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

Abstract

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.

Figure 1

Trial profile CAS=carotid artery stenting. CEA=carotid endarterectomy.

Figure 2

Kaplan-Meier estimates of 5-year outcomes among asymptomatic patients randomly allocated to CAS versus CEA CAS=carotid artery stenting. CEA=carotid endarterectomy. *Last rate is after year 5 (and all three procedural strokes due to a second carotid procedure were after year 5).

Figure 3

Subgroup analyses of long-term non-procedural stroke rates, by random allocation to CAS or to CEA 2p=two-sided p value. CAS=carotid artery stenting. CEA=carotid endarterectomy. ITT=intention-to-treat. O–E=log-rank observed minus expected. RR=rate ratio.

Figure 4

Trials of CAS versus CEA for asymptomatic or symptomatic carotid stenosis—ITT analyses of non-procedural strokes (ipsilateral ischaemic stroke plus other strokes) The figure excludes the 13 smaller trials (all evenly randomised) identified by the 2020 Cochrane review, which reported that they had, in total, 30 non-procedural strokes in 692 patients with CAS versus 24 non-procedural strokes in 715 patients with CEA. A repeat search on July 31, 2021, re-using the Cochrane search criteria identified no more trials of CAS versus CEA. 2p=two-sided p value. CAS=carotid artery stenting. CEA=carotid endarterectomy. ITT=intention-to-treat. O–E=log-rank observed minus expected. Var (O–E)=variance of (O–E). *ACT-1 allocated patients in a 3:1 ratio; for balance, therefore, it contributes two thirds of its CAS cases and double its CEA cases to the subtotal and the total case numbers; its main report provides exact numbers only for ischaemic strokes within 1 year.