Advantages of Thrombectomy for Stroke with Large Central Volumes: SELECT2

Performing endovascular thrombectomy in patients ischemic stroke having a large ischemic core has been shown to be beneficial in a major international trial, which should lead to a change in clinical practice and the way stroke care systems are organised.

Results from the SELECT2 trial, which was conducted at sites in the United States, Canada, Europe, Australia and New Zealand, showed that endovascular thrombectomy combined with medical care resulted in better clinical outcomes than medical care alone in patients with a large ischemic core. who presented within 24 hours of the last time they were known to be well.

Results from the SELECT2 trial were presented today by Amrou Sarraj, MD, at the 2023 International Stroke Conference (ISC) in Dallas, Texas. Sarraj is a professor of neurology at University Hospitals Cleveland Medical Center – Case Western Reserve University in Ohio.

The study was also published simultaneously online in the New England Journal of Medicine.

A similar trial conducted in China, the ANGEL-ASPECT trialwas also presented at the same ISC session and showed very similar results.

These two lawsuits add another japanese study reported last year, the RESCUE-JAPAN LIMIT trial, also showing benefits of thrombectomy in patients with significant stroke.

Sarraj concluded that the results of these three trials taken together “unequivocally demonstrate the benefit of endovascular thrombectomy in patients with a large ischemic core.”

Approximately 20% of strokes with great vessel occlusion have a large nucleus, but these patients were not considered candidates for endovascular thrombectomy due to concerns about the potential reperfusion injury in necrotic brain tissue, leading to an increased risk of hemorrhage, edema, disability and death.

This has led to uncertainty about how to manage these patients with central infarction, Sarraj noted.

The SELECT2 trial involved patients who had suffered a stroke following an occlusion of the internal carotid artery or the first segment of the middle cerebral artery. Patients had a large ischemic central volume, defined as an Alberta Stroke Program Early Computed Tomography Score (ASPECTS) score of 3 to 5 or a central volume of at least 50 mL on imaging. They were randomly assigned to endovascular thrombectomy plus medical care or medical care alone.

The trial aimed to enroll 560 patients, but was stopped early for efficacy reasons after 178 patients were assigned to the thrombectomy group and 174 to the medical care group.

The main result – the generalized odds ratio for a change in the distribution of modified rankin scale scores toward better outcomes in favor of thrombectomy was 1.51 (P < .001).

“This translates to a 60% chance of achieving a better functional outcome in patients receiving thrombectomy, with a required number of treatments of 5. This means that 5 patients need to be treated with thrombectomy for one to achieve a better functional outcome,” Sarraj said. .

The secondary endpoint of functional independence at 90 days (score on the modified Rankin scale from 0 to 2) occurred in 20% of patients in the thrombectomy group and 7% in the medical follow-up group (relative risk, 2.97), with a number needed to be processed of 7.

Independent walking (a Modified Rankin Scale score of 0 to 3) at 90 days occurred in 37.9% of patients in the thrombectomy group and 18.7% of patients in the medical care group (relative risk, 2.06), with a number needed to be processed of 5.

Mortality was similar in both groups.

The results for the other secondary outcomes were generally in the same direction as those of the primary analysis, with the possible exception of early neurological improvement, the authors report.

The incidence of symptoms intracranial hemorrhage was low in both trial groups, occurring in one patient in the thrombectomy group and two in the medical care group.

The researchers point out that previous studies have reported rates of symptomatic intracranial hemorrhage in patients with large central ischemic lesions that are higher than those in this trial. “Therefore, the low percentage of patients with symptomatic intracranial hemorrhage observed in both trial groups was unexpected.”

Approximately 20% of patients in the thrombectomy group had complications associated with the procedure. In the thrombectomy group, complications at the arterial access site occurred in 5 patients, dissection in 10, perforation of cerebral vessels in 7, and transient vasospasm in 11.

Early neurological worsening, defined as an increase of 4 or more points on the National Institutes of Health Stroke Scale (NIHSS), occurred in 24.7% in the thrombectomy group and 15.5% in the medical care (relative risk, 1.59).

In a post-hoc analysis, “from which no conclusion can be drawn”, report the authors, early neurological worsening was associated with poorer functional outcomes at 90 days, and patients who had neurological worsening had larger ischemic lesions at baseline (median volume, 107 mL) vs 77 mL in patients without neurological worsening.

They note that a potential cause of deterioration in some of these patients was cerebral edema associated with reperfusion. However, they point out that overall, endovascular thrombectomy was associated with better outcomes than medical care alone.

“Two-thirds of patients had infarct sizes over 70ml, and one-third of patients had infarcts over 100ml, but even in patients with large and very large core volumes, thrombectomy was superior to medical care alone,” Sarraj said.

This will “change the practice”

Commenting on the study of lecoeur.org | Medscape CardiologyISC 2023 Chairman Tudor Jovin, MD, Cooper Neurological Institute, Cherry Hill, New Jersey, said, “This trial shows that even patients with large central infarcts that we would not have treated with thrombectomy in the past , actually benefit from it. And the surprise is that the benefit is almost to the same degree as that in patients with smaller core infarctions. This will change the practice.

Jovin said these findings should not only change patient selection for thrombectomy, but they should also change systems of care. “Because the care systems are now based on excluding these patients with major heart attacks. We won’t need to do that in the future.”

He explained: “I think the imaging held us back to be honest. We can rule out hemorrhage with a simple CT scan. Then after that the biggest piece of information we need from the imaging is the size of the eye. We feared that we could injure the patient if the infarction was large. Outside hospitals had to do advanced imaging before deciding to transfer patients for thrombectomy. These are all sources of delays.

“I am very happy to see these results and hope to see a much more streamlined patient triage that will be more liberal for patients with large infarcts,” he added.

Also commenting for lecoeur.org | Medscape Cardiology, Joseph Broderick, MD, professor of neurology and director of the University of Cincinnati Institute for Neuroscience, said the results were “strong and significant.”

He said the results of the SELECT2 trial, along with the two other similar trials, “will change practice and expand endovascular therapy to more severe stroke patients.”

But Broderick thinks imaging will still be needed to exclude patients with ASPECTS scores of 0 to 2, who weren’t included in these trials. “These are patients who have very large areas of clear hypodensity on the baseline image (brain already dying or dead). These patients do not benefit from reperfusion with lytic drugs or endovascular therapy,” he noted.

“Welcome News”

In a NEJM editorial support publication of the two new studies, Pierre Fayad, MD, University of Nebraska Medical Center, Omaha, points out that the three trials of thrombectomy in patients with major strokes “showed remarkably similar results” despite the differences in design, patient selection, thrombolytic therapy and dose, geographic location, and imaging criteria.

“Together, the trials provide reassuring information from more than a thousand severe ischemic stroke patients across different medical systems, which will likely lead to changes in care delivery patterns.”

Fayad says it is reasonable to suggest that endovascular thrombectomy be offered to patients with significant strokes if they arrive in a timely manner at a center capable of performing the procedure and if the patients have an ASPECTS value of 3-5. or ischemia – central volume of 50 ml or more.

Higher rates of good outcomes can be anticipated if this treatment is performed, despite increased risks of symptomatic bleeding, edema, neurological worsening and hemicraniectomy, he notes.

“Patients and families should be made aware of the limitations of treatment and the anticipated residual neurological deficits resulting from the large infarction. The improved odds of independent walking and ability to perform other daily activities in patients with the most severe strokes is good news for patients and for the field of stroke treatment,” he concludes.

The SELECT2 trial was supported by an investigator-initiated grant from Stryker Neurovascular to the University Hospitals Cleveland Medical Center and the University of Texas McGovern Medical School.

International Stroke Conference (ISC) 2023: Presentation LB21. Presented February 10, 2023.

N Eng J Med. Published online February 10, 2023. Full Text, Editorial

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