Faster Thrombolysis Is Associated With Improved Cognitive Outcomes in Patients With Acute Ischemic Stroke Treated With Alteplase and Tenecteplase: A Substudy of the AcT Trial

Sajeevan Sujanthan^{1

2}, Gayathiri Rajkumar², Katie N Dainty³, Morgan Barense⁴, Krista L Lanctot⁵, Adrian M Owen⁶, Nishita Singh⁷, Brian H Buck⁸, Houman Khosravani^{5

2}, Shelagh B Coutts⁹, Mohammed Almekhlafi⁹, Ramana Appireddy¹⁰, Aleksander Tkach¹¹, Luciana Catanese¹², Dar Dowlatshahi¹³, Jennifer Mandzia¹⁴, Aleksander Pikula¹⁵, Heather Williams¹⁶, Thalia S Field¹⁷, Alejandro Manosalva¹⁸, Muzaffar Siddiqui¹⁹, Gary Hunter²⁰, MacKenzie Horn⁹, Fouzi Bala²¹, Michael D Hill⁹, Michel Shamy¹³, Aravind Ganesh⁹, Tolulope Sajobi⁹, Bijoy K Menon⁹, Richard H Swartz^{1

22

2}; AcT Trial Investigators

Affiliations

¹ Faculty of Graduate Studies, Institute of Medical Sciences (S.S., R.H.S.), University of Toronto, ON, Canada.
² Department of Medicine (Neurology), Sunnybrook Health Science Centre, Hurvitz Brain Sciences Program, Sandra Black Centre for Brain Resilience and Recovery, Toronto, ON, Canada (S.S., G.R., H.K., R.H.S.).
³ Institute of Health Policy, Management and Evaluation (K.N.D.), University of Toronto, ON, Canada.
⁴ Department of Psychology, Rotman Research Institute, Baycrest Heath Sciences (M.B.), University of Toronto, ON, Canada.
⁵ Department of Physiology & Pharmacology, Psychology (K.L.L., H.K.), University of Toronto, ON, Canada.
⁶ Department of Psychiatry, and Pharmacology and Toxicology (A.M.O.), Western University, ON, Canada.
⁷ Rady Faculty of Medicine, Division of Neurology, University of Manitoba, Winnipeg, Canada (N.S.).
⁸ Division of Neurology, Department of Medicine, University of Alberta, Edmonton, Canada (B.H.B.).
⁹ Department of Clinical Neurosciences, Cumming School of Medicine, Hotchkiss Brain Institute, University of Calgary, AB, Canada (S.B.C., M.A., M.H., M.D.H., A.G., T.S., B.K.M.).
¹⁰ Division of Neurology, Department of Medicine, Queen's University, Kingston, ON, Canada (R.A.).
¹¹ Department of Neuroscience, Kelowna General Hospital, BC, Canada (A.T.).
¹² Division of Neurology, Hamilton Health Sciences Centre and McMaster University, ON, Canada (L.C.).
¹³ Department of Medicine, University of Ottawa, ON, Canada (D.D., M. Shamy).
¹⁴ London Health Sciences Centre (J.M.), Western University, ON, Canada.
¹⁵ Toronto Western Hospital (A.P.), University of Toronto, ON, Canada.
¹⁶ Queen Elizabeth Hospital, Charlottetown, PE, Canada (H.W.).
¹⁷ Division of Neurology, The University of British Columbia, Vancouver, Canada (T.S.F.).
¹⁸ Medicine Hat Regional Hospital, AB, Canada (A.M.).
¹⁹ Grey Nuns Community Hospital, Edmonton, AB, Canada (M. Siddiqui).
²⁰ University of Saskatchewan, Saskatoon, Canada (G.H.).
²¹ Diagnostic and Interventional Neuroradiology Department, University Hospital of Tours, France (F.B.).
²² Faculty of Medicine, Division of Neurology, Department of Medicine (R.H.S.), University of Toronto, ON, Canada.

PMID: 40677228
DOI: 10.1161/STROKEAHA.125.051670

Observational Study

Faster Thrombolysis Is Associated With Improved Cognitive Outcomes in Patients With Acute Ischemic Stroke Treated With Alteplase and Tenecteplase: A Substudy of the AcT Trial

Sajeevan Sujanthan et al. Stroke. 2025 Oct.

. 2025 Oct;56(10):2858-2865.

doi: 10.1161/STROKEAHA.125.051670. Epub 2025 Jul 18.

Authors

Affiliations

¹ Faculty of Graduate Studies, Institute of Medical Sciences (S.S., R.H.S.), University of Toronto, ON, Canada.
² Department of Medicine (Neurology), Sunnybrook Health Science Centre, Hurvitz Brain Sciences Program, Sandra Black Centre for Brain Resilience and Recovery, Toronto, ON, Canada (S.S., G.R., H.K., R.H.S.).
³ Institute of Health Policy, Management and Evaluation (K.N.D.), University of Toronto, ON, Canada.
⁴ Department of Psychology, Rotman Research Institute, Baycrest Heath Sciences (M.B.), University of Toronto, ON, Canada.
⁵ Department of Physiology & Pharmacology, Psychology (K.L.L., H.K.), University of Toronto, ON, Canada.
⁶ Department of Psychiatry, and Pharmacology and Toxicology (A.M.O.), Western University, ON, Canada.
⁷ Rady Faculty of Medicine, Division of Neurology, University of Manitoba, Winnipeg, Canada (N.S.).
⁸ Division of Neurology, Department of Medicine, University of Alberta, Edmonton, Canada (B.H.B.).
⁹ Department of Clinical Neurosciences, Cumming School of Medicine, Hotchkiss Brain Institute, University of Calgary, AB, Canada (S.B.C., M.A., M.H., M.D.H., A.G., T.S., B.K.M.).
¹⁰ Division of Neurology, Department of Medicine, Queen's University, Kingston, ON, Canada (R.A.).
¹¹ Department of Neuroscience, Kelowna General Hospital, BC, Canada (A.T.).
¹² Division of Neurology, Hamilton Health Sciences Centre and McMaster University, ON, Canada (L.C.).
¹³ Department of Medicine, University of Ottawa, ON, Canada (D.D., M. Shamy).
¹⁴ London Health Sciences Centre (J.M.), Western University, ON, Canada.
¹⁵ Toronto Western Hospital (A.P.), University of Toronto, ON, Canada.
¹⁶ Queen Elizabeth Hospital, Charlottetown, PE, Canada (H.W.).
¹⁷ Division of Neurology, The University of British Columbia, Vancouver, Canada (T.S.F.).
¹⁸ Medicine Hat Regional Hospital, AB, Canada (A.M.).
¹⁹ Grey Nuns Community Hospital, Edmonton, AB, Canada (M. Siddiqui).
²⁰ University of Saskatchewan, Saskatoon, Canada (G.H.).
²¹ Diagnostic and Interventional Neuroradiology Department, University Hospital of Tours, France (F.B.).
²² Faculty of Medicine, Division of Neurology, Department of Medicine (R.H.S.), University of Toronto, ON, Canada.

PMID: 40677228
DOI: 10.1161/STROKEAHA.125.051670

Abstract

Background: Cognitive impairment after stroke is linked with poorer functional outcomes. Faster thrombolytic improves recanalization, 3-month functional recovery, and in-hospital survival. We examined whether faster treatment times from door-to-needle and symptom onset-to-needle (OTN) impacted cognition.

Methods: This study is a prespecified secondary observational cohort analysis of the AcT randomized clinical trial (Alteplase Compared to Tenecteplase; URL: https://www.clinicaltrials.gov; Unique identifier: NCT03889249) data. Eligible participants were English-speaking individuals who independently completed the trial's primary outcome and were recruited from 18 stroke centers within Canada. Prospective cognitive outcomes were collected at 90 to 180 days using a Telephone Montreal Cognitive Assessment (T-MoCA range, 0-22; <17 impairment). The primary aim was to assess cognitive performance and its relationship with treatment times (door-to-needle and OTN) at 90 to 180 days. Linear and logistic regression analyses were used to evaluate the relationship, adjusting for treatment allocation, age, sex, baseline National Institutes of Health Stroke Scale, education, ethnicity, and occlusion location.

Results: Three hundred ninety-nine (50%) of 791 eligible subjects completed the T-MoCA. The mean age was 66±13 years, 38.8% were female, and the mean T-MoCA score was 16±4. Shorter OTN times (but not door-to-needle) were associated with higher T-MoCA scores on linear regression (β, -0.009 [95% CI, -0.016 to -0.002]) and with increased odds of T-MoCA impairment for every 1-minute increase on logistic regression (odds ratio, 1.005 [95% CI, 1.001-1.009]). There was no difference between the alteplase and tenecteplase subgroups in the relationship between treatment times and cognition. Each 15-minute reduction in OTN was associated with a 7.3% reduction in the probability of impairment (score <17) on the T-MoCA.

Conclusions: Faster OTN time, with either alteplase or tenecteplase, was associated with higher T-MoCA scores and reduced the likelihood of impairment at 90 days. Faster thrombolytic treatment may reduce cognitive burden after stroke.

Keywords: cognitive dysfunction; fibrinolytic agents; ischemia; ischemic stroke; time-to-treatment.

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Conflict of interest statement

Dr Swartz reports ownership shares in FollowMD, Inc, a virtual vascular risk reduction clinic, has participated in an advisory board for Hoffmann-La Roche Ltd, and holds the Bastable-Potts Chair in Stroke Research at Sunnybrook HSC, University of Toronto. Dr Dainty is employed by North York General Hospital and receives compensation from Philips for consultant services. Dr Singh reports salary support from the Heart and Stroke Foundation of Canada, Research Manitoba, and the University of Manitoba. Dr Catanese reports grants from Servier Pharmaceuticals LLC, employment by Hamilton Health Sciences and McMaster University, and receives compensation from Hoffmann-La Roche Ltd for consultant services. Dr Pikula reports grants from the Department of Medicine, University of Toronto. Dr Field reports service as a board member of Destine Health, the Vancouver General Hospital/University of British Columbia Hospital Foundation, and the Vancouver General Hospital Foundation; receives compensation from HLS Therapeutics, Bayer, Novartis, and AstraZeneca Canada for consultant services; receives compensation from Canadian Medical Protective Association for expert witness services; and receives grants from Boehringer Ingelheim. Dr Hill reports stock options in Basking Bioscience LLC; employment by the University of Calgary; and receives grants from Boehringer Ingelheim, NoNO, Inc, Medtronic, and Canadian Institutes of Health Research. Dr Ganesh received honoraria from Alexion, Biogen, Eisai, and Servier Canada; grant support from the Alzheimer Society of Canada, the Alzheimer Society of Alberta and Northwest Territories, and the Heart and Stroke Foundation of Canada; and stock options in SnapDx, Inc, and Let’s Get Proof (Collavidence, Inc). The other authors report no conflicts.

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Faster Thrombolysis Is Associated With Improved Cognitive Outcomes in Patients With Acute Ischemic Stroke Treated With Alteplase and Tenecteplase: A Substudy of the AcT Trial

Affiliations

Faster Thrombolysis Is Associated With Improved Cognitive Outcomes in Patients With Acute Ischemic Stroke Treated With Alteplase and Tenecteplase: A Substudy of the AcT Trial

Authors

Affiliations

Abstract

Conflict of interest statement

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LinkOut - more resources

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Medical