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Comparative Study
. 2025 Mar 3;8(3):e250548.
doi: 10.1001/jamanetworkopen.2025.0548.

Short-Term Safety and Effectiveness for Tenecteplase and Alteplase in Acute Ischemic Stroke

Justin F Rousseau  1   2 , Jeremy M Weber  3 , Brooke Alhanti  3 , Jeffrey L Saver  4 , Steven R Messé  5 , Lee H Schwamm  6   7 , Gregg C Fonarow  8   9 , Kevin N Sheth  6   10 , Eric E Smith  11 , Michael T Mullen  12 , Gisele Sampaio Silva  13 , Brian Mac Grory  3   14 , Ying Xian  1   2 , Steven J Warach  15   16
Affiliations
Comparative Study

Short-Term Safety and Effectiveness for Tenecteplase and Alteplase in Acute Ischemic Stroke

Justin F Rousseau et al. JAMA Netw Open. .

Erratum in

  • Error in Figure 2.
    [No authors listed] [No authors listed] JAMA Netw Open. 2025 Jul 1;8(7):e2524999. doi: 10.1001/jamanetworkopen.2025.24999. JAMA Netw Open. 2025. PMID: 40627359 Free PMC article. No abstract available.

Abstract

Importance: Tenecteplase is an alternative to alteplase for emergency treatment of acute ischemic stroke. However, limited data are available comparing their clinical effectiveness in routine clinical practice.

Objective: To compare short-term effectiveness and safety outcomes for patients with ischemic stroke treated with intravenous tenecteplase vs alteplase.

Design, setting, and participants: This comparative effectiveness study used data prospectively collected from July 1, 2020, through June 30, 2022, from the Get With The Guidelines-Stroke registry.

Exposure: Consecutive patients with ischemic stroke treated with either tenecteplase or alteplase within 4.5 hours from last known well time were included.

Main outcomes and measures: The primary end point was functional independence on discharge (modified Rankin Scale [mRS] score, 0-2). Secondary effectiveness end points included disability free at discharge (mRS score, 0-1), discharge home, and independent ambulation at discharge. Safety end points included symptomatic intracranial hemorrhage (sICH) within 36 hours and combined in-hospital mortality or hospice discharge. Generalized linear mixed models were fit to evaluate associations between exposure to tenecteplase (vs alteplase) and end points after adjustment for demographic, clinical, and hospital-level variables. Adjusted odds ratios (AORs) with 95% CIs were computed.

Results: Among 79 550 patients treated with intravenous thrombolysis, the mean (SD) age was 68.6 (14.8) years, 38 596 (48.5%) were female, and the median National Institutes of Health Stroke Scale (NIHSS) score was 7 (IQR, 4-13). Of these patients, 9465 (11.9%) received tenecteplase (mean [SD] age, 69.6 [14.7] years; median NIHSS score, 7 [IQR, 4-14]; 4504 [47.6%] female) and 70 085 (88.1%) received alteplase (mean [SD] age, 68.5 [14.8] years; median NIHSS score, 7 [IQR, 4-13]; 34 092 [48.6%] female). After adjustment for covariates, no significant differences were found between tenecteplase and alteplase in effectiveness or safety outcomes for the overall cohort, including functional independence at discharge (AOR, 1.00; 95% CI, 0.93-1.07), sICH (AOR, 0.96; 95% CI, 0.83-1.11), and in-hospital mortality or hospice discharge (AOR, 0.98; 95% CI, 0.89-1.07), but significant improvement was found in discharge home (AOR, 1.26; 95% CI, 1.03-1.53), in-hospital mortality (AOR, 0.63; 95% CI, 0.47-0.85), and composite in-hospital mortality or hospice discharge (AOR, 0.78; 95% CI, 0.62-0.97) among those who were eligible for but did not undergo endovascular thrombectomy.

Conclusions and relevance: This large, nationwide comparative effectiveness study using data from routine clinical practice demonstrated similar effectiveness and safety outcomes with tenecteplase compared with alteplase in patients with acute ischemic stroke. This study supports tenecteplase as a reasonable alternative to alteplase.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Rousseau reported receiving grants from the National Library of Medicine, National Institute of General Medical Sciences, National Institute on Aging, National Institute of Mental Health, National Center for Advancing Translational Sciences, National Institute of Allergy and Infectious Diseases, Texas Child Mental Health Care Consortium, Michael & Susan Dell Foundation, Texas Alzheimer’s Research and Care Consortium, and Health Care Cost Institute; a loan repayment award from the National Institutes of Health and National Center for Advancing Translational Sciences; and a research contract from the Austin Public Health University outside the submitted work. Dr Saver reported receiving personal fees from Roche, Genentech, and Medtronic outside the submitted work. Dr Messé reported receiving grants from the National Institutes of Health and personal fees from WL Gore, Graviton, Novo Nordisk, and Conformal outside the submitted work and is a cofounder of Neuralert Technologies. Dr Schwamm reported receiving personal fees from Genentech and personal fees and grants from Medtronic outside the submitted work. Dr Sheth reported receiving grants from the National Institutes of Health, Hyperfine, Genentech, and American Heart Association during the conduct of the study and serving on the advisory boards for Bexorg, Astrocyte, and BrainQ outside the submitted work; in addition, Dr Sheth had a patent for Alva issued. Dr Silva reported receiving grants from the Boehringer Ingelheim Resilient Extend IV trial and personal fees from Boehringer Ingelheim and AstraZeneca outside the submitted work. Dr Mac Grory reported receiving grants from the National Institutes of Health during the conduct of the study. Dr Xian reported receiving grants from Genentech and personal fees from Boehringer Ingelheim during the conduct of the study and receiving grants from the National Institute on Aging outside the submitted work. Dr Warach reported receiving personal fees from Genentech outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flow Diagram of Study Population With Inclusion and Exclusion Criteria
EVT indicates endovascular thrombectomy; GWTG-Stroke, Get With The Guidelines–Stroke; IV, intravenous; LVO, large vessel occlusion; NIHSS, National Institutes of Health Stroke Scale.
Figure 2.
Figure 2.. Adjusted Odds Ratios of Tenecteplase vs Alteplase
AOR indicates adjusted odds ratio; EVT, endovascular thrombectomy; LVO, large vessel occlusion; sICH, symptomatic intracranial hemorrhage.
See this image and copyright information in PMC

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