澳大利亚墨尔本大学Peter J Mitchell比较了脑卒中发病4.5小时内行血管内血栓切除术与标准桥接溶栓加血管内血栓切除术的疗效和安全性。相关论文于2022年7月9日发表在《柳叶刀》杂志上。

血管内血栓切除术前静脉溶栓联合治疗对大血管闭塞引起的急性缺血性卒中患者的临床益处尚不明确。研究组假设，脑卒中大血管闭塞患者在4.5小时内直接行血管内血栓切除术治疗的临床效果不低于标准桥接治疗（血管内血栓切除术前静脉溶栓）。

研究组进行了一项国际性、多中心、前瞻性、随机、开放标签、盲法终点试验，从澳大利亚、新西兰、中国和越南的25家急诊医院招募了经非对比CT和血管成像证实的脑卒中合并颅内颈内动脉、大脑中动脉（M1或M2）或基底动脉大血管闭塞的成年患者，这些患者脑卒中发病均不到4.5小时。

研究组通过基于网络的计算机生成的随机程序，按基线动脉闭塞部位和地理区域分层，将符合条件的患者随机分配（1:1），以指导血管内血栓切除术或桥接治疗。根据每个机构的标准护理，接受桥接治疗的患者接受静脉溶栓治疗（阿替普酶或替萘普酶）；血管内血栓切除术也符合护理标准，使用Trevo装置作为一线干预。

评估结果的人员不清楚小组分配；患者和治疗医生知情。主要疗效终点是功能独立性，定义为改良Rankin量表评分0-2分或在90天时恢复到基线，非劣效边缘为-0.1，根据治疗意向（包括所有随机分配和同意的患者）和每个方案进行分析。安全性分析包括意向治疗人群。

2018年6月2日至2021年7月8日，研究组共招募了295名患者，将其随机分组，其中直接血管内血栓切除组148例，桥接治疗组147例。直接血栓切除组146例患者中有80例（55%）出现功能独立性，桥接治疗组147例患者中89例（61%），意向治疗风险差为-0.051，按方案风险差为-0.062。

组间安全性结局相似，直接血栓切除组146例患者中有2例（1%）出现症状性脑出血，桥接治疗组147例患者中有1例（1%），校正后的优势比为1.70；直接血栓切除组146例患者中有22例（15%）死亡，桥接治疗组147例患者中有24例（16%）死亡，校正后的优势比为0.92。

研究结果表明，与桥接疗法相比，该研究未显示出直接血管内血栓切除术的非劣效性。研究中的额外信息应为指导原则提供信息，以推荐桥接疗法作为标准治疗。

附：英文原文

Title: Endovascular thrombectomy versus standard bridging thrombolytic with endovascular thrombectomy within 4·5 h of stroke onset: an open-label, blinded-endpoint, randomised non-inferiority trial

Author: Peter J Mitchell, Bernard Yan, Leonid Churilov, Richard J Dowling, Steven J Bush, Andrew Bivard, Xiao Chuan Huo, Guoqing Wang, Shi Yong Zhang, Mai Duy Ton, Dennis J Cordato, Timothy J Kleinig, Henry Ma, Ronil V Chandra, Helen Brown, Bruce C V Campbell, Andrew K Cheung, Brendan Steinfort, Rebecca Scroop, Kendal Redmond, Ferdinand Miteff, Yan Liu, Dang Phuc Duc, Hal Rice, Mark W Parsons, Teddy Y Wu, Huy-Thang Nguyen, Geoffrey A Donnan, Zhong Rong Miao, Stephen M Davis, Patricia Desmond, Nawaf Yassi, Henry Zhao, Cameron Williams, Fana Alemseged, Felix C Ng, Vignan Yogendrakumar, Peter Bailey, Laetitia De Villiers, Thanh Phan, Tharani Thirugnanachandran, Winston Chong, Hamed Asadi, Lee Anne Slater, Nathan Manning, Jason Wenderoth, Alan McDougall, Cameron Williams, Cecilia Cappelen-Smith, Justin Whitley, Leon Edwards, Carlos Garcia Esperon, Neil Spratt, Elizabeth Pepper, Chris Levi, Ken Faulder, Timothy Harrington, Martin Krause, Michael Waters, John Fink, Gaoting Ma, Xiangpeng Shen, Xiangkong Song, Yonglei Gao, Nam Guangxian, Zaiyu Guo, Heliang Zhang, Hongxing Han, Hao Wang, Geng Liao, Zhenyu Zhang, Chaomao Li, Zhi Yang, Chuwei Cai, Chuming Huang, Yifan Hong

Issue&Volume: 2022/07/09

Abstract:

Background

The benefit of combined treatment with intravenous thrombolysis before endovascular thrombectomy in patients with acute ischaemic stroke caused by large vessel occlusion remains unclear. We hypothesised that the clinical outcomes of patients with stroke with large vessel occlusion treated with direct endovascular thrombectomy within 4·5 h would be non-inferior compared with the outcomes of those treated with standard bridging therapy (intravenous thrombolysis before endovascular thrombectomy).

Methods

DIRECT-SAFE was an international, multicentre, prospective, randomised, open-label, blinded-endpoint trial. Adult patients with stroke and large vessel occlusion in the intracranial internal carotid artery, middle cerebral artery (M1 or M2), or basilar artery, confirmed by non-contrast CT and vascular imaging, and who presented within 4·5 h of stroke onset were recruited from 25 acute-care hospitals in Australia, New Zealand, China, and Vietnam. Eligible patients were randomly assigned (1:1) via a web-based, computer-generated randomisation procedure stratified by site of baseline arterial occlusion and by geographic region to direct endovascular thrombectomy or bridging therapy. Patients assigned to bridging therapy received intravenous thrombolytic (alteplase or tenecteplase) as per standard care at each site; endovascular thrombectomy was also per standard of care, using the Trevo device (Stryker Neurovascular, Fremont, CA, USA) as first-line intervention. Personnel assessing outcomes were masked to group allocation; patients and treating physicians were not. The primary efficacy endpoint was functional independence defined as modified Rankin Scale score 0–2 or return to baseline at 90 days, with a non-inferiority margin of –0·1, analysed by intention to treat (including all randomly assigned and consenting patients) and per protocol. The intention-to-treat population was included in the safety analyses. The trial is registered with ClinicalTrials.gov, NCT03494920, and is closed to new participants.

Findings

Between June 2, 2018, and July 8, 2021, 295 patients were randomly assigned to direct endovascular thrombectomy (n=148) or bridging therapy (n=147). Functional independence occurred in 80 (55%) of 146 patients in the direct thrombectomy group and 89 (61%) of 147 patients in the bridging therapy group (intention-to-treat risk difference –0·051, two-sided 95% CI –0·160 to 0·059; per-protocol risk difference –0·062, two-sided 95% CI –0·173 to 0·049). Safety outcomes were similar between groups, with symptomatic intracerebral haemorrhage occurring in two (1%) of 146 patients in the direct group and one (1%) of 147 patients in the bridging group (adjusted odds ratio 1·70, 95% CI 0·22–13·04) and death in 22 (15%) of 146 patients in the direct group and 24 (16%) of 147 patients in the bridging group (adjusted odds ratio 0·92, 95% CI 0·46–1·84).

Interpretation

We did not show non-inferiority of direct endovascular thrombectomy compared with bridging therapy. The additional information from our study should inform guidelines to recommend bridging therapy as standard treatment.

DOI: 10.1016/S0140-6736(22)00564-5

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)00564-5/fulltext