麻豆传媒

Late thrombectomy can still work for some stroke patients that fit a certain profile, according to an interim analysis of a randomized trial.

Investigators of the DAWN trial randomized 206 patients presenting 6-24 hours after ischemic stroke onset (a group with occlusions of the intracranial internal carotid artery, or proximal middle cerebral artery) to standard care with or without endovascular thrombectomy. Notably, these patients all had a clinical deficit that was disproportionately severe given their small infarct core on MRI or perfusion CT.

At 90 days, average disability scores on the utility-weighted modified Rankin scale (5.5 vs 3.4 for control, adjusted difference 2.0 points, 95% CI 1.1-3.0 point difference). Rates of functional independence per the modified Rankin scale also revealed a clear advantage with intervention (49% vs 13%, adjusted absolute difference 33%, 95% CI 24-44%), according to Tudor Jovin, MD, of University of Pittsburgh Medical Center Stroke Institute, and DAWN trial colleagues.

The data were presented at the Society of Vascular and Interventional Neurology meeting in Boston, and published simultaneously in the New England Journal of Medicine.

Safety outcomes were no different between groups: whether patients got thrombectomy or not, their chances of developing symptomatic intracranial hemorrhaging (6% vs 3%, P=0.50) or dying at 90 days (19% vs 18%, P=1.00) were statistically indistinguishable.

This means a safety profile for thrombectomy that was the same within 6 hours and in the 6-24-hour period, Jovin's group suggested.

It was also a notable finding that 90-day functional independence was 49% with late endovascular intervention, comparable to the 46% derived from a prior pooling of five thrombectomy trials in which patients predominantly received treatment within 6 hours after stroke onset, they said.

Then again, this could be because just 14% got IV alteplase in DAWN (since patients presented after the typical window that it is given) and not 88% like those prior trials, the authors acknowledged

"The DAWN trial gives us hope that trials investigating the use of late IV thrombolysis that require the presence of ischemic tissue might have positive outcomes," said Werner Hacke, MD, PhD, DSc, of Germany's University of Heidelberg, anticipating results of the WAKE-UP, ECASS-4 EXTEND, EXTEND, and DEFUSE 3 trials.

In an , Hacke commented that DAWN participants were selected specifically because they had a region of brain that was poorly perfused but not yet infarcted. "In essence, the usual 6-hour time window for stroke treatment was replaced with a 'tissue window,'" he said.

Does this mean a tissue window is just as good as a time window when gauging if endovascular therapy will work?

Hacke cautioned that the results of DAWN "do not support a general liberalization of the time window for thrombectomy or thrombolysis. Reducing the time from the onset of stroke to treatment remains essential and results in the best outcomes."

"It is likely that a limited proportion of patients with occlusion of a large vessel who present late after the onset of stroke will have a small infarct core and a large volume of tissue at risk, as did the patients in the DAWN trial. For those patients, late thrombectomy works -- but as of now, as far as we know, it works only for them," according to the editorialist.

DAWN was stopped at 31 months upon a prespecified review of interim data. Data analysis was performed by staff from Stryker Neurovascular, the sponsor of the study and a big player in the stent retriever space.

By the time of randomization, the thrombectomy and control groups had had 12.2 and 13.3 hours pass since the last time they were known to be well -- more than half first had symptoms upon waking up. Median infarcts were 7.6 ml and 8.9 ml, respectively. Both groups started treatment with a NIH Stroke Scale score of 17.

There were baseline differences between arms despite randomization; for one, thrombectomy patients were more likely to have a history of atrial fibrillation. But adjusting for these differences did not change the main findings of the main trial, Jovin's group noted.

The benefit of thrombectomy was consistent across prespecified subgroups, but the power of the trial to assess differences between subgroups was limited, the DAWN investigators stated.