Simone J A Donners, Twan J van Velzen, Suk Fun Cheng, John Gregson, Audinga-Dea Hazewinkel, Francesca B Pizzini, Bart J Emmer, Robert Simister, Toby Richards, Philippe A Lyrer, Marina Maurer, Gemma Smith, Gareth Tervit, Laurine van der Steen, Gwynedd E Pickett, Gordon Gubitz, Bob Roozenbeek, Maaike Scheele, John M Bamford, M Eline Kooi, Leo H Bonati
{"title":"优化药物治疗与优化药物治疗加血管重建术治疗无症状或低至中危症状性颈动脉狭窄(ECST-2):一项多中心随机试验的2年中期结果","authors":"Simone J A Donners, Twan J van Velzen, Suk Fun Cheng, John Gregson, Audinga-Dea Hazewinkel, Francesca B Pizzini, Bart J Emmer, Robert Simister, Toby Richards, Philippe A Lyrer, Marina Maurer, Gemma Smith, Gareth Tervit, Laurine van der Steen, Gwynedd E Pickett, Gordon Gubitz, Bob Roozenbeek, Maaike Scheele, John M Bamford, M Eline Kooi, Leo H Bonati","doi":"10.1016/s1474-4422(25)00107-3","DOIUrl":null,"url":null,"abstract":"<h3>Background</h3>Carotid revascularisation, comprising either carotid endarterectomy or stenting, is offered to patients with carotid stenosis to prevent stroke based on the results of randomised trials conducted more than 30 years ago. Since then, medical therapy for stroke prevention has improved. We aimed to assess whether patients with asymptomatic and symptomatic carotid stenosis with a low or intermediate predicted risk of stroke, who received optimised medical therapy (OMT), would benefit from additional revascularisation.<h3>Methods</h3>The Second European Carotid Surgery Trial (ECST-2) is a multicentre randomised trial with blinded outcome adjudication, which was conducted at 30 centres with stroke and carotid revascularisation expertise in Europe and Canada. Patients aged 18 years or older with asymptomatic or symptomatic carotid stenosis of 50% or greater, and a 5-year predicted risk of ipsilateral stroke of less than 20% (estimated using the Carotid Artery Risk [CAR] score), were recruited. Patients were randomly assigned to either OMT alone or OMT plus revascularisation (1:1) using a web-based system. The primary outcome for this 2-year, interim analysis was a hierarchical outcome composite of: (1) periprocedural death, fatal stroke, or fatal myocardial infarction; (2) non-fatal stroke; (3) non-fatal myocardial infarction; or (4) new silent cerebral infarction on imaging. Analysis was by intention-to-treat using the win ratio—ie, each patient in the OMT alone group was compared as a pair with each patient in the OMT plus revascularisation group, with a win declared for the patient with a better outcome within the pair (a tie was declared if neither patient in the pair had a better outcome). The win ratio was calculated as the number of wins in the OMT alone group divided by the number of wins in the OMT plus revascularisation group. This trial is registered with the ISRCTN Registry (ISRCTN97744893) and is ongoing.<h3>Findings</h3>Between March 1, 2012, and Oct 31, 2019, 429 patients were randomly assigned to OMT alone (n=215) or OMT plus revascularisation (n=214). One patient allocated to OMT alone withdrew consent within 48 h and was not considered further. The median age of patients was 72 years (IQR 65–78); 296 (69%) were male and 133 (31%) female. No benefit was recorded in favour of either treatment group with respect to the primary hierarchical outcome assessed 2 years after randomisation, with 5228 (11·4%) wins for the OMT alone group, 5173 (11·3%) wins for the OMT plus revascularisation group, and 35 395 (77·3%) ties between groups (win ratio 1·01 [95% CI 0·60–1·70]; p=0·97). For OMT alone versus OMT plus revascularisation, four versus three patients had periprocedural death, fatal stroke, or fatal myocardial infarction; 11 versus 16 had non-fatal stroke; seven versus five had non-fatal myocardial infarction; and 12 versus seven had new silent cerebral infarction on imaging. One periprocedural death occurred in the OMT plus revascularisation group, which was attributed to decompensated aortic stenosis 1 week after carotid endarterectomy.<h3>Interpretation</h3>No evidence for a benefit of revascularisation in addition to OMT was found in the first 2 years following treatment for patients with asymptomatic or symptomatic carotid stenosis of 50% or greater with a low or intermediate predicted stroke risk (assessed by the CAR score). The results support treating patients with asymptomatic and low or intermediate risk symptomatic carotid stenosis with OMT alone until further data from the 5-year analysis of ECST-2 and other trials become available.<h3>Funding</h3>National Institute for Health and Care Research; Stroke Association; Swiss National Science Foundation; Dutch Organisation for Knowledge and Innovation in Health, Healthcare and Well-Being; Leeds Neurology Foundation.","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"8 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Optimised medical therapy alone versus optimised medical therapy plus revascularisation for asymptomatic or low-to-intermediate risk symptomatic carotid stenosis (ECST-2): 2-year interim results of a multicentre randomised trial\",\"authors\":\"Simone J A Donners, Twan J van Velzen, Suk Fun Cheng, John Gregson, Audinga-Dea Hazewinkel, Francesca B Pizzini, Bart J Emmer, Robert Simister, Toby Richards, Philippe A Lyrer, Marina Maurer, Gemma Smith, Gareth Tervit, Laurine van der Steen, Gwynedd E Pickett, Gordon Gubitz, Bob Roozenbeek, Maaike Scheele, John M Bamford, M Eline Kooi, Leo H Bonati\",\"doi\":\"10.1016/s1474-4422(25)00107-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<h3>Background</h3>Carotid revascularisation, comprising either carotid endarterectomy or stenting, is offered to patients with carotid stenosis to prevent stroke based on the results of randomised trials conducted more than 30 years ago. Since then, medical therapy for stroke prevention has improved. We aimed to assess whether patients with asymptomatic and symptomatic carotid stenosis with a low or intermediate predicted risk of stroke, who received optimised medical therapy (OMT), would benefit from additional revascularisation.<h3>Methods</h3>The Second European Carotid Surgery Trial (ECST-2) is a multicentre randomised trial with blinded outcome adjudication, which was conducted at 30 centres with stroke and carotid revascularisation expertise in Europe and Canada. Patients aged 18 years or older with asymptomatic or symptomatic carotid stenosis of 50% or greater, and a 5-year predicted risk of ipsilateral stroke of less than 20% (estimated using the Carotid Artery Risk [CAR] score), were recruited. Patients were randomly assigned to either OMT alone or OMT plus revascularisation (1:1) using a web-based system. The primary outcome for this 2-year, interim analysis was a hierarchical outcome composite of: (1) periprocedural death, fatal stroke, or fatal myocardial infarction; (2) non-fatal stroke; (3) non-fatal myocardial infarction; or (4) new silent cerebral infarction on imaging. Analysis was by intention-to-treat using the win ratio—ie, each patient in the OMT alone group was compared as a pair with each patient in the OMT plus revascularisation group, with a win declared for the patient with a better outcome within the pair (a tie was declared if neither patient in the pair had a better outcome). The win ratio was calculated as the number of wins in the OMT alone group divided by the number of wins in the OMT plus revascularisation group. This trial is registered with the ISRCTN Registry (ISRCTN97744893) and is ongoing.<h3>Findings</h3>Between March 1, 2012, and Oct 31, 2019, 429 patients were randomly assigned to OMT alone (n=215) or OMT plus revascularisation (n=214). One patient allocated to OMT alone withdrew consent within 48 h and was not considered further. The median age of patients was 72 years (IQR 65–78); 296 (69%) were male and 133 (31%) female. No benefit was recorded in favour of either treatment group with respect to the primary hierarchical outcome assessed 2 years after randomisation, with 5228 (11·4%) wins for the OMT alone group, 5173 (11·3%) wins for the OMT plus revascularisation group, and 35 395 (77·3%) ties between groups (win ratio 1·01 [95% CI 0·60–1·70]; p=0·97). For OMT alone versus OMT plus revascularisation, four versus three patients had periprocedural death, fatal stroke, or fatal myocardial infarction; 11 versus 16 had non-fatal stroke; seven versus five had non-fatal myocardial infarction; and 12 versus seven had new silent cerebral infarction on imaging. 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引用次数: 0
摘要
背景:根据30多年前进行的随机试验结果,颈动脉血管重建术,包括颈动脉内膜切除术或支架植入术,被提供给颈动脉狭窄患者以预防卒中。从那时起,预防中风的医学治疗得到了改善。我们的目的是评估无症状和有症状的颈动脉狭窄患者,卒中预测风险低或中等,接受优化药物治疗(OMT),是否会从额外的血运重建中获益。第二项欧洲颈动脉手术试验(ECST-2)是一项多中心随机试验,采用盲法结果评判,在欧洲和加拿大的30个卒中和颈动脉血运重建专业中心进行。招募年龄在18岁或以上,无症状或有症状的颈动脉狭窄50%或以上,5年预测同侧卒中风险小于20%(使用颈动脉风险[CAR]评分估计)的患者。使用基于网络的系统,患者被随机分配到单独的OMT或OMT加血运重建术(1:1)。这项为期2年的中期分析的主要结局是分层结局组合:(1)围手术期死亡、致死性卒中或致死性心肌梗死;(2)非致死性中风;(3)非致死性心肌梗死;或(4)影像学上新发无症状脑梗死。分析采用意向治疗比,即,将OMT单独组的每位患者与OMT加血运重建术组的每位患者作为一对进行比较,并宣布在这对患者中结果较好的患者获胜(如果这对患者中都没有较好的结果则宣布平局)。胜率计算为单纯OMT组的胜利数除以OMT加血运重建组的胜利数。该试验已在ISRCTN注册中心注册(ISRCTN97744893),并正在进行中。在2012年3月1日至2019年10月31日期间,429名患者被随机分配到OMT单独治疗组(n=215)或OMT加血运重建术组(n=214)。一名单独分配到OMT的患者在48小时内撤回了同意,没有进一步考虑。患者中位年龄为72岁(IQR 65-78);其中男性296人(69%),女性133人(31%)。在随机化2年后评估的主要分级结果中,没有记录到任何一个治疗组的获益,单独OMT组有5228个(11.4%)的胜利,OMT加血运重建术组有5173个(11.3%)的胜利,两组之间有35395个(77.3%)的平局(胜比1.01 [95% CI 0.60 - 1.70];p = 0·97)。单独OMT与OMT加血运重建术相比,4例与3例患者发生围手术期死亡、致命性卒中或致命性心肌梗死;11人非致命性中风,16人非致命性中风;非致死性心肌梗死7例vs 5例;12对7在影像学上有新的无症状脑梗死。OMT加血运重建术组发生一例围手术期死亡,原因是颈动脉内膜切除术后1周出现代偿性主动脉狭窄。解释:对于无症状或症状性颈动脉狭窄50%或以上且预测卒中风险低或中等(由CAR评分评估)的患者,在治疗后的前2年,没有发现除OMT外血管重建的益处。研究结果支持仅使用OMT治疗无症状和低或中危症状性颈动脉狭窄患者,直到从ECST-2和其他试验的5年分析获得进一步数据。国家卫生和保健研究所;中风协会;瑞士国家科学基金会;荷兰卫生、保健和福利知识和创新组织;利兹神经病学基金会。
Optimised medical therapy alone versus optimised medical therapy plus revascularisation for asymptomatic or low-to-intermediate risk symptomatic carotid stenosis (ECST-2): 2-year interim results of a multicentre randomised trial
Background
Carotid revascularisation, comprising either carotid endarterectomy or stenting, is offered to patients with carotid stenosis to prevent stroke based on the results of randomised trials conducted more than 30 years ago. Since then, medical therapy for stroke prevention has improved. We aimed to assess whether patients with asymptomatic and symptomatic carotid stenosis with a low or intermediate predicted risk of stroke, who received optimised medical therapy (OMT), would benefit from additional revascularisation.
Methods
The Second European Carotid Surgery Trial (ECST-2) is a multicentre randomised trial with blinded outcome adjudication, which was conducted at 30 centres with stroke and carotid revascularisation expertise in Europe and Canada. Patients aged 18 years or older with asymptomatic or symptomatic carotid stenosis of 50% or greater, and a 5-year predicted risk of ipsilateral stroke of less than 20% (estimated using the Carotid Artery Risk [CAR] score), were recruited. Patients were randomly assigned to either OMT alone or OMT plus revascularisation (1:1) using a web-based system. The primary outcome for this 2-year, interim analysis was a hierarchical outcome composite of: (1) periprocedural death, fatal stroke, or fatal myocardial infarction; (2) non-fatal stroke; (3) non-fatal myocardial infarction; or (4) new silent cerebral infarction on imaging. Analysis was by intention-to-treat using the win ratio—ie, each patient in the OMT alone group was compared as a pair with each patient in the OMT plus revascularisation group, with a win declared for the patient with a better outcome within the pair (a tie was declared if neither patient in the pair had a better outcome). The win ratio was calculated as the number of wins in the OMT alone group divided by the number of wins in the OMT plus revascularisation group. This trial is registered with the ISRCTN Registry (ISRCTN97744893) and is ongoing.
Findings
Between March 1, 2012, and Oct 31, 2019, 429 patients were randomly assigned to OMT alone (n=215) or OMT plus revascularisation (n=214). One patient allocated to OMT alone withdrew consent within 48 h and was not considered further. The median age of patients was 72 years (IQR 65–78); 296 (69%) were male and 133 (31%) female. No benefit was recorded in favour of either treatment group with respect to the primary hierarchical outcome assessed 2 years after randomisation, with 5228 (11·4%) wins for the OMT alone group, 5173 (11·3%) wins for the OMT plus revascularisation group, and 35 395 (77·3%) ties between groups (win ratio 1·01 [95% CI 0·60–1·70]; p=0·97). For OMT alone versus OMT plus revascularisation, four versus three patients had periprocedural death, fatal stroke, or fatal myocardial infarction; 11 versus 16 had non-fatal stroke; seven versus five had non-fatal myocardial infarction; and 12 versus seven had new silent cerebral infarction on imaging. One periprocedural death occurred in the OMT plus revascularisation group, which was attributed to decompensated aortic stenosis 1 week after carotid endarterectomy.
Interpretation
No evidence for a benefit of revascularisation in addition to OMT was found in the first 2 years following treatment for patients with asymptomatic or symptomatic carotid stenosis of 50% or greater with a low or intermediate predicted stroke risk (assessed by the CAR score). The results support treating patients with asymptomatic and low or intermediate risk symptomatic carotid stenosis with OMT alone until further data from the 5-year analysis of ECST-2 and other trials become available.
Funding
National Institute for Health and Care Research; Stroke Association; Swiss National Science Foundation; Dutch Organisation for Knowledge and Innovation in Health, Healthcare and Well-Being; Leeds Neurology Foundation.