By Matthew E. Fink, MD
Professor and Chairman,
Department of Neurology,
Weill Cornell Medical College,
New York Presbyterian Hospital

Dr. Fink reports he is a consultant for Procter & Gamble.

SOURCES: Berkhemer OA, et al. for the MR CLEAN investigators. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med 2015;372:11-20. DOI: 10.1056/NEJMoa1411587

Goyal M, et al, for the ESCAPE trial investigators. Randomized assessment of rapid endovascular treatment of ischemic stroke. New Engl J Med 2015;372:1019-1030. DOI: 10.1056/NEJMoa1414905.

Campbell BC, et al, for the EXTEND-IA investigators. Endovascular therapy for ischemic stroke with perfusion-imaging selection. New Engl J Med 2015;372:1009-1018. DOI: 10.1056/NEJMoa1414792.

In last month’s Neurology Alert, we briefly mentioned the studies reported at the International Stroke Conference that showed dramatic improvements in neurological outcome and survival using the latest intracranial clot retrieval devices. This month, we will discuss three studies that have been recently published in the New England Journal of Medicine — MR CLEAN, ESCAPE, and EXTEND — regarding intracranial clot extraction for acute ischemic stroke.

In MR CLEAN, 500 patients from 16 medical centers in the Netherlands were enrolled and randomized to usual care vs intracranial clot extraction. Eligible patients had a proximal arterial occlusion in the anterior cerebral circulation confirmed by vessel imaging that could be treated intra-arterially within 6 hours of symptom onset. The primary outcome was the modified Rankin scale score in 90 days. Mean age of the patients was 65 years, and 89% were treated with intravenous alteplase before randomization. Retrieval stents were used and 81.5% of the patients assigned to intra-arterial treatment. The adjusted odds ratio for a good functional outcome was 1.67 (95% confidence interval [CI], 1.21-2.30). There was an absolute difference of 13.5 percentage points in favor of functional independence (modified Rankin score 0-2) in the interventional group (32.6% vs 19.1%). There was no significant difference in mortality or the occurrence of symptomatic intracerebral hemorrhage between the two groups of patients.

In the ESCAPE trial, participants with acute ischemic stroke in the anterior circulation with a demonstrated proximal vessel occlusion were included up to 12 hours after symptom onset. Patients with a large infarct core or poor collateral circulation on CT and CT angiography were excluded. The primary outcome was the score on the modified Rankin scale at 90 days.

The trial was stopped early because of efficacy. At 22 centers around the world, 316 participants were enrolled and 238 received intravenous alteplase before any interventions. The median time from study CT to the first reperfusion in the interventional group was 84 minutes. The rate of functional independence (90-day modified Rankin score of 0-2) was improved with the intervention (53% vs 29%, P ≤ 0.001). The primary outcome measure favored the intervention group with an odds ratio of 2.6. The intervention was associated with reduced mortality compared to the control group, but there was no significant difference in the rate of symptomatic intracerebral hemorrhage.

Finally, in the EXTEND-IA trial, patients were randomly assigned to receive standard intravenous alteplase, with or without endovascular thrombectomy, using the SOLITAIRE FR stent retriever. Patients were enrolled if they presented within 4.5 hours after onset of ischemic stroke symptoms. All patients had occlusion of the internal carotid or middle cerebral artery and evidence of salvageable brain tissue with a small ischemic core, based on CT perfusion imaging. The primary outcomes were reperfusion in 24 hours and early neurological improvement (8-point reduction on the NIHSS or score = 0 to 1 at day 3). Secondary outcomes included the modified Rankin scale score at 90 days. The trial was stopped early because of efficacy after 70 patients had undergone randomization. The percentage of ischemic territory that had undergone reperfusion in 24 hours was greater in the endovascular therapy group compared to the alteplase only group, and endovascular therapy, initiated at a median of 210 min., increased early neurological improvement at 3 days (80% vs 37%, P = 0.002). More patients had improved functional outcome and 90 days (71% vs 40%). There were no differences in rates of death or symptomatic intracerebral hemorrhage.

All three of these well-designed and executed studies support the efficacy of intracranial artery clot extraction for patients with acute ischemic stroke, who have 1) proven major vessel occlusion, 2) short time interval between onset of symptoms and start of the procedure, and 3) use of the most advanced technological devices. Improved technology and patient selection played a major role in determining the success of these trials, and these rules should be applied when making treatment decisions for our own patients. These studies, and others, are heralding a new era in ischemic stroke therapy.