Tenecteplase Matches Alteplase in Safety and Effectiveness for Acute Ischemic Stroke, Study Finds

Acute ischemic stroke, which occurs due to a blockage in cerebral blood flow, requires prompt intervention with thrombolytic agents to restore circulation and minimize neurological damage. While alteplase has been the standard treatment for years, the researchers note that tenecteplase is gaining attention as a potential alternative due to its ease of administration and pharmacological advantages. However, limited data comparing their clinical effectiveness in routine clinical practice are available.

To fill this knowledge gap, Justin F. Rousseau, Peter O’Donnell Jr Brain Institute, University of Texas Southwestern Medical Center, Dallas, and colleagues aimed to evaluate the short-term safety and effectiveness of intravenous tenecteplase versus alteplase in patients with ischemic stroke. 

For this purpose, the researchers conducted a comparative effectiveness study using data from the Get With The Guidelines–Stroke registry, collected between July 2020 and June 2022. They analyzed consecutive ischemic stroke patients treated with tenecteplase or alteplase within 4.5 hours of symptom onset.

The primary outcome was functional independence at discharge, while secondary outcomes included disability-free status, discharge home, and independent ambulation. Safety outcomes assessed symptomatic intracranial hemorrhage and in-hospital mortality or hospice discharge. Using generalized linear mixed models, they adjusted for multiple factors and calculated adjusted odds ratios with 95% confidence intervals to compare both treatments.

Key Findings:

• The study included 79,550 stroke patients who received intravenous thrombolysis, with an average age of 68.6 years. Of these, 48.5% were female, and the median NIHSS stroke severity score was 7.
• Tenecteplase was given to 11.9% (9,465 patients) with an average age of 69.6 years, while alteplase was used in 88.1% (70,085 patients) with an average age of 68.5 years.
• After adjusting for various factors, there were no major differences between tenecteplase and alteplase in terms of functional independence at discharge, symptomatic intracranial hemorrhage, or in-hospital mortality/hospice discharge.
• However, tenecteplase showed benefits among patients eligible for but not undergoing endovascular thrombectomy, including a higher likelihood of discharge home, lower in-hospital mortality, and reduced combined in-hospital or hospice discharge.

The large, nationwide study using real-world clinical data found that tenecteplase offers similar short-term safety and effectiveness as alteplase for acute ischemic stroke.

"The findings support tenecteplase as a viable alternative, with practical benefits in preparation and administration. As its use expands across different stroke centers and patient groups, further research may reveal subtle yet clinically significant differences in outcomes between the two treatments," the authors concluded.

Reference:

Rousseau JF, Weber JM, Alhanti B, et al. Short-Term Safety and Effectiveness for Tenecteplase and Alteplase in Acute Ischemic Stroke. JAMA Netw Open. 2025;8(3):e250548. doi:10.1001/jamanetworkopen.2025.0548