ENCORE! Getting to the core of the ischemic core at the core lab

David S. Liebeskind, Scott Brown, Albert J. Yoo
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Abstract

The recent results of large core trials in acute ischemic stroke prompt the most influential paradigm shift in over a decade since endovascular therapy (EVT) was proven as the mainstay of acute stroke treatment. Six randomized, controlled trials (RCTs) of EVT in patients with more extensive ischemia on imaging than prior approved treatment indications revealed a consistent benefit of EVT, despite different imaging criteria and ischemic core definitions across the individual trials. These findings unfolded sequentially, akin to the acts of a drama, with the story evolving until perhaps the most conclusive results on extensive ischemia treatment about to be published. At this juncture, it is important to summarize the collective findings of these 6 RCTs, consider the potential expansion in the use of EVT, outline the penultimate or next steps during the encore of this drama and ponder the broad implications of these recent findings on the entire stroke field for many years to come. This logical rationale and perspective form the basis of Establishing Neuroimaging Criteria of Revascularization Efficacy (ENCORE), the proposed pooled, subject-level, meta-analysis of the recent large core trials, leveraging imaging re-adjudication by a collaborative, imaging core lab with documented expertise. Expansion of the treatment indications for EVT will likely ensue, yet numerous questions persist regarding other confounding variables that we normally use in routine clinical practice. Precision medicine for large core ischemic stroke mandates a more detailed investigation of the numerous clinical, imaging and angiographic variables that each trial dataset collected. In a simple pooled meta-analysis, these varying definitions, methodology and analytic approaches preclude anything beyond current summary results showing that EVT is favored, in general, over medical treatment. The epilog of the large core trials can be written by ENCORE, using the imaging and statistical methods and relevant expertise of the prior Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials (HERMES) collaboration.
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ENCORE!在核心实验室获取缺血核心的核心信息
自血管内治疗(EVT)被证明是急性卒中治疗的主要方法以来,最近对急性缺血性卒中的大型核心试验结果促使十多年来最具影响力的模式转变。六项随机对照试验(RCT)显示,尽管各试验的成像标准和缺血核心定义不同,但对成像显示缺血范围大于先前批准的治疗适应症的患者进行 EVT 治疗的获益是一致的。这些研究结果依次展开,就像戏剧中的一幕幕情节,故事不断发展,直到即将发表关于广泛缺血治疗的最确凿的结果。在此时刻,我们有必要总结一下这 6 项临床试验的集体发现,考虑扩大 EVT 使用范围的可能性,概述这场戏剧的倒数第二幕或接下来的步骤,并思考这些最新发现对未来许多年整个中风领域的广泛影响。这一逻辑原理和观点构成了《建立血管再通疗效的神经影像学标准》(ENCORE)的基础,ENCORE 是对近期大型核心试验进行的受试者级别的汇总荟萃分析,由具有专业技术的影像学核心实验室合作进行影像学再判断。EVT的治疗适应症可能会随之扩大,但对于我们在常规临床实践中通常使用的其他混杂变量,仍存在许多问题。针对大核心缺血性卒中的精准医疗要求对每个试验数据集收集的众多临床、影像和血管造影变量进行更详细的调查。在简单的汇总荟萃分析中,这些不同的定义、方法学和分析方法使得除了目前的总结结果表明 EVT 总体上优于药物治疗之外,无法得出其他结论。大型核心试验的后记可由 ENCORE 利用成像和统计方法以及之前多个血管内卒中试验中评估的高效再灌注(HERMES)合作项目的相关专业知识来撰写。
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