Intraarterial Treatment for Acute Ischemic Stroke

Published - Written by Chana Sacks

She knew the signs.

When Mary suddenly dropped her coffee cup because all of the strength in her right arm disappeared and her speech became garbled, she knew that she was having a stroke.  A wise 78-year-old, Mary couldn’t remember where she had learned these warning signs – was it from from her doctor? A friend? Something on TV? – but she realized that she had to get to a hospital.  Her husband called 9-1-1, and she was transported to the Emergency Department.

Suspecting that Mary was correct in the diagnosis, the Emergency Department physician urgently paged the neurology team, while rushing her into the CT scanner. A non-contrast head CT showed no intracranial bleed, and less than 90minutes after the onset of her first symptom, thrombolytics were pushed through the IV in her arm.  A CT angiogram ultimately confirmed that an occlusion in the middle cerebral artery was indeed the culprit.  While the care Mary had received up to this point had been efficient and consistent with the latest evidence, the question remained: could anything else be done to improve her chance of a good functional outcome?

This was precisely the question that the MR CLEAN investigators posed in a new trial of intraarterial treatment, now published in NEJM.   Prior to this study, intravenous alteplase administered within 4.5 hours of stroke onset was the only proven effective reperfusion therapy for acute ischemic strokes. The MR CLEAN researchers sought to examine whether intraarterial treatment – defined as intraarterial thrombolysis, mechanical thrombectomy, or both – improved outcomes. The data from this trial offer reasons to believe that we may be entering a new era in the treatment of acute ischemic strokes.

This phase 3 trial included 500 adults from 16 centers in the Netherlands who were randomized to either usual care plus intraarterial treatment or usual care alone.  All participants had an acute ischemic stroke caused by a proximal occlusion of the anterior cerebral circulation demonstrated on vessel imaging, had a score of 2 or greater on the NIH Stroke Scale, and could undergo intraarterial treatment within 6 hours of stroke onset.   Importantly, usual care could include the use of intravenous thrombolytics, and 89% of patients received IV alteplase prior to randomization.   The mean age of participants in the trial was 65 years.  There was no upper age limit, and in fact, the oldest patient in the study was 96.

The data show a significant improvement in functional outcomes for participants in the intraarterial treatment arm: at 90 days, 32.6% of participants in the intervention arm were functionally independent (with a score of 2 points or less on the modified Rankin that measures functional outcomes) as compared with 19.1% in the usual care arm [absolute difference 13.5 percentage points, 95% CI 5.9 to 21.2].  No significant difference was observed in the rates of mortality or symptomatic intracranial hemorrhage.  However, at 90 days, 13 of 233 patients (5.6%) in the intraarterial treatment group had signs of a new ischemic stroke in a different vascular territory, as compared with only 1 of 267 patients (0.4%) in the control arm.

In an accompanying editorial, Dr. Werner Hacke poses the critical question.  He asks, “Is there any doubt left, or should thrombectomy now become the new standard treatment for severe stroke with proximal large-vessel occlusion up to 6 hours after stroke onset?” In the end, he seems cautiously optimistic but suggests that further data will be critical. Putting it all in context, he calls this trial, “the first step in the right direction.”

Back to Mary – as intraarterial treatment is not currently the standard of care, it seems likely that the hospital where she presented will hope that IV thrombolysis is enough to restore her highly functional baseline.  However, if further trials that are already underway confirm the results found here, we may soon be able to do more to stave off the potentially devastating effects of large ischemic strokes.

For more on MR CLEAN, view the Quick Take video summary.

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