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《柳叶刀》(The Lancet)发表一项基于中心影像裁定的系统评价与个体患者数据Meta分析,旨在评估发病24小时内就诊的缺血性卒中伴大面积梗死核心患者接受取栓治疗的获益,并基于临床及影像亚组分析疗效差异。结果表明,相对于内科治疗组,血管内取栓组在发病90天时的mRS评分分布得到改善,且死亡率更低。同时,血管内取栓未增加症状性颅内出血和神经功能恶化风险,其获益在大多数亚组中保持一致。识别文中二维码或点击文末“阅读原文”,查阅原文。

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发病24小时内就诊的缺血性卒中伴大面积梗死核心患者行血管内取栓治疗(ATLAS研究):基于中心影像裁定的系统评价与个体患者数据Meta分析

背景

既往关于卒中患者血管内取栓治疗的研究常把存在大面积缺血病灶的患者排除在外。本研究通过系统评价及个体患者数据(individual patient data, IPD)Meta分析,整合近年相关临床试验证据,评估此类患者接受取栓治疗的获益,并基于临床及影像亚组分析疗效差异。

方法

本系统评价与Meta分析检索了PubMed和Embase数据库,筛选2018年3月1日至2025年3月1日期间发表的随机对照试验;纳入发病24小时内就诊、缺血性卒中伴大面积梗死核心的患者(Alberta卒中项目早期CT评分ASPECTS≤5分,或预估缺血核心体积≥50mL),对比血管内取栓与单纯内科治疗的有效性及安全性。从符合纳入标准的试验获取个体患者数据。由中心影像核心实验室对影像资料进行重新判读,包括ASPECTS评分的复核以及缺血核心体积的再分析。疗效分析采用两阶段随机效应模型进行Meta分析,主要结局指标为90天时改良Rankin量表(modified Rankin Scale, mRS)评分的分布情况,以校正合并广义比值比(adjusted pooled generalized odds ratio, aGenOR)估算效应量。通过多重插补法处理缺失数据。安全性终点包括:随机分组后90天内全因死亡率以及24–48小时内神经功能恶化,以校正合并相对风险aRR估算;随机分组后36小时内症状性颅内出血,以风险率差估算。此外,根据临床及影像学特征进行亚组分析,包括按缺血核心体积、ASPECTS评分以及发病至随机分组时间窗进行分层。本研究已在PROSPERO注册(注册号:CRD420251058584)。

结果

共纳入6项随机试验,共1886例患者,其中944例接受血管内取栓治疗,942例接受内科治疗。两组基线特征基本均衡。发病90天时,相对于内科治疗组,血管内取栓组的mRS评分分布得到改善(取栓组中位评分4分(四分位距3–6分,n=940)vs.内科组5分(4–6分,n=931;校正合并广义比值比=1.63(95%CI:1.42–1.88,P<0.0001)。取栓组90天死亡率更低(取栓组31.1%(292例)vs.内科组37.3%(347例),校正相对风险=0.82(95%CI:0.70–0.97,P=0.022)。在安全性方面,两组症状性颅内出血(取栓组1.1%(10/944)vs.内科组1.0%(9/942),非校正合并风险差−0.17个百分点(95%CI−1.01to0.67),p=0.69)和神经功能恶化(197/896 [22.0%]vs161/899[17.9%];aRR1.19[95%CI0.87–1.62],p=0.27)均无统计学差异。在亚组分析中,血管内取栓对功能结局的改善左右在大多数临床与影像学亚组中与主分析结果保持一致。在缺血核心体积≥150mL的患者亚组中,虽然效应量的点估计结果提示血管内取栓可能更优,尤其是在发病0–6小时内,但由于其95%置信区间较宽,限制了对结果确定性的解读。
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图1 90天随访时改良Rankin量表(mRS)评分的分布

解读

对于发病后24小时内的缺血性卒中伴大面积梗死核心患者,与单纯内科治疗相比,血管内取栓可显著改善远期功能预后并降低死亡率。除缺血范围极大(缺血核心体积≥150mL)且发病超过6小时的患者证据仍有限外,对于发病24小时内,具有不同ASPECTS 评分及不同缺血核心体积分层的患者,均可从血管内取栓中获益END

Funding

None.


Declaration of interests

AJY declares grants and contracts paid to their institution from Medtronic, Cerenovus, Penumbra, Stryker, Genentech, Balt, and Route 92; consulting fees from Penumbra, Vesalio, and NIH/NINDS; participation on a data safety and monitoring board or advisory board with Route 92 and HCA Neurovascular Research Advisory Board; and stock or stock options in Insera Therapeutics, Galaxy Medical, Gravity Medical, and Nicolab. AEH declares consulting fees from Medtronic, Microvention, Stryker, Penumbra, J&J MedTech, Genentech, GE Healthcare, Scientia, Balt, Viz.ai, Insera therapeutics, Proximie, NeuroVasc, NovaSignal, Vesalio, Rapid Medical, Imperative Care, Galaxy Therapeutics, Route 92, Perfuze, CorTech, Imago, Shockwave, Toro, NeuroVasX, Xcath, Kaneka, Plaga, Project Neu, Piraeus, BioPhiliQ, Arbor Medical, Medinol, Navigantis, and Magnisity; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Medtronic, Microvention, Stryker, Penumbra, J&J MedTech, Genentech, GE Healthcare, Scientia, Balt, Viz.ai, Insera therapeutics, Proximie, NeuroVasc, NovaSignal, Vesalio, Rapid Medical, Imperative Care, Galaxy Therapeutics, Route 92, Perfuze, CorTech, Imago, Shockwave, Toro, NeuroVasX, Xcath, Kaneka, Plaga, Project Neu, Piraeus, BioPhiliQ, Arbor Medical, Medinol, Navigantis, and Magnisity; participation on a data safety and monitoring board for the COMAND trial and FOCUS trial; and being Past President of the Society of Vascular and Interventional Neurology. AS declares grant support as a global principal investigator (PI) for SELECT LATE (Patient-Centered Outcomes Research Institute; paid to their institution) and as a PI for SELECT, SELECT2, and Stryker Neurovascular (paid to their institution). AR declares consulting fees from Stryker NV, Cerenovous, Route 92; and participation on a data safety and monitoring board for ATHENA and TORNADO. BG declares grant support from the French Ministry of Health as a PI for TITAN, DIRECT ANGIO, and IA-SUCCESS; consulting fees from Air Liquide, MIVI, Medtronic, Microvention, Perfuze, and Penumbra; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Boehringer Ingelheim, Acticor Biotech, Medtronic, and Penumbra. BL declares grants or contracts from Balt, Microvention, and Phenox; and consulting fees from Olea Medical. CA declares consulting fees from Medtronic; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Medtronic. CM declares grants or contracts from the European Union, CVON/Dutch Heart Foundation, Boehringer Ingelheim, and Stryker (paid to their institution); and stock or stock options from Nicolab (minority interest). CZS declares grants or contracts from the Health Research Foundation of Central Denmark Region (research grant from hospital); and participation on a data safety monitoring board or advisory board for EAST-STROKE. DSL declares consulting fees for imaging core laboratory work from Johnson & Johnson and Rapid Medical. DD declares participation on a data and safety monitoring committee for ACT Global, and, in the past, data and safety monitoring committee for TESLA; and role as Vice Chair of the data access committee of CONTRAST consortium. GM declares consulting fees from Stryker, Terumo Neuro, and Sim & Cure; payment for lectures for Penumbra, Medtronic, Wallaby Phenox, Cerenovus (Johnson & Johnson), and Bracco; and participation on an advisory board for the MAESTRO study. GT declares (related to the current manuscript) receipt of funding for the TENSION trial from the EU Horizon 2020 Research and Innovation Programme under grant agreement number 754640; consulting fees from Acandis, Bayer, Boehringer Ingelheim, and TarGED; payment or honoraria from Acandis, Boehringer Ingelheim, and Lilly; and role as Chair of the Board of Directors of the European Stroke Organisation. HY declares payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Daiichi-Sankyo, Otsuka Pharmaceutical, Stryker, Boston Scientific, Abbott Medical (lecture fee, personal). JCG declares research grants from Genentech (supplies investigational product); consulting fees from Frazer (consulting on mobile stroke unit); payment for expert testimony from various law firms (legal malpractice cases) three times in 2026; support for attending meetings and/or travel from Perosphere (consulting meeting); participation as chair of a data safety monitoring board for Prolong Pharma. JF declares, for the current project, role as managing director of EppData (completed imaging core laboratory work for TENSION trial); consulting fees (personal) from Medtronic, Stryker, Microvention/Terumo, Cerenovus/JuJ Medtech, Acandis, Phenox, and Penumbra; support for attending meetings and/or travel from Microport; participation on a data safety monitoring board or advisory board for Stryker and Phenox; role as Past President of ESMINT; and stock or stock options for Eppdata and Vastrax. MJ declares consulting fees for advisory boards for BMS and Bayer. MB declares grants from EU Horizon 2020 for the TENSION trial, the EU for the VALIDATE trial, and the DFG for SFB project C02; payment or honoraria for educational talks for Novartis and Boehringer Ingelheim; and role as Editor in Chief for Clinical Neuroradiology (Springer). MC declares consulting fees from RapidPulse and Route 92; payment for expert testimony from various law firms; participation on a data safety monitoring board or advisory board for STEM; and role as Editor of Journal of NeuroInterventional Surgery. MDH declares grants or contracts from NoNO (grant to the University of Calgary for the ESCAPE-NA1 trial, ESCAPE NEXT trial), Canadian Institutes for Health Research (grant to the University of Calgary for the ESCAPE-NA1 trial, ESCAPE NEXT trial, and ACT-GLOBAL trial), Medtronic (grant to the University of Calgary for the ESCAPE-MeVO study), and Boehringer Ingelheim (grant to the University of Calgary for ACT-GLOBAL trials); consulting fees from Sun Pharma (for adjudication of clinical trials outcomes); patents planned, issued, or pending (US Patent 62/086,077, licensed to Circle NVI; and US Patent 10 916,346, licensed to Circle NVI); participation as data and safety monitoring committee chair for ONCOVIR Hiltonel trial, DUMAS trial, EMAGINE trial, EVERLAST trial, ILLUMINATE trial, and POTENTIAL trial; participation as data safety monitoring board member for the ARTESIA trial, BRAIN-AF trial, and LAOOS trial; role as President of the Canadian Neurological Sciences Federation (not for profit); stock or stock options in Circle Inc and Basking Biosciences (private stock or stock options). RG declares consulting fees from Medtronic, Balt, Cerenovus, Kaneka, and Stryker Neurovascular. SY declares payment or honoraria for lectures from Daiichi Sankyo, Bristol Myers Squibb, Otsuka Pharmaceutical, Stryker, Medtronic, Johnson & Johnson, Kaneka Medics, Terumo, Medicos Hirata, Nxera Pharma, and Eisai. SAS declares consulting fees (personal) from Penumbra, Route 92, Perfuze, Balt, and Kaneka; support for attending meetings and/or travel from the American Heart Association and the German Neuroradiology Society; and participation on a data safety monitoring board or advisory board for Vesalio (clinical events committee participation). SBo declares funding for the present manuscript from EU Horizon 2020 and EU Horizon 2.1. TM declares other financial interests, outside the submitted work, in Abbott, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eisai, GlaxoSmithKline, Integra LifeSciences, Pfizer, UCB, Japan Lifeline. TGJ declares grants or contracts from NIH (STEP), PCORI, and Stryker; consulting fees from Medtronic, Johnson & Johnson, and Contego Medical; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Medtronic; participation on a data safety monitoring board or advisory board for Johnson and Johnson; and stock or stock options in Route 92, Viz.ai, Methinks, Gravity, Galaxy, Anaconda, Kandu, FreeOx Biotech, and Vastrax. WS declares participation on a data safety monitoring board for the PICASSO Trial, SEGA Trial, TESLA Trial, TESSERACT-2 Trial, and role as safety adjudicator for the SISTER trial. RGN reports research grants from Cerenovus and Stryker Neurovascular to the University of Pittsburgh; role as a principal investigator of the “Endovascular Therapy for Low NIHSS Ischemic Strokes (ENDOLOW)” trial (funding provided by Cerenovus); role as a principal investigator of the “Combined Thrombectomy for Distal MediUm Vessel Occlusion StroKe (DUSK)” trial (funding provided by Stryker Neurovascular); consulting fees for advisory roles with Anaconda, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, J&J, Cerenovus, Genentech, Philips, Hybernia, Hyperfine, Imperative Care, Medtronic, Merck, Phenox, Prolong Pharmaceuticals, Stryker Neurovascular, Shanghai Wallaby, Synchron, Takeda Pharmaceutical; stock options for advisory roles with Astrocyte, Brainomix, Cerebrotech, Ceretrieve, Corindus Vascular Robotics, CrestecBio, Euphrates Vascular, Vesalio, Viz.ai, RapidPulse, Sensome, and Perfuze; and being an investor in Viz.ai, Perfuze, Cerebrotech, Reist/Q’Apel Medical, Truvic, Tulavi Therapeutics, Vastrax, Piraeus Medical, Brain4Care, Quantanosis AI, Unity Medical, and Viseon. SOG reports research grants from NIH/NINDS, PCORI, Stryker, Medtronic, and Methinks; consulting fees from Stryker and Medtronic; payment or honoraria from Stryker and Medtronic; appointment as president of the Society of Vascular and Interventional Neurology; and stock options and equity in Motif, Gravity, and Clotter. TNN reports consulting fees as an advisor for Bayer, Route 92, and Medtronic; and appointment as Associate Editor for Stroke. All other authors declare no competing interests.



题图 Copyright: Halfpoint Images via GettyImages       

中文翻译仅供参考,所有内容以英文原文为准。

DOI: 10.1016/S0140-6736(26)00876-7 


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