Influence of time to endovascular stroke treatment on outcomes in the early versus extended window paradigms

Background: The effect of time from stroke onset to thrombectomy in the extended time window remains poorly characterized.

Aim: We aimed to analyze the relationship between time to treatment and clinical outcomes in the early versus extended time windows.

Methods: Proximal anterior circulation occlusion patients from a multicentric prospective registry were categorized into early (≤6 h) or extended (>6-24 h) treatment window. Patients with baseline National Institutes of Health Stroke Scale (NIHSS) ≥ 10 and intracranial internal carotid artery or middle cerebral artery-M1-segment occlusion and pre-morbid modified Rankin scale (mRS) 0-1 ("DAWN-like" cohort) served as the population for the primary analysis. The relationship between time to treatment and 90-day mRS, analyzed in ordinal (mRS shift) and dichotomized (good outcome, mRS 0-2) fashion, was compared within and across the extended and early windows.

Results: A total of 1603 out of 2008 patients qualified. Despite longer time to treatment (9[7-13.9] vs. 3.4[2.5-4.3] h, p < 0.001), extended-window patients (n = 257) had similar rates of symptomatic intracranial hemorrhage (sICH; 0.8% vs. 1.7%, p = 0.293) and 90-day-mortality (10.5% vs. 9.6%, p = 0.714) with only slightly lower rates of 90-day good outcomes (50.4% vs. 57.6%, p = 0.047) versus early-window patients (n = 709). Time to treatment was associated with 90-day disability in both ordinal (adjusted odd ratio (aOR), ≥ 1-point mRS shift: 0.75; 95%CI [0.66-0.86], p < 0.001) and dichotomized (aOR, mRS 0-2: 0.73; 95%CI [0.62-0.86], p < 0.001) analyses in the early- but not in the extended-window (aOR, mRS shift: 0.96; 95%CI [0.90-1.02], p = 0.15; aOR, mRS0-2: 0.97; 95%CI [0.90-1.04], p = 0.41). Early-window patients had significantly lower 90-day functional disability (aOR, mRS shift: 1.533; 95%CI [1.138-2.065], p = 0.005) and a trend towards higher rates of good outcomes (aOR, mRS 0-2: 1.391; 95%CI [0.972-1.990], p = 0.071).

Conclusions: The impact of time to thrombectomy on outcomes appears to be time dependent with a steep influence in the early followed by a less significant plateau in the extended window. However, every effort should be made to shorten treatment times regardless of ischemia duration.