Bridging therapy versus direct mechanical thrombectomy in acute ischemic stroke: an updated meta-analysis of real-world evidence.

While randomized controlled trials (RCTs) have compared bridging therapy (BT: IV thrombolysis prior to mechanical thrombectomy) with direct mechanical thrombectomy (dMT) in patients with acute ischemic stroke (AIS), their findings are inconsistent and may not fully represent real-world clinical practice. This study provides an updated synthesis of real-world observational data comparing the safety and efficacy of BT versus dMT in AIS due to large vessel occlusion (LVO). A systematic literature search was conducted across four major databases. Non-randomized studies comparing BT with dMT in AIS patients were included. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models for key clinical outcomes. Risk of bias was assessed using the Newcastle-Ottawa Scale, and publication bias was evaluated through funnel plot symmetry and Egger's test. Thirty-one observational studies involving 93,297 patients (41,393 BT; 47,960 dMT) were included. BT was associated with significantly higher odds of excellent [modified Rankin Scale (mRS) 0-1; OR = 1.51, 95%CI: 1.30-1.77] and favorable (mRS 0-2; OR = 1.44, 95% CI: 1.29-1.61) recovery at 90 days, greater rates of successful reperfusion (TICI 2b/3; OR = 1.23, 95%CI: 1.09-1.39), and lower 90-day mortality (OR = 0.61, 95% CI: 0.52-0.71) compared with dMT. No significant differences were found in rates of symptomatic intracranial hemorrhage. Sensitivity analyses and publication bias assessments supported the robustness of these findings. Meta-regression identified baseline ASPECTS, NIHSS score, and several workflow intervals as significant predictors of outcome variability. These results support BT's continued relevance in routine AIS care. Systematic review registration: PROSPERO no: CRD420251119894.