Background and objectives: There is uncertainty about whether patients with an anterior circulation large vessel occlusion (LVO) and a low NIH Stroke Scale (NIHSS) score (≤5) benefit from endovascular therapy (EVT) in the late time window (6-24 hours). We compared the clinical outcomes of these patients receiving EVT with those receiving medical management (MM).

Methods: The CT for Late Endovascular Reperfusion multinational cohort study was conducted at 66 sites across 10 countries from January 2014 to May 2022. This subanalysis included consecutive patients with late-window stroke due to an anterior circulation LVO, defined as occlusion of the internal carotid artery or proximal middle cerebral artery (M1/M2 segments), and a baseline NIHSS score ≤5 who received EVT or MM alone. The primary end point was a 90-day ordinal shift in the modified Rankin Scale (mRS) score. Secondary outcomes were 90-day excellent outcome (defined as mRS scores 0-1 or return to baseline mRS score in patients with a prestroke mRS score >1) and favorable outcome (defined as mRS scores 0-2 or return to baseline mRS score in patients with prestroke mRS score >2). Safety outcomes were symptomatic intracranial hemorrhage and 90-day mortality. We used ordinal and binary logistic regression models to test for outcome differences.

Results: Among 5,098 patients, 318 patients were included (median [interquartile range] age 67 [56-76] years; 149 [46.9%] were female; baseline NIHSS score was 4 [2-5]). A total of 202 patients (63.5%) received EVT and 116 MM (36.5%). There was no difference in favorable 90-day ordinal mRS score shift (adjusted common odds ratio [OR] 0.77, 95% CI 0.45-1.32), excellent outcome (adjusted OR 0.86, 95% CI 0.49-1.50), or favorable outcome (adjusted OR 0.72, 95% CI 0.35-1.50) in the EVT group compared with MM. Symptomatic intracranial hemorrhage risk (adjusted OR 3.40, 95% CI 0.84-13.73) and mortality at 90 days (adjusted OR 2.44, 95% CI 0.60-10.02) were not statistically different between treatment groups.

Discussion: In patients with an anterior LVO and low NIHSS score in the 6-24-hour time window, there was no statistical difference in disability outcomes or intracranial bleeding risk between patients treated with EVT compared with MM. The retrospective and observational design limits our findings. Ongoing randomized controlled trials will provide further insight.

Classification of evidence: This study provides Class III evidence that in adult patients with anterior circulation LVO and low NIHSS score (≤5) presenting in the late time window (6-24 hours), EVT does not improve clinical outcome vs MM.

Trial registration: This study was registered at clinicaltrials.gov under NCT04096248.