Extended Window for Stroke Thrombectomy

Abstract

Objective: Mechanical thrombectomy is the standard treatment for large vessel occlusion (LVO) in acute ischemic stroke (AIS) up to 6 h after onset. Recent trials have demonstrated a benefit for wake-up strokes and patients beyond 6 h.

Methods: A systematic literature review was conducted for multicenter randomized clinical trials (RCTs) investigating endovascular stroke treatment using perfusion imaging to identify patients that may benefit from mechanical thrombectomy for AIS beyond 6 h of onset. Random effects meta-analysis was used to analyze the following outcomes: 90-day functional independence rates with modified Rankin Scale (mRS ≤2), 90-day mortality, and symptomatic intracranial hemorrhage (sICH) rates. Further stratification was carried out by age and presentation.

Results: Two multicenter RCT's were included as follows: DAWN and DEFUSE-3. Pooled 90-day functional independence rates favored endovascular management (odds ratio [OR] 5.01; P < 0.00001). Subgroup analysis demonstrated continued 90-day functional independence benefit for endovascular management regardless of age (≥80 years, OR 5.65, P = 0.01; ≤80 years, OR 4.92, P < 0.00001). When stratified for the manner of stroke discovery, 90-day functional independence rates favored endovascular management for wake-up strokes (OR 8.74, P < 0.00001) and known-time onset strokes (OR 5.08, 95% confidence interval [CI] 2.04-12.65, P = 0.0005), although no benefit was observed for unwitnessed strokes (OR 1.64, 95% CI 0.17-16.04, P = 0.67). No difference observed in 90-day mortality rates (OR 0.71; P = 0.14) or in SICH rates (OR 1.67; P = 0.29).

Conclusions: This meta-analysis reinforces that endovascular management is superior to standard medical management alone for the treatment of AIS due to LVO beyond 6 h of onset in patients with perfusion-imaging selection.

Keywords: DAWN; DEFUSE; ischemic stroke; perfusion; thrombectomy.

Figure 1

Pooled DAWN and DEFUSE-3 modified Rankin Score (mRS) scores. Numbers represent percentages of patients in each outcome group. mRS range is 0–6: 0 indicating no symptoms, 1 no clinical disability, 2 slight disability, 3 moderate disability, 4 moderately severe disability, 5 severe disability, and 6 death. Percentages are rounded to the nearest whole number

Figure 2

Functional independence (mRS 0–2), mortality (mRS 6) at 90 days, and sICH following endovascular or medical management of acute ischemic stroke due to large vessel occlusion. Forest plot of odds ratios for (a) functional independence (modified Rankin score or mRS 0–2) at 90 days, (b) all-cause mortality at 90-day, (c) and symptomatic intracerebral hemorrhage (sICH). Estimated odds ratios and confidence intervals are shown, respectively, by the square box and horizontal line. The combined studies odds ratio and confidence interval are in bold and shown by the horizontal diamond. Heterogeneity tests and effect size are shown

Figure 3

Subgroup analysis of functional independence (mRS 0–2) following endovascular or medical management of acute ischemic stroke due to large vessel occlusion. Forest plot of odds ratios for functional independence (modified Rankin score or mRS 0–2) at 90 days stratified into subgroups: (a) Age, 80 or older and (b) Manner of stroke discovery: Wake-up stroke, unwitnessed, or time-known. Estimated odds ratios and confidence intervals are shown, respectively, by the square box and horizontal line. The combined studies odds ratios and confidence interval are in bold and shown by the horizontal diamond. Heterogeneity tests and effect size are shown