Stenting Outperforms Endarterectomy but Offers Only Modest Benefit in Asymptomatic Carotid Stenosis: CREST-2 trial

Asymptomatic carotid stenosis of ≥70% has conventionally been treated with revascularization for the purpose of preventing a future ischemic stroke. However, baseline outcomes have dramatically improved due to the evolution of intensive medical management that includes antiplatelet therapy, lipid-lowering agents, and aggressive risk factor modification, thus raising questions about the value added by invasive procedures. The present investigation evaluated whether adding carotid-artery stenting or carotid endarterectomy to optimized medical therapy conferred superior protection against stroke and death compared with medical therapy alone in patients without recent neurological symptoms.

Two parallel, observer-blinded clinical trials across 155 centers in five countries were conducted. Patients with high-grade asymptomatic carotid stenosis (≥70%) were enrolled and then randomly assigned to either intensive medical therapy alone or intensive medical therapy plus revascularization. The stenting trial randomly assigned 1245 patients to either medical therapy alone or carotid-artery stenting plus medical therapy, whereas the endarterectomy trial randomly assigned 1240 patients to medical therapy alone or carotid endarterectomy plus medical therapy. The primary outcome was a composite of any stroke or death from randomization to 44 days or ipsilateral ischemic stroke during the remaining follow-up period, extending to 4 years.

Results

• In the stenting trial, the 4-year incidence of the primary composite outcome was 6.0% (95% CI, 3.8 to 8.3) in the medical-therapy group and 2.8% (95% CI, 1.5 to 4.3) in the stenting group, reflecting a statistically significant reduction with stenting (P=0.02 for the absolute difference).

• This indicated a clear benefit for adding stenting to intensive medical management for long-term stroke prevention.

• By comparison, in the endarterectomy trial, the 4-year incidence of primary outcomes was 5.3% (95% CI, 3.3 to 7.4) in the medical-therapy group and 3.7% (95% CI, 2.1 to 5.5) in the endarterectomy group, without a statistically significant difference (P=0.24 for the absolute difference).

• The stenting trial reported no strokes or deaths during the early perioperative period (day 0 to 44) in the medical-therapy group, compared with seven strokes and one death in the stenting group.

• During the same early perioperative period, the endarterectomy trial reported three strokes in the medical-therapy group and nine strokes in the endarterectomy group, emphasizing an early procedural risk of surgical intervention.

In patients with high-grade asymptomatic carotid stenosis, the addition of carotid-artery stenting to intensive medical management significantly lowered the risk of perioperative stroke, death, or ipsilateral ischemic stroke over 4 years, whereas carotid endarterectomy did not exhibit a significant benefit. These findings support a more selective and evidence-based approach to revascularization, focusing on intensive medical therapy with stenting reserved for properly selected patients.

Reference:

Brott, T. G., Howard, G., Lal, B. K., Voeks, J. H., Turan, T. N., Roubin, G. S., Lazar, R. M., Brown, R. D., Jr, Huston, J., 3rd, Edwards, L. J., Jones, M., Clark, W. M., Chamorro, Á., Llull, L., Mena-Hurtado, C., Heck, D., Marshall, R. S., Howard, V. J., Moore, W. S., … CREST-2 Investigators. (2025). Medical management and revascularization for asymptomatic carotid stenosis. The New England Journal of Medicine, NEJMoa2508800. https://doi.org/10.1056/NEJMoa2508800