Time-dependent efficacy and safety of endovascular treatment in anterior circulation stroke: A systematic review and meta-analysis.

Acute ischemic stroke of the anterior circulation is a leading cause of mortality and disability. Although endovascular treatment combined with medical therapy (EVMT) has demonstrated substantial efficacy, its risk-benefit profile across different treatment windows remains uncertain. This meta-analysis aimed to evaluate the impact of time from symptom onset on the efficacy and safety of EVMT compared with best medical therapy (BMT) alone. PubMed, Embase, and the Cochrane Library were searched from inception to June 30, 2025. Randomized clinical trials enrolling adults with anterior circulation acute ischemic stroke assigned to EVMT versus BMT were included. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using random-effects models in RevMan version 5.4. The I² statistic was used to measure heterogeneity. Nineteen trials comprising 5,209 patients (2,517 EVMT; 2,692 BMT) were included. EVMT was associated with a reduction in 90-day mortality compared with BMT (OR 0.79; 95% CI 0.67-0.93; P = 0.005), with the strongest effect within ≤ 12 h (OR 0.63; 95% CI 0.46-0.86; P = 0.003). Functional outcomes consistently favored EVMT across all windows (OR 2.44; 95% CI 1.97-3.01; P < 0.0001). EVMT was associated with an overall increased risk of symptomatic intracranial hemorrhage (OR 1.68; 95% CI 1.26-2.23; P = 0.0004), including in the ≤ 12 h, ≤ 24 h, and 6-24 h subgroups, but not within ≤6 h. Treatment effects were significant across time windows, however, with no significant interaction detected. EVMT improves functional outcomes across all evaluated time windows, with a favorable safety profile within 6 h from symptom onset and an |increased hemorrhagic risk with delayed treatment, without evidence of significant effect modification by time.