Is stenting equivalent to endarterectomy for asymptomatic carotid stenosis?

The ACST-2 trial1Halliday A Bulbulia R Bonati LH et al.Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy.Lancet. 2021; 398: 1065-1073Google Scholar is the largest randomised trial to date comparing carotid artery stenting (CAS) with carotid endarterectomy (CEA). The study involved 3625 patients with carotid stenosis and no previous or recent same-sided stroke or transient ischaemic attack. However, we feel it is important to counter the investigators’ conclusions that “serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable”.1Halliday A Bulbulia R Bonati LH et al.Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy.Lancet. 2021; 398: 1065-1073Google Scholar First, the peri-procedural period must be experienced by all patients who undergo CEA or CAS. There will always be a rate of serious procedural complications. These complications must be considered when making treatment choices, and not ignored as implied by the terms “competent” or “successful” procedure.1Halliday A Bulbulia R Bonati LH et al.Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy.Lancet. 2021; 398: 1065-1073Google Scholar Unfortunately, all past randomised trials involving patients with asymptomatic carotid stenosis (including ACST-2) were underpowered; trends suggested more peri-procedural and longer-term rates of stroke and peri-procedural death in asymptomatic or recently asymptomatic patients given CAS than in those given CEA, as indicated by 95% CIs overlapping 1. We have summarised the randomised trials of CAS versus CEA with at least 200 patients and a follow-up of at least 12 months that have investigated peri-procedural and longer-term patient outcomes (appendix).1Halliday A Bulbulia R Bonati LH et al.Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy.Lancet. 2021; 398: 1065-1073Google Scholar, 2Brott TG Hobson 2nd, RW Howard G et al.Stenting versus endarterectomy for treatment of carotid-artery stenosis.N Eng J Med. 2010; 363: 11-23Google Scholar, 3Rosenfield K Matsumura JS Chaturvedi S et al.Randomized trial of stent versus surgery for asymptomatic carotid stenosis.N Eng J Med. 2016; 374: 1011-1020Google Scholar There was a trend towards more peri-procedural stroke or death with CAS in ACST-2 (odds ratio [OR] 1·35, 95% CI 0·91–2·03).1Halliday A Bulbulia R Bonati LH et al.Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy.Lancet. 2021; 398: 1065-1073Google Scholar The peri-procedural comparison previously reached statistical significance in a meta-analysis of randomised trials involving patients with asymptomatic carotid stenosis, and is consistent with the increased rate of serious CAS complications in symptomatic patients.4Batchelder AJ Saratzis A Ross Naylor A Overview of primary and secondary analyses from 20 randomised controlled trials comparing carotid artery stenting with carotid endarterectomy.Eur J Vasc Endovasc Surg. 2019; 58: 479-493Google Scholar, 5Abbott AL Brunser AM Giannoukas A et al.Misconceptions regarding the adequacy of best medical intervention alone for asymptomatic carotid stenosis.J Vasc Surg. 2020; 71: 257-269Google Scholar Furthermore, in the ACST-2 trial,1Halliday A Bulbulia R Bonati LH et al.Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy.Lancet. 2021; 398: 1065-1073Google Scholar the 95% CI for the 5-year rate of stroke or peri-procedural death extended to 1·56 (OR 1·23, 95% CI 0·96–1·59). This finding indicates that it is within the realms of probability that CAS would cause up to 1·59 times as many strokes as CEA with a large sample size, as would be the case if the methods from this study were rolled out into routine practice. Such a finding would be clinically significant. Rates of new strokes after CAS and CEA were similar beyond the peri-procedural period in these randomised trials, meaning that rates of peri-procedural stroke largely determined longer-term rates. Therefore, patients who have a procedural stroke from CAS tend to live with that stroke in the long term, and the excess harm caused by CAS is durable. Second, no randomised trial has been adequately powered to compare the peri-procedural rate of the most severe strokes (modified Rankin Scale [mRS] score 3–6). This limitation includes the ACST-2 trial, in which only 13 severe strokes occurred with CAS and 12 with CEA (OR 1·09, 95% CI 0·46–2·61; p=0·84, calculated from published data).1Halliday A Bulbulia R Bonati LH et al.Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy.Lancet. 2021; 398: 1065-1073Google Scholar The 95% CI indicates that, in clinical practice, it is within the realms of probability that CAS would cause up to 2·61 times as many of the most severe strokes as CEA. Again, this finding would be clinically significant. Third, it is inappropriate to infer that less severe strokes (mRS score <3) are not associated with clinically significant disability and to exclude them from treatment decisions. In fact, ACST-2 provides further evidence that rates of serious complications are higher with CAS than with CEA and that these complications are durable. Serious procedural hazards are avoided by not choosing CAS and by properly considering the value of current best medical intervention alone (eg, lifestyle coaching and medication).5Abbott AL Brunser AM Giannoukas A et al.Misconceptions regarding the adequacy of best medical intervention alone for asymptomatic carotid stenosis.J Vasc Surg. 2020; 71: 257-269Google Scholar Medical intervention was a missing therapeutic option in the ACST-2 trial. We declare no competing interests. All authors are members of the Faculty Advocating Collaborative and Thoughtful Carotid Artery Treatments (FACTCATs) with a shared goal of optimising stroke prevention. By design, clinicians and scientists of diverse views are encouraged to be FACTCATs. The views of particular FACTCATs do not necessarily reflect the views of other FACTCATs. Download .pdf (.09 MB) Help with pdf files Supplementary appendix Is stenting equivalent to endarterectomy for asymptomatic carotid stenosis? – Authors’ replyIn the ACST-2 randomised trial1 we compared carotid endarterectomy (CEA) with carotid artery stenting (CAS). The discussion of its findings drew on two other sources of evidence; first, the procedural hazards seen in large population registries, and second, our meta-analysis of all the properly randomised trials. For in comparing these two procedures, the differences in their immediate hazards and the differences in their long-term effects on stroke incidence are both important. Hence, for both these outcomes the treatment differences should be assessed reliably. Full-Text PDF Is stenting equivalent to endarterectomy for asymptomatic carotid stenosis?We read with interest the findings of the ACST-2 trial.1 However, some of the observations made us wonder whether it was accurate to conclude that carotid artery stenting (CAS) and carotid endarterectomy (CEA) were comparable. Full-Text PDF Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomySerious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Full-Text PDF Open Access