By Matthew E. Fink, MD

SOURCE: Nogueira RG, Jadhav AP, Haussen DC, et al; for the DAWN Trial Investigators. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct. N Engl J Med 2017; Nov. 11. doi: 10.1056/NEJMoa1706442. [Epub ahead of print].

At the International Stroke Conference in 2015, five separate randomized trials were reported and simultaneously published that definitively showed that endovascular thrombectomy with a stent retriever had a clinical benefit when it was performed within six hours after onset of stroke symptoms, with diminishing benefit as the interval between time of onset and thrombectomy increased. In the recently published DAWN trial, researchers studied a group of patients who had onset of symptoms more than six hours and up to 24 hours before enrollment and had a mismatch between neurological deficit and infarct size, using a novel imaging approach to determining mismatch. Many of these patients were so-called “wakeup strokes.” Patients were enrolled and divided into two groups, < 80 years or 80 years of age, and were assigned randomly to thrombectomy plus standard care or to standard care alone. The primary endpoints were the mean score for disability on a utility-weighted modified-Rankin scale, which ranges from 0 (dead) to 10 (no symptoms or disability), and the rate of functional independence using the modified-Rankin scale at 90 days.

Patients were eligible for inclusion if they had evidence of occlusion of the intracranial internal carotid artery, the first segment of the middle cerebral artery, or both, on either CT angiography or MR angiography. In addition, they had to show a mismatch between the severity of the clinical deficit and infarct volume. In the group of patients 80 years of age, a score of 10 or higher on the NIH stroke scale and infarct volume of < 21 mL indicated mismatch. In those < 80 years of age, mismatch was defined as a score of 10 or higher on the NIH stroke scale, and an infarct volume of < 31 mL. Infarct volume was measured by either diffusion-weighted MRI or perfusion CT.

A total of 206 patients were enrolled; 107 were assigned to the thrombectomy group and 99 to the control group. At 31 months, enrollment in the trial was stopped because a pre-specified interim analysis demonstrated significant differences in outcome between the groups. In the thrombectomy group, the utility-weighted modified Rankin scale at 90 days was 5.5 compared to 3.4 in the control group, with high statistical significance. The rate of functional independence at 90 days was 49% in the thrombectomy group compared with 13% in the control group, also highly statistically significant. There was no significant difference in 90-day mortality (19% vs. 18%), and the rate of symptomatic hemorrhage did not differ significantly between the groups (6% in the thrombectomy group and 3% in the control group).

In conclusion, among a group of ischemic stroke patients last known to be well six to 24 hours earlier and who had a mismatch between clinical deficit and infarct size, outcomes regarding disability and functional independence were better if treated with mechanical thrombectomy, rather than standard care alone.