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Randomized trials from decades ago showed that patients with asymptomatic carotid stenosis could benefit from endarterectomy in the long run if they would accept early risks for perioperative stroke. But medical therapy has improved, and a more contemporary, international, randomized trial — CREST-2 — was launched in 2014 to revisit this issue (see ). The long-awaited results now have been published.
Patients with asymptomatic carotid stenosis (≥70%) were recruited through publicity at study centers and their surrounding communities; most participants had hypertension and hyperlipidemia, and half had noncarotid cardiovascular disease. About 1250 were randomized to endarterectomy or no endarterectomy, and in a parallel study, an additional 1250 participants were randomized to stenting or no stenting. All patients received intensive medical management. The composite outcome included both any stroke or death during the 6 weeks after enrollment (to capture periprocedural events) and ipsilateral ischemic stroke after 6 weeks.
During 4 years of follow-up, researchers noted no significant difference in the composite outcome between the endarterectomy and no-endarterectomy groups (3.7% and 5.3%; P=0.24).
A difference in the 4-year composite outcome between the stenting and no-stenting groups was significant (2.8% vs. 6.0%; P=0.02), but certain details are worth mentioning:
Among ≈600 patients in each group, stented patients had 8 events (1 death, 5 nondisabling strokes, and 2 disabling strokes) during the initial 6-week period, whereas nonstented patients had no events.
The 3 percentage-point difference in the composite outcome at 4 years was driven by an excess of 20 nondisabling strokes in the nonstented group, with no difference in disabling strokes.
Brott TG, et al. Medical management and revascularization for asymptomatic carotid stenosis. N Engl J Med 2025 Nov 21; [e-pub]. DOI: 10.1056/NEJMoa2508800.
Brown MM, Bonati LH. Managing asymptomatic carotid stenosis. N Engl J Med 2025 Nov 21; [e-pub]. DOI: 10.1056/NEJMe2515725.
Comment
This study essentially showed that, for every 100 patients, stenting prevented 3 nondisabling strokes at 4 years but caused 1 periprocedural stroke. The results likely reflect the best possible procedural outcomes: To participate in the trial, interventionalists had to demonstrate low complication rates for their previous procedures.
In real-world practice, asymptomatic stenosis is discovered in various ways — for example, when patients with vague nonstroke neurological symptoms undergo carotid ultrasound inappropriately, or when patients are screened in physicians’ offices or by private companies in the community. Outcomes of medical management versus revascularization might differ among these various patient populations in ways that aren’t predictable. Notably, in 2021, the U.S. Preventive Services Task Force recommended against screening; in my view, CREST-2 doesn’t provide sufficient justification to change that recommendation.
Editorialists conclude that most patients with asymptomatic carotid stenosis should begin intensive medical therapy, and that revascularization should be reserved for the small proportion of patients who develop symptoms. I find that conclusion to be reasonable.