Abstract WP002: Safety and Efficacy of Intra-Arterial Thrombolysis After Endovascular Thrombectomy for Large-Vessel Occlusion: A Dose-Wise Network Meta-analysis of Randomized Trials

Background: The benefit of adjunct intra-arterial (IA) thrombolysis post endovascular thrombectomy (EVT) for acute ischemic stroke remains unclear. We aim to compare the efficacy and safety of IA thrombolytic agents used in post-EVT, with particular attention to dose variation. Methods: We included randomized controlled trials of adult patients with large-vessel occlusion stroke that compared EVT alone with EVT plus IA thrombolysis. PubMed, Scopus, Embase, and the Cochrane Library were searched for relevant studies (up to 10/08/2025). The primary outcome was excellent functional recovery (modified Rankin Scale [mRS] 0–1 at 90 days). Safety outcomes were intracerebral hemorrhage (ICH) and 90-day mortality. Odds ratios were calculated using a random-effects frequentist network meta-analysis with the DerSimonian Laird estimator. Language refinement was assisted by ChatGPT (OpenAI, GPT-5). Results: Eight RCTs (n=2,148) informed functional independence (mRS 0–1 at 90 days). Compared with EVT alone, EVT plus intra-arterial alteplase 0.225 mg/kg significantly improved functional independence (OR 1.98, 95% CI 1.35–2.92, p=0.0005), and EVT plus Tenecteplase 0.125 mg/kg also showed benefit (OR 1.90, 95% CI 1.12–3.23, p=0.017). Other regimens did not achieve statistical significance. For safety, seven RCTs (n=1,844) demonstrated no increased risk of intracerebral hemorrhage with IA agents (e.g., alteplase OR 0.27, 95% CI 0.03–2.15; urokinase OR 1.00, 95% CI 0.43–2.35), while IA tenecteplase 0.0625 mg/kg showed a nonsignificant trend toward higher ICH (OR 1.76, 95% CI 0.94–3.28; p=0.076; I^2=0%). Six RCTs (n=1,804) demonstrated no significant mortality difference across IA thrombolysis regimens compared with EVT alone. Heterogeneity and inconsistency were low across analyses (I^2 = 0%). Conclusions: Adjunctive IA Alteplase and Tenecteplase after EVT improved functional recovery with no increase in ICH or mortality, and higher dose Tenecteplase appeared to yield a superior outcome compared to lower dose, underscoring the need for larger trials to refine optimal regimens. Keywords: Endovascular thrombectomy, Intra-arterial thrombolysis, Acute ischemic stroke