Olthuis Susanne G H, Pinckaers Florentina M E, Robbe M M Quirien, de Ridder Inger R, Hoving Jan W, Venema Esmee, Daems Jasper D, Pirson F A V Anne, Staals Julie, Emmer Bart J, Lingsma Hester F, Roosendaal Stefan D, van der Hoorn Anouk, Koopman Miou S, Postma Alida A, Dippel Diederik W J, Majoie Charles B, van Oostenbrugge Robert J, van Zwam Wim H
Department of Neurology, Maastricht University Medical Centre+, Maastricht, the Netherlands.
School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands.
JAMA Neurol. 2025 May 5. doi: 10.1001/jamaneurol.2025.0716.
MR CLEAN-LATE (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands for Late Arrivals) showed efficacy of endovascular treatment (EVT) in the late window (6-24 hours after stroke symptom onset or time last seen well) among patients with ischemic stroke selected based on collateral flow. Therefore, the future role of computed tomography perfusion (CTP) imaging in patient selection for late-window EVT may change.
To investigate the interaction among CTP parameters (core volumes, penumbra volumes, and mismatch ratio) and the association of EVT with functional outcomes among patients in the late window after ischemic stroke selected based on collateral flow.
DESIGN, SETTING, AND PARTICIPANTS: This is a post hoc secondary analysis of MR CLEAN-LATE, a multicenter randomized clinical trial, with open-label treatment and blinded end point, conducted from February 2, 2018, to January 27, 2022, in 18 Dutch stroke intervention centers. Participants included 502 patients with anterior circulation large vessel occlusion and present collateral flow on results of computed tomographic angiography in the late window after stroke, who gave deferred consent and were included in MR CLEAN-LATE. All patients had completed follow-up at 90 days. This secondary analysis included 313 patients (62%) with available CTP results. Statistical analysis was performed in September 2023.
Patients were randomized to receive EVT (EVT group) and best medical management vs best medical management alone (no EVT group).
The primary outcome was functional outcome at 90 days measured by the modified Rankin Scale score. The treatment effect was analyzed in subgroups of core volumes, penumbra volume, and mismatch ratios using ordinal regression analysis. An interaction analysis was performed to assess whether CTP parameters modified the EVT effect on the modified Rankin Scale score at 90 days. All analyses were adjusted for relevant prognostic factors.
Among the 313 patients (158 women [50%]) in the study, the median age was 73 years (IQR, 63-80 years), and the EVT group had fewer male participants than the no EVT group (73 of 168 [43%] vs 82 of 145 [57%]). Penumbra volumes significantly modified the association of EVT with outcomes (P < .001 for interaction), with the largest effect size among patients with penumbras of 120 mL or more (adjusted common odds ratio [ACOR], 6.89 [95% CI, 2.96-16.04]) and the smallest effect size among patients with penumbras of 72 mL or less (ACOR, 0.49 [95% CI, 0.22-1.08]). Core volume and mismatch ratio did not modify the EVT effect.
Based on results from this secondary analysis of the MR CLEAN-LATE randomized clinical trial, there was a direct interaction between penumbra volume and treatment effect, and a trend toward potential harm of EVT was seen among patients with the smallest penumbras, which warrants further research. However, core volume and mismatch ratio did not seem to have additional value in patient selection.
isrctn.org Identifier: ISRCTN19922220.
MR CLEAN-LATE（荷兰急性缺血性卒中血管内治疗多中心随机临床试验，针对延迟就诊患者）显示，在基于侧支血流选择的缺血性卒中患者中，血管内治疗（EVT）在延迟时间窗（卒中症状发作后或最后一次看起来状态良好的时间6至24小时）具有疗效。因此，计算机断层扫描灌注（CTP）成像在延迟时间窗EVT患者选择中的未来作用可能会改变。
探讨基于侧支血流选择的缺血性卒中患者在延迟时间窗内CTP参数（梗死核心体积、半暗带体积和不匹配率）之间的相互作用以及EVT与功能结局的关联。
设计、设置和参与者：这是对MR CLEAN-LATE的事后二次分析，MR CLEAN-LATE是一项多中心随机临床试验，采用开放标签治疗和盲法终点，于2018年2月2日至2022年1月27日在18个荷兰卒中干预中心进行。参与者包括502例前循环大血管闭塞且在卒中延迟时间窗的计算机断层血管造影结果显示存在侧支血流的患者，他们给予了延迟同意并被纳入MR CLEAN-LATE。所有患者均完成了90天的随访。这项二次分析纳入了313例（62%）有可用CTP结果的患者。统计分析于2023年9月进行。
患者被随机分为接受EVT（EVT组）加最佳药物治疗与仅接受最佳药物治疗（非EVT组）。
主要结局是90天时用改良Rankin量表评分测量的功能结局。使用有序回归分析在梗死核心体积、半暗带体积和不匹配率亚组中分析治疗效果。进行交互分析以评估CTP参数是否改变了EVT对90天时改良Rankin量表评分的影响。所有分析均针对相关预后因素进行了调整。
在该研究的313例患者（158例女性[50%]）中，中位年龄为73岁（四分位间距，63 - 80岁），EVT组男性参与者少于非EVT组（168例中的73例[43%]对145例中的82例[57%]）。半暗带体积显著改变了EVT与结局的关联（交互作用P < .001），在半暗带体积为120 mL或更大的患者中效应量最大（调整后的共同优势比[ACOR]，6.89 [95% CI，2.96 - 16.04]），在半暗带体积为72 mL或更小的患者中效应量最小（ACOR，0.49 [95% CI，0.22 - 1.08]）。梗死核心体积和不匹配率未改变EVT效果。
基于对MR CLEAN-LATE随机临床试验的这项二次分析结果，半暗带体积与治疗效果之间存在直接相互作用，并且在半暗带体积最小的患者中观察到EVT有潜在危害的趋势，这值得进一步研究。然而，梗死核心体积和不匹配率在患者选择中似乎没有额外价值。
isrctn.org标识符：ISRCTN19922220。
