Tenecteplase for the treatment of acute ischemic stroke in the extended time window: a systematic review and meta-analysis

Lina Palaiodimou; Aristeidis H Katsanos; Guillaume Turc; Michele Romoli; Aikaterini Theodorou; Robin Lemmens; Simona Sacco; Georgios Velonakis; Charalambos Vlachopoulos; Georgios Tsivgoulis

doi:10.1177/17562864231221324

Tenecteplase for the treatment of acute ischemic stroke in the extended time window: a systematic review and meta-analysis

Ther Adv Neurol Disord. 2024 Jan 6:17:17562864231221324. doi: 10.1177/17562864231221324. eCollection 2024.

Authors

Affiliations

¹ Second Department of Neurology, 'Attikon' University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
² Department of Medicine (Neurology), McMaster University/Population Health Research Institute, Hamilton, ON, Canada.
³ Department of Neurology, GHU Paris Psychiatrie et Neurosciences, Paris, France.
⁴ Université Paris Cité, Paris, France.
⁵ INSERM U1266, Paris, France.
⁶ FHU NeuroVasc, Paris, France.
⁷ Neurology and Stroke Unit, Department of Neuroscience, Bufalini Hospital, Cesena, Italy.
⁸ Department of Neurology, University Hospitals Leuven, Leuven, Belgium.
⁹ Department of Neurosciences, Division of Experimental Neurology, KU Leuven - University of Leuven, Leuven, Belgium.
¹⁰ Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
¹¹ Research Unit of Radiology, Second Department of Radiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
¹² First Department of Cardiology, Hippokration Hospital, University of Athens, Athens, Greece.
¹³ Second Department of Neurology, 'Attikon' University Hospital, School of Medicine, National and Kapodistrian University of Athens, Rimini 1, Chaidari, Athens 12462, Greece Department of Neurology, University of Tennessee Health Science Center, Memphis, TN, USA.

Abstract

Background: Outcome data regarding the administration of tenecteplase (TNK) to acute ischemic stroke (AIS) patients presenting in the extended time window are limited.

Objectives: We aimed to assess the current evidence regarding the efficacy and safety of TNK at a dose of 0.25 mg/kg for AIS treatment in the extended time window.

Design: A systematic review and meta-analysis was conducted including all available randomized-controlled clinical trials (RCTs) that compared TNK 0.25 mg/kg versus no thrombolysis in AIS patients presenting in the extended time window (>4.5 h after last-seen-well or witnessed onset).

Data sources and methods: Eligible studies were identified by searching Medline, Scopus, and international conference abstracts. The predefined efficacy outcomes of interest were 3-month excellent functional outcome [defined as the modified Rankin Scale (mRS) score ⩽1; primary outcome], 3-month good functional outcome (mRS ⩽ 2), 3-month reduced disability (⩾1-point reduction across all mRS scores). We determined symptomatic intracranial hemorrhage (sICH), any ICH and 3-month mortality as safety endpoints. A random-effects model was used to calculate risk ratios (RRs) and common odds ratios (cORs) with corresponding 95% confidence intervals (CIs).

Results: Three RCTs were included comprising 556 patients treated with TNK versus 560 controls. TNK 0.25 mg/kg was associated with a higher likelihood of 3-month excellent functional outcome compared to controls (RR = 1.17; 95% CI = 1.01-1.36; I² = 0%), whereas there was no difference regarding good functional outcome (RR = 1.05; 95% CI = 0.94-1.17; I² = 0%) and reduced disability (adjusted cOR = 1.14; 95% CI = 0.92-1.40; I² = 0%) at 3 months. The risks of sICH (RR = 1.67; 95% CI = 0.70-4.00; I² = 0%), any ICH (RR = 1.08; 95% CI = 0.90-1.29; I² = 0%) and 3-month mortality (RR = 1.10; 95% CI = 0.81-1.49; I² = 0%) were similar between the groups.

Conclusion: Based on data from three RCTs showing increased efficacy and a favorable safety profile of TNK in the treatment of AIS in the extended time window, continuing efforts of ongoing RCTs in the field are clearly supported.

Trial registration: PROSPERO registration ID: CRD42023448707.

Keywords: acute ischemic stroke; extended time window; intravenous thrombolysis; meta-analysis; randomized-controlled clinical trials; tenecteplase.