Tenecteplase for anterior-circulation vessel occlusion at 4.5-24 hours across reperfusion paradigms: A meta-analysis

IntroductionThe role of intravenous tenecteplase (TNK) in patients with acute ischemic stroke presenting 4.5-24 hours after last known well remains uncertain.MethodsWe performed a systematic review and frequentist and Bayesian meta-analysis of Randomized Controlled Trials (RCTs) comparing TNK-containing with trial-specific non-TNK strategies in imaging-selected patients with anterior-circulation large- or medium-vessel occlusion treated 4.5-24 hours after last known well. Trials represented heterogeneous reperfusion paradigms. The primary efficacy outcome was mRS 0-1 at 90 days; other functional, neurological, reperfusion, and recanalization outcomes were secondary or exploratory, and hemorrhagic events were assessed separately as safety outcomes.ResultsFour multicenter RCTs comprising 1,589 patients were included. Frequentist analysis showed no significant difference in the primary outcome, mRS 0-1 at 90 days (OR 1.29, 95% CI 0.99-1.67), or in secondary functional outcomes and mortality. Symptomatic intracranial hemorrhage (OR 1.79, 95% CI 0.88-3.60) and parenchymal hematoma (OR 2.02, 95% CI 0.60-6.74) were numerically more frequent with TNK. No significant interaction was observed according to reperfusion strategy (P-interaction >0.36), although subgroup analyses were exploratory and underpowered. Bayesian analyses yielded estimates favoring TNK for excellent functional outcome (OR 1.29, 95% CrI 1.10-1.51) but also suggested increased risks of symptomatic intracranial hemorrhage (OR 1.79, 95% CrI 1.15-2.76) and parenchymal hematoma (OR 2.02, 95% CrI 1.14-3.47); these findings should be interpreted cautiously given their dependence on Bayesian model assumptions.ConclusionAcross heterogeneous reperfusion paradigms, TNK-containing strategies showed no consistent functional benefit, while hemorrhagic outcomes raised a potential safety signal. Pooled estimates should not be interpreted as a uniform treatment effect.