Tenecteplase beyond the 4.5-h window for patients with acute ischemic stroke: An updated meta-analysis of randomized controlled trials

Authors

• Ocílio Ribeiro Gonçalves, Department of Medicine, Federal University of Piauí (UFPI), Teresina, PI, Brazil. ocilio41@gmail.com.
• Luca Scarcia, Diagnostic and Interventional Neuroradiology, Henri Mondor Hospital, Créteil, Île-de-France, France.
• João Gabriel Portela, Department of Medicine, Federal University of Piauí (UFPI), Teresina, PI, Brazil.
• Gabriel Soares Santos, Department of Medicine, Federal University of Piauí (UFPI), Teresina, PI, Brazil.
• Leonardo Januario Cardoso, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
• Anderson Matheus da Silva, Department of Physiology and Pharmacology, Federal University of Pernambuco, Recife, PE, Brazil.
• Altair Pereira de Melo Neto, Department of Medicine, Federal University of Roraima, Boa Vista, RR, Brazil.
• João Victor Sanders, Advocate Health - MidwestFollow
• Luciano Falcão, Department of Medicine, Bahiana School of Health and Public Health, Salvador, BA, Brazil.
• Mariana Letícia de Bastos Maximiano, Deparment of Medicine, Federal Fluminense University, Rio de Janeiro, RJ, Brazil.
• Luis Felipe Porto, Department of Medicine, Federal University of Piauí (UFPI), Teresina, PI, Brazil.
• Frédéric Clarençon, Department of Neuroradiology, Pitié-Salpêtrière Hospital, APHP, Paris, France.
• Thanh Nguyen, Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
• Kelson James Almeida, Department of Medicine, Federal University of Piauí (UFPI), Teresina, PI, Brazil.
• Ahmet Günkan, Division of Vascular and Interventional Radiology, Department of Medical Imaging, University of Arizona, Tucson, Arizona, USA.

Recommended Citation

Gonçalves OR, Scarcia L, Portela JGS, et al. Tenecteplase Beyond the 4.5-h Window for Patients with Acute Ischemic Stroke: An Updated Meta-Analysis of Randomized Controlled Trials. CNS Drugs. Published online June 17, 2026. doi:10.1007/s40263-026-01308-6

Abstract

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 I² 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.

Document Type

Article

PubMed ID

42307864