ACST-2: Largest trial to date comparing carotid artery stenting to carotid endarterectomy finds no difference in disabling stroke at 5 years.

Key Points:

• Carotid artery stenting and carotid endarterectomy have both been employed to treat severely stenosed carotid arteries, a known risk factor for disabling stroke.
• In ACST-2, patient with severe carotid artery stenosis were randomized in a 1:1 fashion to receive either carotid artery stenting or carotid endarterectomy.
• Serious complications from either procedure were comparably rare. At 5 years, the nonprocedural stroke rate was 2.5% for both carotid artery stenting and endarterectomy.

While carotid artery stenosis is a known risk factor for disabling stroke, a general consensus on the appropriate treatment modality has not been established. Both carotid artery stenting (CAS) and carotid endarterectomy (CEA) are widely employed. To date, however, the procedural risks, and long- term stroke prevention, of the two treatments have not been comparatively studied. The second Asymptomatic Carotid Surgery Trial (ACST-2) sought to answer just that. In a Hot Line Session at the 2021 European Society of Cardiology Congress today, Dr. Alison Halliday (Oxford University, London) presented the long awaited 5-year outcomes from the study.

ACS-2 is a prospective, multicenter, international, randomized control trial that enrolled participants from 130 sites in 33 countries. Patients with asymptomatic carotid artery stenosis (>60% by ultrasound) and no history of stroke or transient ischemic attack were randomized in a 1:1 fashion to carotid artery stenting or carotid endarterectomy.  A total of 3,625 participants were enrolled. The main outcomes of interest were (a) procedural risks: morbidity and mortality within one month of the procedure and (b) non-procedural disabling and nondisabling stroke.

Participants were mostly male (70%) with a median age of 70 years. Most were on an antiplatelet therapy at the time of entry (>90%) as well as a lipid lowering agent (>84%).

Procedural risks were similar in both groups, with 1% of participants in either arm suffering from stroke or death within 30 days, and 2% in either arm suffering from a nondisabling stroke. At five years, the rate of fatal or disabling stroke was 2.5% in the CAS group and 2.5% in the CEA group, representing a rate ratio of 0.98 (95% confidence interval [CI]0.64–1.48; p=0.91). The rate of non-disabling stroke was numerically higher in the CAS group (5.3% vs 4.5% [RR 1.16; 95% CI 0.86–1.57; p=0.33]) but did not meet statistical significance.

The authors then took the results of this trial, which is the largest head-to-head comparison of asymptomatic patients with carotid stenosis to date, and combined them with prior trials (CREST, SPACE-2, and ACST-1) for a metanalysis. When comparing CAS to CEA in this manner, there was similarly no significant difference between the two (RR 1.16; 95% CI 0.86–1.57; p=0.33).

When discussing the results of the trial today, Dr. Halliday was asked about adding a third arm of patients who underwent conservative management with medical therapy. “The patients enrolled in this trial already had a decision made that revascularization should occur,” she replied, “a large proportion of patients were already on optimal medical therapy, and the benefit of revascularization was thus additive.”

The trial results were simultaneously published in the Lancet.