Endovascular therapy for acute ischemic stroke is indicated and evidence based: a position statement.

In February 2013, three prospective randomized controlled trials were published simultaneously in the New England Journal of Medicine—the Interventional Management of Stroke (IMS III), Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE), and SYNTHESIS-Expansion trials. Each of these studies demonstrated no benefit for endovascular intervention over medical management for patients with acute ischemic stroke (AIS). However, these trials suffered from significant design flaws which were largely related to a very slow rate of patient enrollment, and resulted in the subsequent obsolescence of the imaging protocols and devices used. Recently, the Multicenter Randomized CLinical trial of Endovascular treatment for AIS in the Netherlands (MR CLEAN), a prospective randomized controlled trial of 500 patients comparing endovascular therapies with medical management for patients with large vessel occlusion (LVO), presented their results at the 9th World Stroke Congress (Istanbul, Turkey 2014). Unlike IMS III and SYNTHESISExpansion, LVO was confirmed prior to randomization in all patients. Also, in contrast with MR RESCUE, IMS-III, and SYNTHESIS-Expansion, modern thrombectomy devices were used for the entirety of the trial. Primary and secondary outcomes in MR CLEAN demonstrated a significant benefit for endovascular therapies over medical therapy across all age groups. Furthermore, a second ongoing prospective randomized trial of AIS patients with LVO, Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE), was recently halted by its data safety monitoring board due to the ‘overwhelming efficacy’ of intra-arterial thrombolysis (IAT) over medical therapy in a preliminary analysis performed in response to the results of MR CLEAN. Similarly, the phase 2 EXTEND-IA trial was halted when a preliminary analysis of the data demonstrated overwhelming efficacy in the interventional cohort. Completion of these three trials has moved the dial forward on the value of mechanical thrombectomy. A critical and evidence based evaluation of the available data supports the superiority of IAT over standard medical therapies in patients presenting with AIS from LVO within 6 h of stroke onset and having a small infarct core. Moreover, we believe that randomization of these patients in trials, which include a non-interventional arm, may no longer be ethical as general community equipoise appropriately disappears. An examination of the available data is certainly needed to identify those patient populations where equipoise may still exist. In this subset, additional research trials may be informative. The purpose of this comment is to explain this position based on a rigorous review of the available evidence, historical precedents established in the medical treatment of AIS, and important ethical considerations.