Qureshi Adnan I, Abd-Allah Foad, Aleu Aitziber, Connors John J, Hanel Ricardo A, Hassan Ameer E, Hussein Haitham M, Janjua Nazli A, Khatri Rakesh, Kirmani Jawad F, Mazighi Mikael, Mattle Heinrich P, Miley Jefferson T, Nguyen Thanh N, Rodriguez Gustavo J, Shah Qaisar A, Siddiqui Adnan H, Suarez Jose I, Suri M Fareed K, Tolun Reha
J Vasc Interv Neurol. 2014 May;7(1):56-75.
The results of Interventional Management of Stroke (IMS) III, Magnetic Resonance and REcanalization of Stroke Clots Using Embolectomy (MR RESCUE), and SYNTHESIS EXPANSION trials are expected to affect the practice of endovascular treatment for acute ischemic stroke. The purpose of this report is to review the components of the designs and methods of these trials and to describe the influence of those components on the interpretation of trial results.
A critical review of trial design and conduct of IMS III, MR RESCUE, and SYNTHESIS EXPANSION is performed with emphasis on patient selection, shortcomings in procedural aspects, and methodology of data ascertainment and analysis. The influence of each component is estimated based on published literature including multicenter clinical trials reporting on endovascular treatment for acute ischemic stroke and myocardial infarction.
We critically examined the time interval between symptom onset and treatment and rates of angiographic recanalization to differentiate between "endovascular treatment" and "parameter optimized endovascular treatment" as it relates to the IMS III, MR RESCUE, and SYNTHESIS EXPANSION trials. All the three trials failed to effectively test "parameter optimized endovascular treatment" due to the delay between symptom onset and treatment and less than optimal rates of recanalization. In all the three trials, the magnitude of benefit with endovascular treatment required to reject the null hypothesis was larger than could be expected based on previous studies. The IMS III and SYNTHESIS EXPANSION trials demonstrated that rates of symptomatic intracerebral hemorrhages subsequent to treatment are similar between IV thrombolytics and endovascular treatment in matched acute ischemic stroke patients. The trials also indirectly validated the superiority/equivalence of IV thrombolytics (compared with endovascular treatment) in patients with minor neurological deficits and those without large vessel occlusion on computed tomographic/magnetic resonance angiography.
The results do not support a large magnitude benefit of endovascular treatment in subjects randomized in all the three trials. The possibility that benefits of a smaller magnitude exist in certain patient populations cannot be excluded. Large magnitude benefits can be expected with implementation of "parameter optimized endovascular treatment" in patients with ischemic stroke who are candidates for IV thrombolytics.
“卒中的介入治疗（IMS）III”、“使用取栓术的磁共振成像与卒中血栓再通（MR RESCUE）”及“综合扩展（SYNTHESIS EXPANSION）”试验的结果预计会影响急性缺血性卒中的血管内治疗实践。本报告旨在回顾这些试验设计与方法的组成部分，并描述这些组成部分对试验结果解读的影响。
对IMS III、MR RESCUE和SYNTHESIS EXPANSION的试验设计与实施进行批判性回顾，重点关注患者选择、操作方面的不足以及数据确定和分析方法。根据已发表的文献，包括多中心临床试验报告的急性缺血性卒中和心肌梗死的血管内治疗情况，评估每个组成部分的影响。
我们严格审查了症状发作与治疗之间的时间间隔以及血管造影再通率，以区分与IMS III、MR RESCUE和SYNTHESIS EXPANSION试验相关的“血管内治疗”和“参数优化的血管内治疗”。由于症状发作与治疗之间的延迟以及再通率未达到最佳水平，这三项试验均未能有效测试“参数优化的血管内治疗”。在这三项试验中，拒绝原假设所需的血管内治疗获益程度均大于基于先前研究的预期。IMS III和SYNTHESIS EXPANSION试验表明，在匹配的急性缺血性卒中患者中，静脉溶栓与血管内治疗后症状性脑出血的发生率相似。这些试验还间接验证了静脉溶栓（与血管内治疗相比）在轻度神经功能缺损且计算机断层扫描/磁共振血管造影无大血管闭塞患者中的优越性/等效性。
结果不支持在这三项试验中随机分组的受试者中血管内治疗有巨大获益。不能排除在某些患者群体中存在较小获益的可能性。对于适合静脉溶栓的缺血性卒中患者，实施“参数优化的血管内治疗”有望带来巨大获益。
