Tenecteplase improves functional outcomes and early neurological recovery in late window acute ischemic strokeTenecteplase improves recovery for patients with late stroke treatment

INTRODUCTION: Intravenous thrombolysis (IVT) is the established treatment for acute ischemic stroke (AIS) when administered within 4.5 h of the last known well (LKW) status. However, this narrow therapeutic window limits the number of patients eligible for treatment. In this context, tenecteplase (TNK) is being investigated as an alternative thrombolytic agent in the extended time window. OBJECTIVE: The objective of this study was to evaluate the safety and efficacy of intravenous TNK in patients with AIS treated in the extended time window (beyond 4.5 h from LKW) compared with best medical treatment (BMT) without IVT. METHODS: We conducted a systematic literature review and meta-analysis of patients with AIS presenting beyond 4.5 h from LKW treated with TNK or BMT in randomized controlled trials (RCTs). The safety outcomes included: (1) symptomatic intracranial hemorrhage (sICH), (2) mortality at 90 days, (3) any intracranial hemorrhage (ICH), and (4) parenchymal hemorrhage type 2 (PH2). The efficacy outcomes included: (1) excellent functional outcome (modified Rankin scale [mRS] 0-1) at 90 days, (2) functional independence (mRS 0-2) at 90 days, and (3) early neurological improvement. An analysis based on odds ratios (OR) with 95% confidence intervals (CI) under a random-effects model was used for data pooling. Heterogeneity was assessed using the Q test and its P-value, with the magnitude evaluated by I values. RESULTS: A total of 6 RCTs including 2297 patients were analyzed, with 1152 patients receiving TNK and 1145 receiving BMT. Compared with BMT, TNK administered in the extended time window was associated with significantly higher rates of excellent functional outcomes (mRS 0-1: OR 1.40, 95% CI 1.18-1.67; P < 0.001), functional independence (mRS 0-2: OR 1.27, 95% CI 1.07-1.51; P = 0.006), and early neurological improvement (OR 3.21, 95% CI 1.82-5.66; P < 0.001). TNK was associated with a significant increase in sICH (OR 2.34, 95% CI 1.11-4.95; P = 0.026). No significant differences were observed in 90-day mortality (OR 1.17, 95% CI 0.89-1.55), any ICH (OR 1.61, 95% CI 0.37-6.95), or PH2 (OR 1.81, 95% CI 0.90-3.64). CONCLUSIONS: In patients with AIS treated beyond 4.5 h from symptom onset, intravenous TNK significantly improves functional outcomes and early neurological recovery compared with BMT, without a significant increase in mortality. Although sICH was significantly increased, absolute rates remained low. These findings support the potential role of tenecteplase as an effective thrombolytic option in the extended time window for carefully selected patients. REGISTRATION: PROSPERO identifier no. CRD420251060492.