ESCAPE Trial Supports Rapid Endovascular Thrombectomy in the Management of Large-Vessel Acute Ischemic Stroke

Intravenous thrombolysis has remained the mainstay treatment for patients with acute ischemic stroke for the past 2 decades. Although thrombolysis using intravenous tissue plasminogen activator (IV tPA) improves outcome in select patients, the clinical application of this treatment is limited by a short therapeutic window and numerous contraindications. Furthermore, IV tPA has been shown to be much less effective at recanalizing large-vessel occlusions such as the internal carotid or the M1 segment of the middle cerebral artery. In 1999, the randomized, controlled, multicenter clinical trial Prolyse in Acute Cerebral Thromboembolism II (PROACT II) demonstrated a significant improvement in the modified Rankin Scale (mRS) of enrolled patients after administration of intra-arterial prourokinase (40% vs 25% in the control group).1 In an effort to achieve more consistent and rapid reperfusion, mechanical thrombectomy devices were subsequently developed and have been used extensively and effectively to treat large-vessel occlusions. Unfortunately, in 2013, the SYNTHESIS, MR RESCUE, and International Management of Stroke-3 (IMS-3) trials suggested that endovascular treatment resulted in no significant benefit in patient outcome compared with standard of care (IV tPA alone).2-4 The largest of the 3 trials, IMS-3, enrolled 656 patients (434 patients to the IV tPA followed by endovascular treatment and 222 to IV tPA alone) at 58 centers.4 This trial was stopped prematurely because of futility. Proponents of mechanical thrombectomy put forth several criticisms of these 3 published trials, citing a relatively long delay before endovascular treatment, the absence of pretreatment vascular imaging to confirm a large-vessel occlusion, and limited use of newer-generation thrombectomy devices. The Endovascular Treatment of Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial is a recently published trial demonstrating the robust clinical benefit of mechanical thrombectomy for proximal large-vessel occlusions. ESCAPE was a multicenter, prospective, randomized, controlled trial that used vascular imaging (computed tomographic [CT] angiography) to confirm a large-vessel occlusion before patient enrollment.5 Adult stroke patients without an upper age limit who were functionally independent at baseline were enrolled up to 12 hours after symptom onset. Noncontrast head CT or multiphase CT angiography was used to evaluate core infarct size with the Alberta Stroke Program Early CT Score (ASPECTS) scale.6 Between February 2013 and October 2014, 22 centers (Canada [11], the United States [6], South Korea [3], Ireland [1], and the United Kingdom [1]) randomized 316 participants (165 to intervention and 150 to the control), of which 238 received IV tPA (120 vs 118 in the intervention vs control group, respectively). Shortly after the results of the Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN) trial were announced, ESCAPE was stopped prematurely by the data and safety monitoring board because of a perceived lack of equipoise in the population of patients with large-vessel occlusion. This occurred despite the fact that MR CLEAN used much broader inclusion criteria, represented only a single country’s treatment results, and had low requirements for interventionalists.7,8 At the 90-day mRS analysis, the results of ESCAPE demonstrated a common odds ratio of 2.6 in favor of the intervention arm (P < .001), with a median mRS score at 90 days of 2.0 vs 4.0 in the intervention vs the control cohort, respectively (P < .001; Figure).Figure: Scores on the modified Rankin Scale at 90 days in the intervention-to-treat population. Scores on the modified Rankin Scale range from 0 to 6: 0 = no symptoms, 1 = clinically significant disability, 2 = slight disability, 3 = moderate disability, 4 = moderately severe disability, 5 = severe disability, and 6 = death. A, the distribution of scores at 90 days in the intervention and control groups in the overall trial population. A significant difference between the intervention and control groups was noted in the overall distribution of scores (unadjusted common odds ratio, indicating the odds of improvement of 1 point on the modified Rankin Scale, 2.6; 95% confidence interval, 1.7-3.8), favoring the intervention. B, the distribution of scores at 90 days in the intervention and control groups according to status with respect to intravenous alteplase treatment. In this analysis, there was no evidence of heterogeneity of effect (P = .80 for interaction by the Wald test). From New England Journal of Medicine, Goyal M, Demchuk AM, Menon BK, et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. Copyright © 2015 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society. 5The percentage of patients who exhibited a 90-day mRS score of 0 to 2 was 53% in the intervention group compared with 29.3% in the control group (P < .001). There was no significant difference in symptomatic intracerebral hemorrhage between the 2 groups (3.6% vs 2.7% in the control group; P = .75). A significant decrease in mortality at 90 days was observed (19% in the control arm vs 10.4% in the intervention arm; P = .04). Furthermore, there were no differences in outcome if IV tPA was given to patients undergoing intervention. Finally, with a median time of 84 minutes from first imaging to reperfusion, ESCAPE suggested that faster reperfusion times may improve clinical outcomes. Even though ESCAPE was stopped prematurely, the results are compelling, given that the improvement in the common odds ratio exceeded that of MR CLEAN (2.6 vs 1.6, respectively).5,7 The ESCAPE trial demonstrated that, for patients with an acute proximal anterior circulation occlusion documented on pretreatment imaging, a small infarct core, and moderate to good collateral circulation, rapid endovascular treatment with retrievable stents led to decreased mortality and significantly improved clinical outcome. A potential limitation remains the generalizability of these results given the stringent requirements for rapid reperfusion that might not be achievable at all interventional stroke centers. Nevertheless, taken in the context of the recently published positive results of both MR CLEAN and EXTEND-IA, it is now clear that large-vessel ischemic stroke should be regarded as a multidisciplinary surgical disease for which medical management alone is suboptimal.7,9 Neurointerventionalists and stroke neurologists should thus work synergistically and systems of care must be streamlined to achieve optimal outcomes in the setting of a significant anticipated increase in endovascular patient treatment volume.

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