Abstract Background and aims Recent randomized trials suggest that endovascular therapy (EVT) may not provide a significant benefit to patients with medium vessel occlusions (MeVOs). We aimed to develop a model to predict 90-day functional outcomes in patients with MeVOs to better recognize those at high-risk. Methods We conducted a retrospective cohort study using a prospective dual-center database of consecutive patients with primary MeVOs (distal or non-dominant M2, M3, A2-A3, P1-P2) who underwent EVT or medical management (MM) between January 2022 and May 2025. Predictors were identified using the Least Absolute Shrinkage and Selection Operator (LASSO) regression. Poor functional outcome was defined as mRS 3-6. Interaction plots were examined to identify clinically meaningful cutpoints. Results A total of 296 patients (median age: 77, IQR: 68-84.2; 56.3% males) were included. Among them, 77.7% (N=230) underwent EVT, and 22.3% (N=66) received MM. The final model selected age, admission NIHSS, Tmax10s, CBF 30%, history of hypertension, and use of IV thrombolysis as predictors of poor functional outcome at 90-days. In this model, increasing age was associated with poor functional outcome (aOR: 1.05 95%CI: 1.02-1.08; p=0.001). Furthermore, we identified a significant interaction between EVT and age (p=0.022; Figure 1). When stratifying the cohort by age, we observed that EVT has a positive effect only in younger patients (69 years) (Figure 2). Conclusions Our study suggests a clear differential benefit of EVT in patients with MeVOs who are younger than 69 years.This finding is crucial for stratifying higher-risk patients and informing selection criteria for future MEVOs studies. Conflict of interest Santiago Ortega-Gutierrez received grants from NIH-NINDS (R01NS127114, R01NS138765, R03NS126804), PCORI, Stryker, Medtronic, and Methinks. Marc Ribo is the Chief Medical Office of Methinks and has equity interests. Anderson Brito and the rest of the team have nothing to disclose. Figure 1 - belongs to Results Figure 2 - belongs to Results
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