T Reiff1, H H Eckstein2, U Mansmann3, O Jansen4, G Fraedrich5, H Mudra6, D Böckler7, M Böhm8, H Brückmann9, E S Debus10, J Fiehler11, W Lang12, K Mathias13, E B Ringelstein14, J Schmidli15, R Stingele16, R Zahn17, T Zeller18, A Hetzel19, U Bodechtel20, A Binder21, J Glahn22, W Hacke1, P A Ringleb1. 1. 1 Department of Neurology, University Hospital of Heidelberg, Heidelberg, Germany. 2. 2 Department for Vascular and Endovascular Surgery, Technical University of Munich, Munich, Germany. 3. 3 Institute of Medical Informatics, Biometry and Epidemiology, Ludwig Maximilian University Munich, Munich, Germany. 4. 4 Department of Radiology and Neuroradiology, UKSH Campus Kiel, Kiel, Germany. 5. 5 Department of Vascular Surgery, University Hospital of Innsbruck, Innsbruck, Austria. 6. 6 Department of Internal Medicine, Städtisches Klinikum München-Neuperlach, Munich, Germany. 7. 7 Department of Vascular Surgery, University Hospital of Heidelberg, Heidelberg, Germany. 8. 8 Department of Internal Medicine, University Hospital of Homburg/Saar, Homburg, Germany. 9. 9 Department of Neuroradiology, Ludwig-Maximilians-Universität, Munich, Germany. 10. 10 Department of Vascular Surgery, University Hospital of Hamburg, Hamburg, Germany. 11. 11 Department of Neuroradiology, University Hospital of Hamburg, Hamburg, Germany. 12. 12 Department of Vascular Surgery, University Hospital Erlangen, Erlangen, Germany. 13. 13 Department of Radiology, Klinikum Dortmund, Dortmund, Germany. 14. 14 Department of Neurology, University Hospital of Münster, Münster, Germany. 15. 15 Department of Vascular Surgery, University Hospital of Bern, Bern, Switzerland. 16. 16 Department of Neurology, University of Kiel, Kiel, Germany. 17. 17 Department of Internal Medicine, Klinikum Ludwigshafen, Ludwigshafen, Germany. 18. 18 Department of Angiology, University Hospital Freiburg, Bad Krozingen, Germany. 19. 19 Department of Neurology, University Hospital Freiburg, Freiburg, Germany. 20. 20 Department of Neurology, University Hospital of Dresden, Dresden, Germany. 21. 21 Department of Neurology, UKSH Campus Kiel, Kiel, Germany. 22. 22 Department of Neurology, Johannes Wesling Klinikum, Minden, Germany.
Abstract
BACKGROUND: Treatment of individuals with asymptomatic carotid artery stenosis is still handled controversially. Recommendations for treatment of asymptomatic carotid stenosis with carotid endarterectomy (CEA) are based on trials having recruited patients more than 15 years ago. Registry data indicate that advances in best medical treatment (BMT) may lead to a markedly decreasing risk of stroke in asymptomatic carotid stenosis. The aim of the SPACE-2 trial (ISRCTN78592017) was to compare the stroke preventive effects of BMT alone with that of BMT in combination with CEA or carotid artery stenting (CAS), respectively, in patients with asymptomatic carotid artery stenosis of ≥70% European Carotid Surgery Trial (ECST) criteria. METHODS: SPACE-2 is a randomized, controlled, multicenter, open study. A major secondary endpoint was the cumulative rate of any stroke (ischemic or hemorrhagic) or death from any cause within 30 days plus an ipsilateral ischemic stroke within one year of follow-up. Safety was assessed as the rate of any stroke and death from any cause within 30 days after CEA or CAS. Protocol changes had to be implemented. The results on the one-year period after treatment are reported. FINDINGS: It was planned to enroll 3550 patients. Due to low recruitment, the enrollment of patients was stopped prematurely after randomization of 513 patients in 36 centers to CEA (n = 203), CAS (n = 197), or BMT (n = 113). The one-year rate of the major secondary endpoint did not significantly differ between groups (CEA 2.5%, CAS 3.0%, BMT 0.9%; p = 0.530) as well as rates of any stroke (CEA 3.9%, CAS 4.1%, BMT 0.9%; p = 0.256) and all-cause mortality (CEA 2.5%, CAS 1.0%, BMT 3.5%; p = 0.304). About half of all strokes occurred in the peri-interventional period. Higher albeit statistically non-significant rates of restenosis occurred in the stenting group (CEA 2.0% vs. CAS 5.6%; p = 0.068) without evidence of increased stroke rates. INTERPRETATION: The low sample size of this prematurely stopped trial of 513 patients implies that its power is not sufficient to show that CEA or CAS is superior to a modern medical therapy (BMT) in the primary prevention of ischemic stroke in patients with an asymptomatic carotid stenosis up to one year after treatment. Also, no evidence for differences in safety between CAS and CEA during the first year after treatment could be derived. Follow-up will be performed up to five years. Data may be used for pooled analysis with ongoing trials.
RCT Entities:
BACKGROUND: Treatment of individuals with asymptomatic carotid artery stenosis is still handled controversially. Recommendations for treatment of asymptomatic carotid stenosis with carotid endarterectomy (CEA) are based on trials having recruited patients more than 15 years ago. Registry data indicate that advances in best medical treatment (BMT) may lead to a markedly decreasing risk of stroke in asymptomatic carotid stenosis. The aim of the SPACE-2 trial (ISRCTN78592017) was to compare the stroke preventive effects of BMT alone with that of BMT in combination with CEA or carotid artery stenting (CAS), respectively, in patients with asymptomatic carotid artery stenosis of ≥70% European Carotid Surgery Trial (ECST) criteria. METHODS: SPACE-2 is a randomized, controlled, multicenter, open study. A major secondary endpoint was the cumulative rate of any stroke (ischemic or hemorrhagic) or death from any cause within 30 days plus an ipsilateral ischemic stroke within one year of follow-up. Safety was assessed as the rate of any stroke and death from any cause within 30 days after CEA or CAS. Protocol changes had to be implemented. The results on the one-year period after treatment are reported. FINDINGS: It was planned to enroll 3550 patients. Due to low recruitment, the enrollment of patients was stopped prematurely after randomization of 513 patients in 36 centers to CEA (n = 203), CAS (n = 197), or BMT (n = 113). The one-year rate of the major secondary endpoint did not significantly differ between groups (CEA 2.5%, CAS 3.0%, BMT 0.9%; p = 0.530) as well as rates of any stroke (CEA 3.9%, CAS 4.1%, BMT 0.9%; p = 0.256) and all-cause mortality (CEA 2.5%, CAS 1.0%, BMT 3.5%; p = 0.304). About half of all strokes occurred in the peri-interventional period. Higher albeit statistically non-significant rates of restenosis occurred in the stenting group (CEA 2.0% vs. CAS 5.6%; p = 0.068) without evidence of increased stroke rates. INTERPRETATION: The low sample size of this prematurely stopped trial of 513 patients implies that its power is not sufficient to show that CEA or CAS is superior to a modern medical therapy (BMT) in the primary prevention of ischemic stroke in patients with an asymptomatic carotid stenosis up to one year after treatment. Also, no evidence for differences in safety between CAS and CEA during the first year after treatment could be derived. Follow-up will be performed up to five years. Data may be used for pooled analysis with ongoing trials.
Authors: Leo H Bonati; Stavros Kakkos; Joachim Berkefeld; Gert J de Borst; Richard Bulbulia; Alison Halliday; Isabelle van Herzeele; Igor Koncar; Dominick Jh McCabe; Avtar Lal; Jean-Baptiste Ricco; Peter Ringleb; Martin Taylor-Rowan; Hans-Henning Eckstein Journal: Eur Stroke J Date: 2021-05-11
Authors: Ahmed Abdel Rahim; Mahmoud Ahmed Thabet; Ali Mahmoud Galal; Mohamed Ibrahim Hammoda; Devender Mittapalli Journal: Ann Med Surg (Lond) Date: 2022-06-27
Authors: Xuesong Bai; Yao Feng; Long Li; Kun Yang; Tao Wang; Jichang Luo; Xue Wang; Feng Ling; Yan Ma; Liqun Jiao Journal: BMJ Open Date: 2020-07-05 Impact factor: 2.692
Authors: Alison Halliday; Richard Bulbulia; Leo H Bonati; Johanna Chester; Andrea Cradduck-Bamford; Richard Peto; Hongchao Pan Journal: Lancet Date: 2021-08-29 Impact factor: 79.321
Authors: Francesco Stilo; Nunzio Montelione; Rosalinda Calandrelli; Marisa Distefano; Francesco Spinelli; Vincenzo Di Lazzaro; Fabio Pilato Journal: Ann Transl Med Date: 2020-10