Abstract
Introduction The benefit of endovascular thrombectomy (EVT) beyond 24 hours from last known well (LKW) in acute ischemic stroke (AIS) remains uncertain. While some “slow progressors” may retain salvageable tissue, supporting evidence in this ultra‐late window comes mainly from small observational studies. Methods We systematically searched PubMed, Embase, Scopus, Web of Science, and Cochrane Central up to February 2025 for studies comparing EVT and best medical therapy (BMT) in AIS patients treated >24 hours from LKW. Eligible studies reported functional independence (90‐day 0‐2 mRS), excellent clinical outcome (90‐day 0‐1 mRS), symptomatic intracranial hemorrhage (sICH), or 90‐day mortality. Pooled unadjusted and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random‐effects meta‐analyses. Subgroup analyses were performed by study design, stroke severity, imaging modality, and occlusion territory. Statistical heterogeneity was assessed using the I2 statistic and Cochran's Q test, and the certainty of evidence (CoE) was assessed using the GRADE approach. Results Ten observational studies (3 prospective and 7 retrospective) comprising 1,871 patients (EVT: 866; BMT: 1,009) were included. EVT was associated with significantly higher odds of functional independence (8 studies; adjusted OR [aOR]=4.62; 95% CI: 3.30‐6.47; I2=0%; low CoE) and excellent clinical outcome (2 studies; aOR=5.68; 95% CI: 2.49‐12.97; I2=0%; very‐low CoE). EVT increased the risk of sICH (4 studies; aOR=9.54; 95% CI: 3.78‐21.07; I2=0%; low CoE), but 90‐day mortality did not differ significantly between groups (4 studies; aOR=0.63; 95% CI: 0.30‐1.31; I2=41.2%; very‐low CoE). All subgroup analyses aligned with the main findings. Conclusions Our results revealed that EVT was associated with improved functional outcomes without an increase in 90‐day mortality, despite a higher sICH risk. Given the limited CoE and overall study quality, ongoing randomized trials are essential to confirm these findings and guide patient selection in the ultra‐late time window.