Supplementary Material for: Intra-arterial Fibrinolysis Post Successful Endovascular Reperfusion for Acute Ischemic Stroke: A Systematic Review and Meta-analysis

Background and Purpose: Acute ischemic stroke (AIS) due to large vessel occlusion (LVO) remains a leading cause of disability and mortality. While endovascular thrombectomy (EVT) achieves high macrovascular reperfusion rates, residual microvascular obstruction may possibly contribute to poor outcome. This systematic review and meta-analysis assess the efficacy and safety of intra-arterial fibrinolysis (IAF) administered post-successful EVT.
Methods: Following a PROSPERO-registered protocol (CRD420250642689), we systematically analyzed four randomized controlled trials (RCTs, n=1,392) and presented one observational study (n=81) separately comparing EVT alone versus EVT plus IAF in AIS-LVO patients achieving successful reperfusion (mTICI ≥ 2b50). Primary outcomes included 90-day functional independence (mRS 0-1, 0-2), while secondary outcomes evaluated mortality and hemorrhagic complications.
Results: IAF mildly improved the rate of excellent functional outcomes (mRS 0-1: RR 1.17, 95% CI 1.03-1.32, p<0.05) but did not enhance overall functional independence (mRS 0-2: RR 1.03, 95% CI 0.94-1.13, p=0.56). No significant differences were observed in 90-day mortality (RR 0.93, 95% CI 0.75-1.16, p=0.54) or symptomatic intracranial hemorrhage (RR 1.28, 95% CI 0.79-2.06, p=0.32). Any intracranial hemorrhage incidence was higher but no significant difference (RR 1.89, 95% CI 0.73-4.90, p=0.19).
Conclusion: Adjunctive IAF following successful EVT may enhance the likelihood of excellent functional recovery without increasing mortality or major hemorrhagic risks. However, it still has some limitations such as specific obstruction positions, IAF types, IAF dosage etc. Further high-quality RCTs are warranted to refine patient selection and optimize IAF protocols.