Endovascular Treatment in Acute Ischemic Stroke Due to Occlusion of Medium or Distal Vessels

Endovascular treatment (EVT) is the standard of care for acute ischemic stroke (AIS) due to large vessel occlusions, but its efficacy and safety in medium or distal vessel occlusions (MDVOs) remain uncertain. This systematic review and meta-analysis evaluated EVT plus best medical treatment (BMT) vs BMT alone in patients with MDVO-AIS. MEDLINE, Scopus, and ClinicalTrials.gov were searched through February 2025 for randomized-controlled clinical trial (RCT) data and observational evidence comparing EVT plus BMT vs BMT alone in adults with MDVO-AIS. The primary efficacy outcome was 3-month excellent functional outcome (modified Rankin Scale mRS-score 0-1), while good functional outcome (mRS score 0-2), reduced disability (mRS shift analysis), and pooled rates of successful recanalization were assessed as secondary outcomes. The primary safety outcome was symptomatic intracranial hemorrhage (sICH), while any ICH, 3-month all-cause mortality, and procedure-related complications were also evaluated. Thirty-eight studies (3 RCTs, 1 post hoc RCT analysis, 1 RCT individual patient data meta-analysis, and 33 observational studies) were included comprising 4,584 EVT-treated patients (mean age 71 years; 46% females) and 5,468 BMT-only patients (mean age 72; 46% females). Patients receiving EVT had similar rates of 3-month excellent functional outcome compared with BMT alone (risk ratio RR 1.02; 95% CI 0.93-1.12; p = 0.676; 30 studies; I2 = 67%). The 2 groups did not differ in good functional outcome (RR 1.00; 95% CI 0.94-1.07; p = 0.933; 36 studies; I2 = 71%) or reduced disability (common odds ratio 0.92; 95% CI 0.80-1.07; p = 0.290; 10 studies; I2 = 20%). The pooled rate of successful recanalization in the EVT arm was 78% (95% CI 75%-82%; 25 studies; I2 = 82%). EVT was associated with higher rates of sICH (RR 1.54; 95% CI 1.18-2.01; p = 0.002; 29 studies; I2 = 24%), any ICH (RR 1.62; 95% CI 1.38-1.92; p < 0.001; 17 studies; I2 = 40%), and 3-month all-cause mortality (RR 1.26; 95% CI 1.05-1.50; p = 0.012; 29 studies; I2 = 27%). The pooled rate of procedure-related complications was 8% (95% CI 5%-12%; 8 studies; I2 = 76%). No significant subgroup differences emerged when stratified for study design or NIH Stroke Scale strata. In this comprehensive synthesis of available evidence, EVT did not improve functional outcomes compared with BMT in MDVO-AIS, while it increased the risk of hemorrhagic complications and mortality. These findings argue against the routine use of EVT for MDVO-AIS. A key limitation is the predominance of observational data, underscoring the need for further RCTs to refine patient selection. The prespecified protocol of the present systematic review and meta-analysis has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO (registration ID: CRD42025651283).