Insights From the Two Largest Trials on Asymptomatic Carotid Stenosis

The two Asymptomatic Carotid Surgery Trials (ACST-1 and ACST-2) are the largest trials of carotid interventions to date and have shed valuable light on treatment for asymptomatic carotid stenosis. Lessons learned from these two trials were presented on Monday afternoon at LINC 2022 by ASCT-2 co-principal investigator Richard Bulbulia, a consultant vascular surgeon at Gloucestershire Royal Hospital and research fellow at the Clinical Trial Service Unit, Oxford University, UK.

In his presentation, Dr Bulbulia discussed ACST-1, which compared immediate carotid surgery plus medical therapy to medical therapy alone, and ACST-2, which compared carotid endarterectomy to carotid artery stenting. “ACST-1, which was led by my colleague Alison Halliday, was the largest ever trial of a vascular surgical procedure at the time, enrolling over 3,000 patients with a tight asymptomatic carotid stenosis,” he summarized. “It showed that successful carotid surgery halved the long-term risk of stroke at 5 years, and these benefits were maintained to 10 years.”

The ACST-1 results indicate a definite benefit of carotid surgery compared to medical therapy alone; however, there has been some debate in the literature as to the continuing applicability of these results given improvements in medical therapy both during and after the trial. Commenting on this controversy, Dr Bulbulia acknowledged these concerns and the importance of ongoing research, but concluded that the benefits of carotid intervention are still likely to be significant.

“As regards medical improvements during the trial, it is true that aspirin and antihypertensive therapies were widely used throughout, while the use of statins was quite uncommon at the start of the trial, becoming more common in later years. However, the results showed that even in patients taking good triple medical therapy including statins, successful carotid surgery halved the residual stroke risk,” he observed.

“Since the 10-year outcomes of ACST-1 were published, we have seen further improvements in medical therapy, specifically in more intensive lipid-lowering therapies,” he continued. “The ongoing CREST-2 and ACTRIS trials are looking at the role of carotid intervention versus really intensive goal-directed risk factor modification in asymptomatic patients. Results will emerge in several years, but it remains probable that significant numbers of patients will require and benefit from selective carotid intervention.”.

The ACST-2 results indicate that, following a successful procedure, both carotid surgery and carotid stenting provide similarly good durable protection against stroke. "This allows doctors and patients to decide which treatment is preferable for an individual patient, based on anatomy, anesthetic risk, and patient preference,” Dr. Bulbulia said. “It’s always good to have more than one way of treating a problem!”

After outlining the clinical lessons gained from ACST-1 and ACST-2, Dr Bulbulia shared his insights on the practicalities of designing and conducting large trials. Both ACST studies enrolled over 3,000 patients, and therefore involved considerable attention to trial design and logistics.

“You first need to ask an important question, then answer it reliably. This involves reducing bias by randomisation, and minimising the risk of ‘chance’ findings by recruiting large numbers of patients,” Dr Bulbulia advised. “Because trials need to be big, they must be simple, creating the least possible work for busy clinicians who we depend on entirely for recruitment.”

Dr Bulbulia closed by considering the future of research in this field. “While carotid disease is one of the most thoroughly studied areas in vascular surgery, many questions remain unanswered, and things that we previously thought we knew have become less clear with advances in medical therapies, stent design and cerebral protection,” he commented.

“CREST-2, ACTRIS, and ECST-2 will help clarify the role of surgery and stenting in asymptomatic patients, and I’d encourage clinicians to randomise patients to these studies if they can. But I am also really interested in the role of stenting in symptomatic carotid disease, as carotid stenting has evolved substantially since the last trials of carotid endarterectomy versus stenting were completed in this patient population. We need another trial!”