Literature Review

Thrombectomy at Six to 24 Hours After Stroke May Improve Outcomes


Compared with standard care alone, standard care plus endovascular thrombectomy at six to 24 hours after stroke onset appears to reduce disability and increase functional independence among patients with a mismatch between clinical deficit and infarct. These findings, which were published online ahead of print November 11 in the New England Journal of Medicine, could benefit patients with stroke who arrive at the hospital after the current six-hour treatment window has closed, said the authors.

“When the irreversibly damaged brain area affected by the stroke is small, we see that clot removal can make a significant positive difference, even if performed outside the six-hour window,” said Tudor Jovin, MD, Director of the University of Pittsburgh Medical Center Stroke Institute. “However, this does not diminish the urgency with which patients must be rushed to the emergency room in the event of a stroke. The mantra ‘time is brain’ still holds true.”

Tudor Jovin, MD

The DAWN Trial Examined Late Thrombectomy

Previous research has indicated that thrombectomy provides clinical benefits for patients with acute ischemic stroke when it is performed within six hours of symptom onset. The benefit of treatment appeared to decrease as the time to treatment increased. Nonrandomized studies, however, have shown that reperfusion of occluded proximal anterior cerebral vessels improves outcomes in patients with a mismatch between the volume of brain tissue that may be salvaged and the volume of infarcted tissue, even if performed more than six hours after the patient was last known to be well.

Dr. Jovin and colleagues conducted the DAWN trial, a multicenter, prospective, randomized, open-label study, to evaluate the effects of late thrombectomy. Eligible patients had an occlusion of the intracranial internal carotid artery or proximal middle cerebral artery and had last been known to be well six to 24 hours earlier. Patients either did not meet criteria for treatment with IV alteplase because of late presentation, or had persistent vessel occlusion despite treatment with IV alteplase.

Participants also had a mismatch between the severity of the clinical deficit and the infarct volume, which was assessed using diffusion-weighted MRI or perfusion CT. The investigators sorted mismatches into three groups. Group A included patients age 80 or older with an NIH Stroke Scale (NIHSS) score of 10 or higher and an infarct volume of less than 21 mL. Group B included patients younger than 80 with an NIHSS score of 10 or higher and an infarct volume of less than 31 mL. Group C included patients younger than 80 with an NIHSS score of 20 or higher and had an infarct volume between 31 mL and 51 mL.

The investigators randomized participants to thrombectomy plus standard care or standard care alone. The first primary end point was the mean score for disability on the utility-weighted modified Rankin scale, which ranges from 0 (ie, death) to 10 (ie, no symptoms or disability). The second was the rate of functional independence (ie, a score of 0–2 on the modified Rankin scale) at 90 days. The main safety end point was stroke-related death at 90 days.

Enrollment Was Halted Early

Dr. Jovin and colleagues enrolled 206 patients in the trial. Enrollment was stopped at 31 months, because an interim analysis found that thrombectomy plus standard care was 95% likely to be superior to standard care alone for the first primary end point. In all, 107 patients received thrombectomy plus standard care, and 99 received standard care alone.

Participants’ mean age was 70, and approximately 46% of participants were men. Median NIHSS score was 17, and median infarct volume was 8.25 mL. The treatment arms were generally balanced, except for three factors. History of atrial fibrillation and wake-up stroke were more common in the thrombectomy group, and treatment with IV alteplase was more common in the control group.

The mean utility-weighted modified Rankin scale score at 90 days was 5.5 in the thrombectomy group and 3.4 in the control group. The rate of functional independence at 90 days was 49% in the thrombectomy group and 13% in the control group. The superiority of thrombectomy plus standard treatment to standard treatment alone for both end points remained significant in post hoc sensitivity analyses that adjusted for between-group differences in baseline characteristics.

The rate of stroke-related death at 90 days did not differ significantly between the treatment groups. Nor did the rate of death from any cause at 90 days or the rate of symptomatic intracerebral hemorrhage differ significantly between groups. The rate of neurologic deterioration was lower in the thrombectomy group than in the control group.

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