Nine RCTs (n=7,903; mean age 67.7 years; 58.9% male) were included. Compared to controls, neuroprotectants were associated with higher odds of achieving favorable functional outcomes (mRS ≤1) at 90 days (OR = 1.22; 95% CI: 1.04–1.43) but with higher rates of infusion-related (OR 1.48; 95% CI 1.19–1.86) and treatment-related (OR 1.34; 95% CI 1.12–1.60) adverse events. Although severe AE leading to withdrawal were less frequent (OR 0.72; 95% CI 0.56–0.91) in the treatment group. A small and statistically insignificant improvement was observed in both NIHSS at 14 days (MD –0.21; 95% CI –0.50 to 0.08) and BI. Cognitive outcome by Montreal Cognitive Assessment Score (MoCA) and mortality were not significantly different.

Pooled clinical data in AIS patients receiving endovascular treatment reveal that use of neuroprotective agents has a modest functional benefit but a consistent safety signal for increased treatment-related adverse events. These findings challenge the role of currently available neuroprotectants in AIS and underscore the need for future trials targeting patient subgroups, optimizing dosing strategies, and prioritizing long-term functional recovery.