Abstract Body (Do not enter title and authors here): INTRODUCTION
Distal medium vessel occlusions (DMVO), which represent about 25-40% of acute ischemic stroke cases, are a major cause of morbidity and mortality worldwide. Intravenous thrombolysis (as part of best medical treatment (BMT)) remains the primary treatment for these patients; however, there is increasing evidence of the use of endovascular treatments (EVT) (such as mechanical thrombectomy) along with BMT in these patients. Yet, the risk-benefit ratio of EVTs in patients with DMVOs is still uncertain.
OBJECTIVE
To compare the efficacy and safety of combination therapy of EVT+BMT to BMT alone in acute ischemic stroke patients with DMVO.
METHODOLOGY
A systematic search of PubMed, Embase, Scopus, Cochrane Library, Google Scholar, and ClinicalTrials.gov identified RCTs and observational studies comparing combination therapy of EVT+BMT with BMT (inception–May 2025). The study was registered with PROSPERO (ID: CRD420251069717). Outcomes included functional assessment with a modified Rankin scale (mRS) and safety of treatments measured as the incidence of intracranial hemorrhage (ICH) and mortality within 90 days. Data were analyzed using RevMan 4.2.1, with pooled RRs (95% CIs) via Mantel-Haenszel methods. Random/fixed-effects models were applied based on heterogeneity (I2) with statistical significance: p <0.05.

RESULTS
Meta-analysis of 6 studies involving 1688 patients showed a non-significant trend towards improved functional outcomes in combination therapy. The EVT+BMT group showed a slightly higher proportion of excellent functional outcomes (mRS 0-1 at 90 days) (372/916 vs 402/910; RR 0.91; 95% CI, 0.82–1.01; p = 0.09) and good functional outcomes (mRS 0-2 at 90 days) (420/720 vs 450/715; RR 0.92; 95% CI, 0.85–1.00; p = 0.06). Safety outcomes significantly favored the BMT group due to the higher incidence of ICH in the combination therapy group occurring in 67/993 vs. 41/985 participants (RR 1.62; 95% CI, 1.12–2.35; p = 0.01) and nearly double the rate of as ICH (161/619 vs. 80/620; RR 2.02; 95% CI, 1.58–2.57; p < 0.00001). 90-day mortality did not differ significantly but numerically favored the BMT group (131/910 vs. 104/910; RR 1.22; 95% CI, 0.96–1.55; p = 0.10).
CONCLUSION
In acute ischemic stroke due to DMVO, EVT plus BMT may improve functional outcomes over BMT alone; however, the higher rates of symptomatic and asymptomatic ICH raise concerns about bleeding risk, warranting cautious patient selection until validated by RCTs.