Safety, Functional Disability, Healthcare Utilization, and Quality-of-Life Outcomes in Elderly Receiving Alteplase and Tenecteplase: A Secondary Analysis From the AcT Trial

Nishita Singh^{1

2}, Fouzi Bala^{3

4}, Ayoola Ademola^{1

5}, Mohammed Almekhlafi^{1

3

5}, Shelagh B Coutts^{1

3

5}, Yan Deschaintre⁶, Houman Khosravani⁷, Brian H Buck⁸, Ramana Appireddy⁹, Francois Moreau¹⁰, Gord Gubitz¹¹, Aleksander Tkach¹², Luciana Catanese¹³, Dar Dowlatshahi¹⁴, George Medvedev¹⁵, Jennifer Mandzia¹⁶, Aleksandra Pikula¹⁷, Jai Jai Shankar¹⁸, Alexandre Y Poppe⁶, Heather Williams¹⁹, Thalia S Field¹⁵, Alejandro Manosalva²⁰, Muzaffar Siddiqui²¹, Atif Zafar²², Oje Imoukhoude²³, Gary Hunter²⁴, Michel Shamy¹⁴, Andrew Demchuk¹, Richard H Swartz⁷, Michael D Hill^{1

3

5}, Tolulope T Sajobi^{1

5}, Bijoy K Menon^{1

3

5}, Aravind Ganesh^{1

5}

Affiliations

¹ Department of Clinical Neurosciences (N.S., A.A., M.A., S.B.C., A.D., M.D.H., T.T.S., B.K.M., A.G.), University of Calgary, Canada.
² Department of Internal Medicine (Neurology Division) (N.S.), Health Sciences Center, University of Manitoba, Winnipeg, Canada.
³ Department of Radiology (F.B., M.A., S.B.C., M.D.H., B.K.M.), University of Calgary, Canada.
⁴ Diagnostic and Interventional Neuroradiology, Tours University Hospital, France (F.B.).
⁵ Department of Community Health Sciences (A.A., M.A., S.B.C., M.D.H., T.T.S., B.K.M., A.G.), University of Calgary, Canada.
⁶ Department of Clinical Neurosciences, Université de Montréal, Canada (Y.D., A.Y.P.).
⁷ Department of Medicine, Hurvitz Brain Sciences Program, Sunnybrook Health Sciences Centre (H.K., R.H.S.), University of Toronto, Canada.
⁸ Division of Neurology, Department of Medicine, University of Alberta, Edmonton, Canada (B.H.B.).
⁹ Division of Neurology, Department of Medicine, Queen's University, Kingston, Canada (R.A.).
¹⁰ Department of Neurology, Université de Sherbrooke, Canada (F.M.).
¹¹ Queen Elizabeth Health Sciences Centre, Halifax, Canada (G.G.).
¹² Department of Neurosciences, Kelowna General Hospital, Canada (A.T.).
¹³ Department of Medicine, McMaster University, Hamilton, Canada (L.C.).
¹⁴ Department of Medicine, and Ottawa Hospital Research Institute, University of Ottawa, Canada (D.D., M. Shamy).
¹⁵ Department of Neurosciences, University of British Columbia, Canada (G.M., T.S.F.).
¹⁶ Department of Neurology, London Health Sciences Centre and Western University, Canada (J.M.).
¹⁷ Department of Neurology (A.P.), University of Toronto, Canada.
¹⁸ Department of Radiology (J.J.S.), Health Sciences Center, University of Manitoba, Winnipeg, Canada.
¹⁹ Department of Medicine, Queen Elizabeth Health Sciences Centre, Canada (H.W.).
²⁰ Department of Medicine, Medicine Hat Regional Hospital, Canada (A.M.).
²¹ Department of Neurology, Grey Nuns Community Hospital, Edmonton, Canada (M. Siddiqui).
²² Department of Neurology, St Michael's Hospital, Canada (A.Z.).
²³ Department of Medicine, Red Deer Regional Hospital, Canada (O.I.).
²⁴ Department of Medicine, University of Saskatoon, Canada (G.H.).

PMID: 40123483
DOI: 10.1161/STROKEAHA.124.049512

Clinical Trial

Safety, Functional Disability, Healthcare Utilization, and Quality-of-Life Outcomes in Elderly Receiving Alteplase and Tenecteplase: A Secondary Analysis From the AcT Trial

Nishita Singh et al. Stroke. 2025 May.

. 2025 May;56(5):1169-1179.

doi: 10.1161/STROKEAHA.124.049512. Epub 2025 Mar 24.

Authors

Affiliations

¹ Department of Clinical Neurosciences (N.S., A.A., M.A., S.B.C., A.D., M.D.H., T.T.S., B.K.M., A.G.), University of Calgary, Canada.
² Department of Internal Medicine (Neurology Division) (N.S.), Health Sciences Center, University of Manitoba, Winnipeg, Canada.
³ Department of Radiology (F.B., M.A., S.B.C., M.D.H., B.K.M.), University of Calgary, Canada.
⁴ Diagnostic and Interventional Neuroradiology, Tours University Hospital, France (F.B.).
⁵ Department of Community Health Sciences (A.A., M.A., S.B.C., M.D.H., T.T.S., B.K.M., A.G.), University of Calgary, Canada.
⁶ Department of Clinical Neurosciences, Université de Montréal, Canada (Y.D., A.Y.P.).
⁷ Department of Medicine, Hurvitz Brain Sciences Program, Sunnybrook Health Sciences Centre (H.K., R.H.S.), University of Toronto, Canada.
⁸ Division of Neurology, Department of Medicine, University of Alberta, Edmonton, Canada (B.H.B.).
⁹ Division of Neurology, Department of Medicine, Queen's University, Kingston, Canada (R.A.).
¹⁰ Department of Neurology, Université de Sherbrooke, Canada (F.M.).
¹¹ Queen Elizabeth Health Sciences Centre, Halifax, Canada (G.G.).
¹² Department of Neurosciences, Kelowna General Hospital, Canada (A.T.).
¹³ Department of Medicine, McMaster University, Hamilton, Canada (L.C.).
¹⁴ Department of Medicine, and Ottawa Hospital Research Institute, University of Ottawa, Canada (D.D., M. Shamy).
¹⁵ Department of Neurosciences, University of British Columbia, Canada (G.M., T.S.F.).
¹⁶ Department of Neurology, London Health Sciences Centre and Western University, Canada (J.M.).
¹⁷ Department of Neurology (A.P.), University of Toronto, Canada.
¹⁸ Department of Radiology (J.J.S.), Health Sciences Center, University of Manitoba, Winnipeg, Canada.
¹⁹ Department of Medicine, Queen Elizabeth Health Sciences Centre, Canada (H.W.).
²⁰ Department of Medicine, Medicine Hat Regional Hospital, Canada (A.M.).
²¹ Department of Neurology, Grey Nuns Community Hospital, Edmonton, Canada (M. Siddiqui).
²² Department of Neurology, St Michael's Hospital, Canada (A.Z.).
²³ Department of Medicine, Red Deer Regional Hospital, Canada (O.I.).
²⁴ Department of Medicine, University of Saskatoon, Canada (G.H.).

PMID: 40123483
DOI: 10.1161/STROKEAHA.124.049512

Abstract

Background: Older age has been associated with overall poorer outcomes in acute ischemic stroke. We compared (1) outcomes in various health-related domains among patients <80 years and ≥80 years presenting with acute ischemic stroke and (2) whether outcomes differ between intravenous TNK (tenecteplase) versus alteplase.

Methods: Data are from patients included in AcT (Alteplase Compared to Tenecteplase in Patients With Acute Ischemic Stroke), a pragmatic, registry-linked, phase 3 randomized controlled trial comparing TNK with alteplase. Outcomes included functional disability (per 90-day modified Rankin Scale), safety (24-hour symptomatic intracerebral hemorrhage, 90-day mortality rates), health care utilization (discharge destination, length of stay, thrombectomy rate), and quality of life measures (EQ-5D-5L [EuroQol 5-Dimension 5-Level Scale]). With an a priori plan, patients aged <80 years were compared with those ≥80 years at symptom onset. Mixed effects Poisson regression was used to assess (1) the association of age with outcomes and (2) if these associations were modified by thrombolytic administered (TNK versus alteplase), after adjusting for sex, and baseline stroke severity.

Results: Of the 1577 patients, 1034 (65.6%; 520: TNK and 514: alteplase) were <80 years and 543 (34.4%; 286: TNK and 257: alteplase) were ≥80 years of age. Baseline characteristics in the 2 groups were similar except for sex 40% female in <80 years group versus 62.8% female in ≥80 years. There was no difference in rates of symptomatic intracranial hemorrhage (3.5% versus 3.1%). Patients in the ≥80 years group had significantly lower rates of excellent functional outcome, return to baseline status, higher mortality, and lower quality-of-life outcomes as compared with the <80 years group. Length of hospital stay was similar between the 2 groups but, patients in the ≥80 years age group had significantly lower rates of endovascular treatment utilization. Type of thrombolytic agent (TNK versus alteplase) did not modify the association between age and primary clinical outcome (P_interaction=0.22).

Conclusions: Similar to alteplase, increasing age was associated with poorer functional outcomes with TNK. Rates of angiographic and bleeding outcomes were similar between patients <80 and ≥80 years.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03889249.

Keywords: aged, 80 and over; cerebral hemorrhage; ischemic stroke; quality of life; tenecteplase; thrombolysis.

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Conflict of interest statement

Dr Almekhlafi reports compensation from Palmera Medical Inc for other services. Dr Catanese reports compensation from Hoffmann-La Roche Limited for consultant services. Dr Pikula reports grants from Department of Medicine, University of Toronto. Dr Poppe reports grants from Fondation Brain Canada, the Heart and Stroke Foundation of Canada, and Canadian Institutes of Health Research. Dr Field reports compensation from Canadian Medical Protective Association for expert witness services; compensation from HLS Therapeutics, AstraZeneca Canada, and Novartis for consultant services; service as a board member for Destine Health and Vancouver General Hospital Foundation. Dr Demchuk reports compensation from Lumosa and Philips for data and safety monitoring services; compensation from AstraZeneca Canada for other services; compensation from NovaSignal and Hoffmann-La Roche for consultant services; a patent issued for Stroke imaging software licensed to Circle NVI; and stock holdings in Circle NVI. Dr Swartz reports grants from National Institutes of Health and Canadian Institutes of Health Research; compensation from F. Hoffmann-La Roche for consultant services; and compensation from Sunnybrook Research Institute for other services. Dr Hill reports grants from Canadian Institutes of Health Research, NoNO Inc, Medtronic, and Boehringer Ingelheim; stock options in Basking Bioscience LLC; and compensation from Merck for end point review committee services. Dr Menon has stock options in Circle NVI and has consulted for Biogen and Boehringer Ingelheim. Dr Coutts is the principal investigator of the TEMPO-2 trial (Tenecteplase Versus Standard of Care for Minor Ischemic Stroke With Proven Occlusion), for which Boehringer Ingelheim provides the study drug (tenecteplase). Dr Shankar has a grant from Medtronic to the University of Manitoba. Dr Ganesh reports consulting fees and honoraria from Alexion, AlphaSights, Atheneum, Biogen, Consortium of Canadian Centres for Clinical Cognitive Research (C5R), CTC Communications Corp, Figure 1, MD Analytics, Servier Canada, and Techspert; research support from Alberta Innovates, the Alzheimer Society of Canada, the Alzheimer Society of Alberta and Northwest Territories, Brain Canada, the Canadian Institutes of Health Research, Campus Alberta Neuroscience, the Government of Canada INOVAIT and New Frontiers in Research programs, the France-Canada Research Fund, the Heart and Stroke Foundation of Canada, Microvention, MSI Foundation, and Panmure House; and stock/stock options from SnapDx Inc and Collavidence Inc (Let’s Get Proof)—all outside the scope of the published work. The other authors report no conflicts.

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Safety, Functional Disability, Healthcare Utilization, and Quality-of-Life Outcomes in Elderly Receiving Alteplase and Tenecteplase: A Secondary Analysis From the AcT Trial

Affiliations

Safety, Functional Disability, Healthcare Utilization, and Quality-of-Life Outcomes in Elderly Receiving Alteplase and Tenecteplase: A Secondary Analysis From the AcT Trial

Authors

Affiliations

Abstract

Conflict of interest statement

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Associated data

LinkOut - more resources

Full Text Sources

Medical