IV tenecteplase beyond 4.5 hours shows modest benefit but higher bleeding risk in acute ischemic stroke patientsTenecteplase shows modest benefit for late stroke treatment

BACKGROUND: We performed an updated systematic review and meta-analysis to evaluate tenecteplase 0.25 mg/kg in the extended time window. METHODS: MEDLINE was searched via PubMed, Scopus, and Web of Science from inception to February 2026, with trial registries also screened. Eligible trials were RCTs of adults treated beyond 4.5 h from last known well or with wake-up stroke, comparing IV tenecteplase 0.25 mg/kg with placebo or standard care. Primary efficacy outcomes were 90-day mRS 0-1 and mRS 0-2, and primary safety outcomes were symptomatic intracranial hemorrhage and death. RoB 2 and GRADE were used to assess risk of bias and certainty. Risk ratios were pooled using a random effects model. RESULTS: Nine RCTs, including 4,000 participants, met eligibility criteria. Tenecteplase was associated with a modest increase in excellent functional outcome (9 studies, 4000 patients, RR 1.12, 95% CI 1.027 to 1.22, p = 0.01, I: 14.9%) and favorable functional outcome (9 studies, 4000 patients, RR 1.06, 95% CI 1.01 to 1.11, p = 0.0091, I: 10.6%). Tenecteplase showed a significantly higher risk of sICH (9 studies, 4000 patients, RR 1.86, 95% CI 1.065 to 3.24, p = 0.029, I: 21.8%), while no difference was found in death (9 studies, 4000 patients, RR 1.006, 95% CI 0.85 to 1.19, p = 0.95, I: 35.5%). GRADE certainty was high for favorable outcome and death, and moderate for excellent outcome, sICH, reperfusion, and parenchymal hematoma type 2. CONCLUSIONS: In extended window acute ischemic stroke, tenecteplase 0.25 mg/kg improved 90-day functional outcomes and increased reperfusion, but it increased intracranial hemorrhage, including sICH. These findings support careful use in imaging selected patients, with attention to bleeding risk.