Endovascular thrombectomy for acute ischaemic stroke with established large infarct (TENSION): 12-month outcomes of a multicentre, open-label, randomised trial.

BACKGROUND

Long-term data showing the benefits of endovascular thrombectomy for stroke with large infarct are scarce. The TENSION trial showed the safety and efficacy of endovascular thrombectomy in patients with ischaemic stroke and large infarct at 90 days. We aimed to investigate the safety and efficacy at 12 months of endovascular thrombectomy in patients who were enrolled in the TENSION trial.

METHODS

TENSION was an open-label, blinded endpoint, randomised trial done at 40 hospitals across Europe and one hospital in Canada. We included patients (aged ≥18 years) with acute ischaemic stroke due to large vessel occlusion in the anterior circulation and who had a large infarct, as indicated by an Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) of 3-5 on standard-of-care stroke imaging. We randomly assigned patients (1:1) to receive either endovascular thrombectomy with medical treatment or medical treatment only up to 12 h from stroke onset. The primary outcome was functional outcome across the entire range of the modified Rankin Scale at 90 days. Here, we report the prespecified 12-month follow-up analyses for functional outcome (using the simplified modified Rankin Scale questionnaire), quality of life (using the Patient-Reported Outcomes Measurement Information System 10-item [PROMIS-10] and EQ-5D questionnaires), post-stroke anxiety and depression (using the Patient Health Questionnaire-4 [PHQ-4]), and overall survival. Outcomes (except survival) were assessed in the intention-to-treat population; the survival analysis was based on treatment received. This trial is registered with ClinicalTrials.gov, NCT03094715, and is completed.

FINDINGS

We enrolled patients between July 17, 2018, and Feb 21, 2023, when the trial was stopped early for efficacy. 253 patients were randomly assigned, 125 (49%) to endovascular thrombectomy and 128 (51%) to medical treatment only. Median follow-up was 8·36 months (IQR 0·02-12·00). Endovascular thrombectomy was associated with a shift in the distribution of scores on the modified Rankin Scale towards better functional outcome at 12 months (adjusted common odds ratio 2·39 [95% CI 1·47-3·90]). Endovascular thrombectomy was also associated with a better quality of life compared with medical treatment only, as reflected by median scores on the EQ-5D questionnaire index (0·7 [IQR 0·4-0·9] vs 0·4 [0·2-0·7]), median scores for health status on the EQ-5D questionnaire visual analogue scale (50 [IQR 35-70] vs 30 [5-60]), and median global physical health scores on the PROMIS-10 questionnaire (T-score 39·8 [IQR 37·4-50·8] vs 37·4 [32·4-44·9]); although there was not enough evidence to suggest a difference between groups in global mental health scores on PROMIS-10 (41·1 [IQR 36·3-48·3] vs 38·8 [31·3-44·7]) or the numbers of patients reporting anxiety (13 [22%] of 58 vs 15 [42%] of 36) and depression (18 [31%] vs 18 [50%]) on PHQ-4. Overall survival was slightly better in the endovascular thrombectomy group compared with medical treatment only (adjusted hazard ratio 0·70 [95% CI 0·50-0·99]).

INTERPRETATION

In patients with acute ischaemic stroke from large vessel occlusion with established large infarct, compared with medical treatment only, endovascular thrombectomy was associated at 12 months after stroke with better functional outcome, quality of life, and overall survival. These findings suggest that the benefits of endovascular thrombectomy in patients with an ischaemic stroke and a large infarct are sustained in the long term and support the use of endovascular thrombectomy in these patients.

FUNDING

European Union Horizon 2020 Research and Innovation Programme.

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.

Déclaration de conflit d'intérêts

Declaration of interests MB reports funding from the European Union Horizon 2020 and Deutsche Forschungsgemeinschaft (payments to the institution); honoraria for lectures from Novartis, Boehringer Ingelheim, and Seagen; consulting fees from NeuroScios and Boehringer Ingelheim; and a role as Editor-in-Chief of Clinical Neuroradiology (Springer), outside the submitted work. JF reports funding from the European Commission; personal consulting fees from Acandis, Cerenovus, Medtronic, Microvention, Phenox, Roche, and Stryker; consulting at Philips (no payments); payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Penumbra and Tonbridge; support for attending meetings or travel from Medtronic and Penumbra; and stock or stock options from Tegus medical, eppdata, and Vastrax, outside the submitted work. JF also reports participation in a Data Safety Monitoring Board (DSMB) or Advisory Board at Phenox (personal fees) and Stryker (personal fees), and a role as past president of ESMINT. SB reports funding from the EU Horizon 2020 research and innovation programme (payments made to the institution; support for attending meetings or travel), outside the submitted work. AHA reports unrestricted research grants from Boehringer Ingelheim and honoraria for lectures from BMS/Pfizer, Teva, Roche, Abbvie, Lundbeck, Novartis, outside the submitted work. AHA also reports participation in Advisory Boards for MSD, BMS/Pfizer, Lundbeck, Lilly, and Abbvie. BF reports research grants from Carlos III Institute of Health (ISCIII), personal payment for educational lectures from Servicio Madrileño de Salud, payment to the institution for lectures from Euromedice, personal payment for educational lectures from Takeda, support for attending meetings from Daichii Sankyo, and receipt of materials for research from Abbot, outside the submitted work. MDH reports funding from Nil, a grant to the University of Calgary for the TEMPO-2 trial from Boehringer Ingelheim, a grant to the University of Calgary from Biogen, a grant to the University of Calgary for the ESCAPE-NA1 trial and ESCAPE-NEXT trial from NoNO, a grant to the University of Calgary for the ESCAPE-NA1 trial and ESCAPE-NEXT trial from the Canadian Institute for Health Research, a grant to the University of Calgary for the HERMES collaboration from Medtronic, and a grant to the University of Calgary for the QuICR Alberta Stroke Program; some of the funds were used for the ESCAPE-NA1 trial from Alberta Innovates. MDH also reports consulting fees from Sun Pharma Brainsgate (paid work for adjudication of clinical trial outcomes), US Patent 62/086,077 (licensed to Circle NVI), US Patent 10,916,346 (licensed to Circle NVI), and private stock ownership from Circle and PUreWeb, outside the submitted work. MDH reports participation as DSMC Chair of the RACECAT trial (end 2020), participation as DSMC Chair of the Oncovir Hiltonel trial (ongoing), participation as DSMC Chair of the DUMAS trial (ongoing), participation as DSMB member of the ARTESIA trial (ongoing), participation as DSMB member of the BRAIN-AF trial (ongoing), a role as President of the Canadian Neurological Sciences Federation (not for profit), and as Board Member of the Canadian Stroke Consortium (not for profit). AK reports grants from the European Commission for the TENSION study (payment to the institution), outside the submitted work. LP reports consulting fees from Balt, consulting fees from Microvention, consulting fees from Phenox, and support for attending meetings or travel for the TENSION investigator meeting (transport and accommodation was reimbursed by the organization), outside the submitted work. CZS reports grants from Health Research Foundation of Central Denmark Region, outside the submitted work. RAB reports speakers fees from Novo Nordisk and Beyer, outside the submitted work. HD reports financial compensation for the start-up fee and the obligatory payment to the hospital administration paid by the sponsor (Medical University Heidelberg) to the Clinical Division (no personal payments), personal consulting fees from Stryker, speakers honorary from Medtronic, and support for attending meetings or travel from Medtronic, outside the submitted work. HD also reports a role as past President of the Austrian Society of Interventional Radiology and past president Austrian Society of Neuroradiology. FD reports consulting fees from Cerenovus, Balt, Cerus Endovascular, and Microvention; payment for expert testimony from Cerenovus; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Cerenovus, Stryker, Acandis, Asahi, Penumbra, Medtronic, Tonbridge, Inspire, and Q'Apel, outside the submitted work. FD also reports participation in a DSMB or Advisory Board at Cerenovus and Microvention and previous roles as Associate Editor for Journal of Interventional Surgery, Journal of Clinical Medicine, and Clinical Neuroradiology. FF reports consulting fees from eppdata and support for attending meetings or travel from Microvention, Medtronic, Cerebrovascular Research and Education Foundation, and Acandis, outside the submitted work. SG reports consulting fees from eppdata, outside the submitted work. CH reports consulting fees from Brainomix and lecture fees from Stryker, outside the submitted work. SH-J reports funding for data collection and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Terumo, outside the submitted work. MG reports research grants from Medtronic and Cerenovus (payments to the University of Calgary); royalties or licenses from Microvention (systems of intracranial access); personal consulting fees from Microvention, Medtronic, Stryker, Mentice, Philips, and Penumbra; and stock or stock options from Circle Neurovascular, outside the submitted work. FCK was chair of the German Stroke Registry (unpaid). RM reports payments for stroke lecture from TMC Academy, outside the submitted work. MM reports grants from Balt, Medtronic, MicroVention, and Stryker; consulting fees from Siemens; and support for attending meetings or travel from Europa Group, outside the submitted work. SM-H reports consulting fees from Terumo and Boston Scientific Corporation and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Terumo and Boston Scientific Corporation, outside the submitted work. NM reports provision of study materials, outside the submitted work. PP reports support for attending meetings or travel for the TENSION investigator meeting (transport and accommodation was reimbursed by the organisation), outside the submitted work. MP reports grants from the German Research Foundation, speaker honoraria unrelated from Merck Serono and Bayer, and support for attending meetings or travel from Merck Serono (travel reimbursement) and Bayer (travel reimbursement), outside the submitted work. VP reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Boehringer Ingelheim, Daichii Sankyo, AstraZeneca and BMS, and support for attending meetings or travel from NoNo (travel reimbursement). PAR reports consulting fees to the institution from Boehringer Ingelheim and Bayer, and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Boehringer Ingelheim, Bayer, Pfizer, and BMS (all made to the institution), outside the submitted work. ES reports grants from Hamburg Innovation and Hertie Foundation, outside the submitted work. DFV reports research grants from MicroVention, consulting fees from Medtronic, and paid lectures from Cerenovus/Johnson & Johnson, outside the submitted work. WW reports consulting fees to the institution from Abbvie, and consulting fees to the institution from BMS, GSK, and Servier, outside the submitted work. GT reports funding from the European Commission (EU Horizon 2020 research and innovation programme, payments to the institution); personal consulting fees from Acandis, AstraZeneca, Bayer, Boehringer Ingelheim, and Stryker; and personal payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Acandis, Alexion, Amarin, Bayer, Boehringer Ingelheim, BristolMyersSquibb/Pfizer, Daiichi Sankyo, Stryker, outside the submitted work. GT also reports participation as DSMB member for the TEA Stroke Trial (no payments) and ReSCInD trial (no payments), a role as speaker of the Commission for Cerebrovascular Diseases of the German Society of Neurology (no payments), and member of the Board of Directors of the European Stroke Organisation (no payments). All other declare no competing interests.