 90 days (18.4% vs 17.3%, respectively; adjusted hazard ratio, 1.06 [95% CI, 0.71-1.59]; P=.77) and incidence of symptomatic intracranial hemorrhage (4.1% vs 4.1%, respectively; adjusted risk ratio, 1.05 [95% CI, 0.45-2.44]; P=.91) were not significantly different between groups.

Conclusions and Relevance  Among patients with acute ischemic stroke due to large vessel occlusion, adjunct intra-arterial urokinase after near-complete to complete reperfusion by endovascular thrombectomy did not significantly increase the likelihood of survival without disability at 90 days.

DOI: 10.1001/jama.2024.23480

Source: https://jamanetwork.com/journals/jama/fullarticle/2829204