Safety and efficacy of tenecteplase versus alteplase in stroke patients with carotid tandem lesions: Results from the AcT trial

Fouzi Bala; Mohammed Almekhlafi; Nishita Singh; Ibrahim Alhabli; Ayoola Ademola; Shelagh B Coutts; Yan Deschaintre; Houman Khosravani; Ramana Appireddy; Francois Moreau; Stephen Phillips; Gord Gubitz; Aleksander Tkach; Luciana Catanese; Dar Dowlatshahi; George Medvedev; Jennifer Mandzia; Aleksandra Pikula; Jay Shankar; Heather Williams; Thalia S Field; Alejandro Manosalva; Muzaffar Siddiqui; Atif Zafar; Oje Imoukhoude; Gary Hunter; Faysal Benali; MacKenzie Horn; Michael D Hill; Michel Shamy; Tolulope T Sajobi; Brian H Buck; Richard H Swartz; Bijoy K Menon; Alexandre Y Poppe

doi:10.1177/17474930231205208

Safety and efficacy of tenecteplase versus alteplase in stroke patients with carotid tandem lesions: Results from the AcT trial

Int J Stroke. 2024 Mar;19(3):322-330. doi: 10.1177/17474930231205208. Epub 2023 Oct 6.

Authors

Fouzi Bala^{1

2}, Mohammed Almekhlafi¹, Nishita Singh^{1

3}, Ibrahim Alhabli¹, Ayoola Ademola¹, Shelagh B Coutts¹, Yan Deschaintre⁴, Houman Khosravani⁵, Ramana Appireddy⁶, Francois Moreau⁷, Stephen Phillips⁸, Gord Gubitz⁸, Aleksander Tkach⁹, Luciana Catanese¹⁰, Dar Dowlatshahi¹¹, George Medvedev^{12

13}, Jennifer Mandzia¹⁴, Aleksandra Pikula¹⁵, Jay Shankar¹⁶, Heather Williams¹⁷, Thalia S Field¹⁸, Alejandro Manosalva¹⁹, Muzaffar Siddiqui²⁰, Atif Zafar²¹, Oje Imoukhoude²², Gary Hunter²³, Faysal Benali¹, MacKenzie Horn¹, Michael D Hill¹, Michel Shamy¹¹, Tolulope T Sajobi¹, Brian H Buck²⁴, Richard H Swartz⁵, Bijoy K Menon¹, Alexandre Y Poppe⁴

Affiliations

¹ Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada.
² Diagnostic and Interventional Neuroradiology Department, University Hospital of Tours, Tours, France.
³ Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
⁴ Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, QC, Canada.
⁵ Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
⁶ Division of Neurology, Department of Medicine, Queen's University, Kingston, ON, Canada.
⁷ Université de Sherbrooke, Sherbrooke, QC, Canada.
⁸ Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada.
⁹ Kelowna General Hospital, Kelowna, BC, Canada.
¹⁰ Hamilton Health Sciences, McMaster University, Hamilton, ON, Canada.
¹¹ Department of Medicine, University of Ottawa, Ottawa, ON, Canada.
¹² The University of British Columbia, Vancouver, BC, Canada.
¹³ Fraser Health Authority, New Westminster, BC, Canada.
¹⁴ London Health Sciences Centre, Western University, London, ON, Canada.
¹⁵ Toronto Western Hospital, University of Toronto, Toronto, ON, Canada.
¹⁶ University of Manitoba, Winnipeg, MB, Canada.
¹⁷ Queen Elizabeth Hospital, Charlottetown, PEI, Canada.
¹⁸ Vancouver Stroke Program, Division of Neurology, The University of British Columbia, Vancouver, BC, Canada.
¹⁹ Medicine Hat Regional Hospital, Medicine Hat, AB, Canada.
²⁰ Grey Nuns Community Hospital, Edmonton, AB, Canada.
²¹ St. Michael's Hospital, Toronto, ON, Canada.
²² Red Deer Regional Hospital Centre, Red Deer, AB, Canada.
²³ University of Saskatchewan, Saskatoon, SK, Canada.
²⁴ Division of Neurology, Department of Medicine, University of Alberta, Edmonton, AB, Canada.

Abstract

Background: Carotid tandem lesions ((TL) ⩾70% stenosis or occlusion) account for 15-20% of acute stroke with large vessel occlusion.

Aims: We investigated the safety and efficacy of intravenous tenecteplase (0.25 mg/kg) versus intravenous alteplase (0.9 mg/kg) in patients with carotid TL.

Methods: This is a substudy of the alteplase compared with the tenecteplase trial. Patients with ⩾70% stenosis of the extracranial internal carotid artery (ICA) and concomitant occlusion of the intracranial ICA, M1 or M2 segments of the middle cerebral artery on baseline computed tomography angiography (CTA) were included. Primary outcome was 90-day-modified Rankin Scale (mRS) 0-1. Secondary outcomes were mRS 0-2, mortality, and symptomatic ICH (sICH). Angiographic outcomes were successful recanalization (revised Arterial Occlusive Lesion (rAOL) 2b-3) on first and successful reperfusion (eTICI 2b-3) on final angiographic acquisitions. Multivariable mixed-effects logistic regression was performed.

Results: Among 1577 alteplase versus tenecteplase randomized controlled trial (AcT) patients, 128 (18.8%) had carotid TL. Of these, 93 (72.7%) underwent intravenous thrombolysis plus endovascular thrombectomy (IVT + EVT), while 35 (27.3%) were treated with IVT alone. In the IVT + EVT group, tenecteplase was associated with higher odds of 90-day-mRS 0-1 (46.0% vs. 32.6%, adjusted OR (aOR) 3.21; 95% CI = 1.06-9.71) compared with alteplase. No statistically significant differences in rates of mRS 0-2 (aOR 1.53; 95% CI = 0.51-4.55), initial rAOL 2b-3 (16.3% vs. 28.6%), final eTICI 2b-3 (83.7% vs. 85.7%), and mortality (18.0% vs. 16.3%) were found. SICH only occurred in one patient. There were no differences in outcomes between thrombolytic agents in the IVT-only group.

Conclusion: In patients with carotid TL treated with EVT, intravenous tenecteplase may be associated with similar or better clinical outcomes, similar angiographic reperfusion rates, and safety outcomes as compared with alteplase.

Keywords: Stroke; endovascular; tandem; tenecteplase.

Publication types

Clinical Trial

MeSH terms

Arterial Occlusive Diseases*
Brain Ischemia* / therapy
Constriction, Pathologic
Endovascular Procedures* / methods
Fibrinolytic Agents / adverse effects
Humans
Stroke* / therapy
Tenecteplase / therapeutic use
Thrombectomy / methods
Tissue Plasminogen Activator / adverse effects
Treatment Outcome

Substances

Fibrinolytic Agents
Tenecteplase
Tissue Plasminogen Activator