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Reference: DAWN trial (N Engl J Med 2017 Nov 11 early online) (level 2 [mid-level] evidence)
- Endovascular therapy with a stent retriever may be considered up to 6 hours after onset of ischemic stroke. The potential benefit of thrombectomy after 6 hours is unclear.
- The DAWN trial evaluated thrombectomy 6-24 hours after stroke onset plus standard care vs. standard care alone in 206 adults with ischemic stroke who had evidence of salvageable brain tissue indicated by clinical deficits disproportionately severe compared to infarct volume.
- Addition of thrombectomy to standard care increased the likelihood of functional independence (modified Rankin Scale score ≤ 2) at 90 days (in 49% vs. 13% with standard care alone, p < 0.001, NNT 3).
For patients with acute ischemic stroke, the American Heart Association/American Stroke Association (AHA/ASA) guidelines recommend endovascular therapy with stent retriever in adults meeting specific stroke assessment criteria and in whom treatment can be initiated within 6 hours of stroke onset (Stroke 2015). Evidence regarding the benefit of thrombectomy after 6 hours is limited as previous trials (REVASCAT trial-N Engl J Med 2015 and ESCAPE trial-N Engl J Med 2015) had only a small percentage of patients undergoing thrombectomy at ≥ 6 hours after stroke onset. To address whether reperfusion > 6 hours after stroke onset may reduce functional deficits, the DAWN trial evaluated 206 adults (mean age 70 years) with occlusion of the intracranial internal carotid or proximal middle cerebral artery who met specific criteria indicating disproportionately severe clinical deficits compared to infarct volume, and who were last known to be well 6-24 hours previously. Infarct volume was determined by automated measurement of images obtained with diffusion-weighted magnetic resonance imaging or perfusion computed tomography. Enrolled patients either presented too late for IV alteplase or had persistent occlusion after IV alteplase. The patients were randomized to thrombectomy with the Trevo retrievable self-expanding stent plus standard care vs. standard care alone. Investigators blinded to treatment allocation assessed functional outcomes using the modified Rankin Scale (mRS) (range 0-6 with 6 indicating death) and a utility-weighted mRS score (range 0-10 with 0 indicating death). The trial was terminated early at the first interim analysis based on a prespecified stopping rule.
At baseline, the thrombectomy group had significantly more patients with onset of stroke on awakening (in 63% vs. 47% with standard care, p = 0.03) and a history of atrial fibrillation (in 40% vs. 24% with standard care, p=0.01), and significantly fewer patients treated with IV alteplase (in 5% vs. 13% with standard care, p = 0.04). The median interval from the last time the patient was known well and randomization was 12.2 hours in the thrombectomy group and 13.3 hours in the standard care group. The addition of thrombectomy to standard care increased the likelihood of functional independence defined as mRS score ≤ 2 (in 49% with thrombectomy vs. 13% with standard care alone, p < 0.001, NNT 3) and resulted in better functional scores at 90 days on the utility-weighted mRS (5.5 points with thrombectomy vs. 3.4 points with standard care alone, p < 0.001). There were no significant differences in rates of all-cause death, stroke-related death, and symptomatic intracranial hemorrhage between the groups. Complications related to thrombectomy occurred in 7% of patients.
The DAWN trial demonstrated that thrombectomy 6-24 hours after stroke in addition to standard care improved functional outcomes in patients with occlusion of the intracranial internal carotid or proximal middle cerebral artery who had disproportionately severe clinical deficits compared to infarct volume. The baseline differences between the groups adds some uncertainty to the findings. The results of this trial are derived from a precisely-defined group of patients with acute ischemic stroke and the identification of patients for whom delayed thrombectomy is feasible may be hampered by the limited availability of the imaging techniques employed. In addition, it is unclear what proportion of patients with acute ischemic stroke may meet the selection criteria for this trial as the number of patients screened for eligibility was not provided. In summary, the findings from the DAWN trial suggest that the window for thrombectomy may be extended up to 24 hours after ischemic stroke onset in a select group of patients.
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