Tenecteplase versus Standard Care for Acute Ischemic Stroke in the 4.5–24 Hour Window: An Updated Systematic Review and Meta-Analysis

Acute ischemic stroke (AIS) is a leading cause of disability and mortality worldwide. Intravenous thrombolysis with alteplase has been standard within 4.5 hours of symptom onset for decades. However, many patients present beyond this time window, often with salvageable penumbra identified on advanced imaging . Tenecteplase, a genetically modified variant of tissue plasminogen activator with longer half-life and higher fibrin specificity, has emerged as a promising alternative for late-window treatment. Recent randomized controlled trials (RCTs) have investigated tenecteplase in the 4.5–24 hour window, with varying results depending on patient population (LVO vs. non-LVO) and whether endovascular thrombectomy (EVT) was performed. The OPTION trial (2026) demonstrated benefit in non-LVO patients , while TRACE-III (2024) showed efficacy in LVO patients without EVT access. In contrast, bridging therapy trials (TIMELESS, CHABLIS-T II, ATTENTION LATE, TNK-PLUS) showed no benefit when tenecteplase was administered prior to planned EVT . No existing systematic review has performed a stratified meta-analysis comparing sole therapy (tenecteplase without planned EVT) versus bridging therapy (tenecteplase prior to EVT). This review aims to fill that evidence gap.