Background: Recent studies highlight the benefits of endovascular thrombectomy (EVT) combined with standard medical treatment (SMT) for acute ischemic stroke (AIS) patients with large infarcts compared to SMT alone. Objective: This study evaluates the efficacy, bleeding risk, and mortality of EVT versus SMT in AIS patients with Alberta Stroke Program Early CT Score (ASPECTS) ≤5. Methods: A systematic review of MEDLINE, Embase, and Cochrane databases was conducted on June 6, 2024, to identify randomized controlled trials (RCTs) comparing EVT plus SMT with SMT alone in AIS patients with ASPECTS ≤5. Primary outcomes included successful reperfusion, modified Rankin scale (mRS) scores of 0–2 and 0–3, and neurological improvement. Secondary outcomes assessed all-cause mortality, intracranial hemorrhage (ICH), and EQ-5D-5L Utility Index. Statistical analyses applied the Mantel–Haenszel method with 95% confidence intervals (CIs), with heterogeneity evaluated via I2 statistics. Results: Six RCTs involving 1887 patients (944 receiving EVT) were included. EVT significantly increased the incidence of mRS 0–2 (RR 2.50; 95% CI 1.89 to 3.30; p < .001; I2 = 8%) and mRS 0–3 (RR 1.92; 95% CI 1.50 to 2.46; p < .001; I2 = 62%). However, EVT was associated with a higher risk of ICH (RR 1.73; 95% CI 1.11 to 2.69; p = .016; I2 = 0%) and did not reduce mortality compared to SMT (RR 0.86; 95% CI 0.72 to 1.02; p = .082; I2 = 47%). Conclusion: EVT improves functional outcomes in AIS patients with moderate-to-low ASPECTS but increases the risk of ICH without reducing mortality.
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