The optimal management for asymptomatic carotid stenosis remains a key question, particularly with advancements in medical therapy. The CREST-2 trials aimed to determine if adding revascularization to intensive medical management provides greater benefit than medical management alone in this patient population.²

Two parallel, observer-blinded clinical trials (CREST-2; NCT02089217) were conducted across 155 centres in five countries, enrolling patients with high-grade (≥70%) asymptomatic carotid stenosis.¹

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.

In the stenting trial, the 4-year incidence of primary outcome events was significantly lower in the stenting group at 2.8% (95% CI, 1.5 to 4.3) compared to 6.0% (95% CI, 3.8 to 8.3) in the medical-therapy group (P=0.02). 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. The rate was 3.7% (95% CI, 2.1 to 5.5) in the endarterectomy group versus 5.3% (95% CI, 3.3 to 7.4) in the medical-therapy group (P=0.24). In the perioperative period, nine strokes occurred in the endarterectomy group compared to three strokes in the medical-therapy group.

The findings suggest a divergence in outcomes depending on the revascularization method. The CREST-2 Investigators concluded that '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 These results highlight the importance of considering the specific revascularization strategy alongside intensive medical therapy for patients with asymptomatic carotid stenosis.

References

1. Brott TG, Howard G, Lal BK, et al. Medical Management and Revascularization for Asymptomatic Carotid Stenosis. N Engl J Med. 2025. https://doi.org/10.1056/NEJMoa2508800.

2. Brown MM, Bonati LH. Managing Asymptomatic Carotid Stenosis. N Engl J Med. 2025. https://doi.org/10.1056/NEJMe2515725.

This study was funded by the National Institute of Neurological Disorders and Stroke, the Centers for Medicare and Medicaid Services, and NIH StrokeNet.

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