The optimal management for patients with high-grade asymptomatic carotid stenosis remains a key clinical question, particularly with advancements in medical therapy and revascularisation techniques. The CREST-2 trials were designed to assess whether adding revascularisation to intensive medical management provides a greater benefit than intensive medical management alone in this patient population.¹

Methodology

CREST-2 consisted of two parallel, observer-blinded clinical trials conducted across 155 centres in five countries. The trials enrolled patients with high-grade (≥70%) asymptomatic carotid stenosis.

• The stenting trial randomised 1,245 patients to either intensive medical management alone or carotid-artery stenting plus intensive medical management.
• The endarterectomy trial randomised 1,240 patients to either intensive medical management alone or carotid endarterectomy plus intensive medical management.

The primary outcome for both trials was a composite of any stroke or death from randomisation to 44 days, or ipsilateral ischaemic stroke during the remaining follow-up period of up to 4 years.

Results

In the stenting trial, the 4-year incidence of primary outcome events was significantly lower in the stenting group compared to the medical-therapy group (2.8% vs 6.0%; P=0.02 for the absolute difference). During the initial 44-day perioperative period, no strokes or deaths occurred in the medical-therapy group, while seven strokes and one death occurred in the stenting group.

In the endarterectomy trial, the difference in the 4-year incidence of primary outcome events was not statistically significant between the endarterectomy group and the medical-therapy group (3.7% vs 5.3%; P=0.24 for the absolute difference). In the first 44 days, three strokes occurred in the medical-therapy group, compared to nine strokes in the endarterectomy group.

In Practice

The findings from CREST-2 suggest different outcomes depending on the revascularisation method used in conjunction with intensive medical therapy for asymptomatic carotid stenosis. The addition of stenting resulted in a lower risk of the primary composite outcome over 4 years, despite a higher initial risk of perioperative events. Conversely, the addition of carotid endarterectomy did not demonstrate a significant benefit over medical management alone.²

As summarised by the CREST-2 Investigators, “Among patients with high-grade stenosis without recent symptoms, the addition of stenting led to a lower risk of a composite of perioperative stroke or death or ipsilateral stroke within 4 years than intensive medical management alone. Carotid endarterectomy did not lead to a significant benefit.”¹

This study was funded by the National Institute of Neurological Disorders and Stroke, National Institutes of Health (NIH), and the Centers for Medicare and Medicaid Services, Department of Health and Human Services.

References

1. Brott TG, Howard G, Lal BK, et al. Medical Management and Revascularization for Asymptomatic Carotid Stenosis. N Engl J Med 2026;394:219-231. https://doi.org/10.1056/NEJMoa2508800

2. Brown MM, Bonati LH. Managing Asymptomatic Carotid Stenosis. N Engl J Med 2025;394(3):296-297. https://doi.org/10.1056/NEJMe2515725

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