Efficacy and safety of tenecteplase administration in extended time window for acute ischemic stroke: An updated meta-analysis of randomized controlled trials

Background: Data regarding the efficacy and safety of tenecteplase (TNK) in patients with acute ischemic stroke (AIS) who present outside the standard treatment window are limited. This study aims to evaluate the role of TNK at a dose of 0.25 mg/kg, in treating AIS patients in an extended time window. Methods: Searches were performed up to February 15, 2025 in PubMed, Embase, and Cochrane Library to include randomized-controlled trials (RCTs) comparing TNK (0.25 mg/kg) to no thrombolysis in AIS patients presenting after 4.5 hours of symptom onset or wake-up AIS. The primary efficacy outcomes included a 3-month excellent functional outcome (mRS <= 1), and a good functional outcome (mRS <= 2). Secondary safety outcomes assessed included symptomatic intracranial hemorrhage (sICH), any ICH, and 3-month all-cause death. A random-effects model was used to calculate summary estimates. Results: 6 RCTs were included (n = 1,955 patients) in the meta-analysis. The pooled analysis demonstrated a significantly improved excellent functional outcome on 90 days (OR = 1.35, 95 % CI: 1.12 to 1.64) with TNK administration compared to control. No statistically significant association was observed for the two groups regarding good functional outcome (OR = 1.16, 95 % CI: 0.94 to 1.44), all-cause death (OR = 1.11, 95 % CI: 0.82 to 1.49), sICH (OR = 1.79, 95 % CI: 0.94 to 3.39), and any ICH (OR = 1.21, 95 % CI: 0.96 to 1.53). Conclusion: TNK administration in an extended time window for AIS patients leads to favorable neurological outcomes with a good safety profile.