J Stroke.  2025 May;27(2):184-194. 10.5853/jos.2024.05715.

Tenecteplase Beyond 4.5 Hours in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

• Aladawi M
• Abuawwad MT
• Taha MJJ
• Kozaa YA
• Alrubasy WA
• Hamad A
• Alhnidi FA
• Elfil M
• Najdawi Z
• Peng X
• Hataway F
• Bakradze E
• Lyerly MJ

• KMID: 2568224
• DOI: http://doi.org/10.5853/jos.2024.05715

Abstract

Background and Purpose
Acute ischemic stroke (AIS) is a leading cause of disability worldwide. While intravenous thrombolysis is recommended within 4.5 hours of last known well (LKW) time, many patients present beyond this window.
Methods
We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating tenecteplase (TNK) administration in AIS patients within 4.5 to 24 hours of LKW. The primary outcomes assessed functional independence and ordinal modified Rankin Scale (mRS) shift at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and mortality at 90 days.
Results
Three RCTs were included, comprising 1,054 patients (532 TNK and 522 standard medical therapy) with a mean age of 69 years, 59% males, and median baseline National Institutes of Health Stroke Scale score of 10.5. TNK treatment was associated with mRS 0–2 at 90 days (odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.04–1.70, P=0.023), indicating a 33% higher likelihood of achieving functional independence. However, the ordinal mRS shift showed no significant difference (standardized mean difference: 0.01, 95% CI: -0.37–0.39, P=0.09). Safety outcomes indicated no difference in the rates of sICH (OR: 2.07, 95% CI: 0.86–5.00, P=0.1), and no difference in 90-day mortality (OR: 1.08, 95% CI: 0.76–1.53, P=0.67).
Conclusion
This meta-analysis suggests TNK might be safe and effective for selected AIS patients in the 4.5- to 24-hour time window, offering improved functional outcomes without a significant increase in hemorrhagic complications.

Keyword

Tenecteplase; Intravenous thrombolysis; Acute ischemic stroke; Extended treatment window