Endovascular treatment for acute ischemic stroke patients: implications and interpretation of IMS III, MR RESCUE, and SYNTHESIS EXPANSION trials: a report from the Working Group of International Congress of Interventional Neurology

Abstract

Objective: 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.
Methods: 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.
Results: 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.
Conclusions: 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.