Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy.

BACKGROUND: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. METHODS: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. FINDINGS: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86-1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91-1·32; p=0·21). INTERPRETATION: 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. FUNDING: UK Medical Research Council and Health Technology Assessment Programme.

Editor's Choice - Risk of Stroke before Revascularisation in Patients with Symptomatic Carotid Stenosis: A Pooled Analysis of Randomised Controlled Trials.

OBJECTIVE: Current guidelines recommending rapid revascularisation of symptomatic carotid stenosis are largely based on data from clinical trials performed at a time when best medical therapy was potentially less effective than today. The risk of stroke and its predictors among patients with symptomatic carotid stenosis awaiting revascularisation in recent randomised controlled trials (RCTs) and in medical arms of earlier RCTs was assessed. METHODS: The pooled data of individual patients with symptomatic carotid stenosis randomised to stenting (CAS) or endarterectomy (CEA) in four recent RCTs, and of patients randomised to medical therapy in three earlier RCTs comparing CEA vs. medical therapy, were compared. The primary outcome event was any stroke occurring between randomisation and treatment by CAS or CEA, or within 120 days after randomisation. RESULTS: A total of 4 754 patients from recent trials and 1 227 from earlier trials were included. In recent trials, patients were randomised a median of 18 (IQR 7, 50) days after the qualifying event (QE). Twenty-three suffered a stroke while waiting for revascularisation (cumulative 120 day risk 1.97%, 95% confidence interval [CI] 0.75 - 3.17). Shorter time from QE until randomisation increased stroke risk after randomisation (χ2 = 6.58, p = .011). Sixty-one patients had a stroke within 120 days of randomisation in the medical arms of earlier trials (cumulative risk 5%, 95% CI 3.8 - 6.2). Stroke risk was lower in recent than earlier trials when adjusted for time between QE and randomisation, age, severity of QE, and degree of carotid stenosis (HR 0.47, 95% CI 0.25 - 0.88, p = .019). CONCLUSION: Patients with symptomatic carotid stenosis enrolled in recent large RCTs had a lower risk of stroke after randomisation than historical controls. The added benefit of carotid revascularisation to modern medical care needs to be revisited in future studies. Until then, adhering to current recommendations for early revascularisation of patients with symptomatic carotid stenosis considered to require invasive treatment is advisable.

Improving Quality of Carotid Interventions: Identifying Hospital-Level Structural Factors that can Improve Outcomes.

BACKGROUND: "Structural factors" relating to organization of hospitals may affect procedural outcomes. This study's aim was to clarify associations between structural factors and outcomes after carotid endarterectomy (CEA) and carotid endarterectomy stenting (CAS). METHODS: A systematic review of studies published in English since 2005 was conducted. Structural factors assessed were as follows: population size served by the vascular department; number of hospital beds; availability of dedicated vascular beds; established clinical pathways; surgical intensive care unit (SICU) size; and specialty of surgeon/interventionalist. Primary outcomes were as follows: mortality; stroke; cardiac complications; length of hospital stay (LOS); and cost. RESULTS: There were 11 studies (n = 95,100 patients) included in this systematic review. For CEA, reduced mortality (P < 0.0001) and stroke rates (P = 0.001) were associated with vascular departments serving >75,000 people. Larger hospitals were associated with lower mortality, stroke rate, and cardiac events, compared with smaller hospitals (less than 130 beds). Provision of vascular beds after CEA was associated with lower mortality (P = 0.0008) and fewer cardiac events (P = 0.03). Adherence to established clinical pathways was associated with reduced stroke and cardiac event rates while reducing CEA costs. Large SICUs (≥7 beds) and dedicated intensivists were associated with decreased mortality after CEA while a large SICU was associated with reduced stroke rate (P = 0.001). Vascular surgeons performing CEA were associated with lower stroke rates and shorter LOS (P = 0.0001) than other specialists. CAS outcomes were not influenced by specialty but costless when performed by vascular surgeons (P < 0.0001). CONCLUSIONS: Structural factors affect CEA outcomes, but data on CAS were limited. These findings may inform reconfiguration of vascular services, reducing risks and costs associated with carotid interventions.

The Asymptomatic Carotid Surgery Trial-2 (ACST-2): an ongoing randomised controlled trial comparing carotid endarterectomy with carotid artery stenting to prevent stroke.

BACKGROUND: A successful open surgical operation to remove atheromatous carotid artery narrowing that has not yet caused a stroke (asymptomatic carotid stenosis) carries some procedural risk but, if completed successfully, halves patients' future annual stroke risk for at least 10 years. A newer, less invasive alternative is carotid stenting, which also carries some procedural risk, especially if the carotid lesion has recently given rise to a stroke (symptomatic carotid stenosis). For both surgery and stenting, improvements in technique (and in medication) have reduced risk. Early studies showed that treating carotid narrowing by stenting, particularly for symptomatic lesions, caused more procedural minor strokes than surgery, but more recent trials in symptomatic and in asymptomatic patients found that both procedures might now be equally safe and effective. However, low patient numbers, short follow-up of the long-term effects on stroke rates and wide confidence intervals mean that worldwide uncertainty persists between carotid surgery and carotid stenting, and national and international guidelines remain unclear as to which is generally better. OBJECTIVES: The second Asymptomatic Carotid Surgery Trial (ACST-2) compares carotid endarterectomy (CEA) with carotid artery stenting (CAS) directly, randomising patients with asymptomatic carotid stenosis for whom a carotid procedure is considered definitely necessary; both procedures seem anatomically feasible, and there is substantial uncertainty as to which of the two would be better for such individuals. Although it will compare procedural risks, the trial's primary aim is to compare the long-term durability of protection against strokes occurring in the years post procedure due to any remaining or recurrent carotid disease. DESIGN: Randomised controlled trial comparing CEA with CAS. SETTING: Hospitals in the UK and worldwide, in which carotid procedures are common. PARTICIPANTS: Men and women with severely stenotic atherosclerotic carotid artery disease, with or without previous stroke but with no recent symptoms from the randomised artery. INTERVENTIONS: CEA and CAS. OUTCOMES: (1) Periprocedural risk defined as myocardial infarction, stroke or death within 30 days after the randomised procedure and (2) long-term rates of disabling or fatal stroke during follow-up of patients. MEASUREMENT OF COSTS AND OUTCOMES: Measurement of intervention costs and stroke costs (periprocedural and during follow-up) and of quality of life [EuroQol-5 Dimensions (EQ-5D®)] for patients in the top six recruiting countries (UK, Italy, Belgium, Germany, Serbia and Sweden), who currently constitute 85% of those randomised. PROGRESS SO FAR: By the end of March 2016, ACST-2 had included 2125 patients, nearly two-thirds of the planned recruitment of 3600; 1061 were randomly allocated to CEA and 1064 to CAS. CONCLUSIONS: Further funding has been secured and recruitment continues, with completion anticipated by the end of 2019. ACST-2 will report initial results in 2021. TRIAL REGISTRATION: Current Controlled Trials ISRCTN21144362. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 57. See the NIHR Journals Library website for further project information. Funding was also received from BUPA Foundation [BUPAF/33(a)/05].