A major international study led by Mayo Clinic researchers and funded by the National Institutes of Health found that for people with severe carotid artery narrowing who haven’t experienced recent stroke symptoms, carotid artery stenting, combined with intensive medical therapy, significantly lowered stroke risk compared with medical therapy alone.
Traditional surgery (carotid endarterectomy) did not show the same benefit, according to the research, which was published in The New England Journal of Medicine.
The Carotid Revascularisation and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST-2) is the largest study to date comparing current treatment approaches for this condition, caused by plaque build-up in the arteries supplying blood to the brain.
Carotid stenosis can lead to a stroke if plaque breaks off and blocks blood flow. Although surgery and stenting have long been used to open these arteries, newer medications and better risk factor control have raised questions about whether these procedures are still needed for people who don’t have symptoms.
“Decades ago, surgery clearly helped prevent strokes in many patients,” said Thomas Brott, MD, a neurologist at Mayo Clinic in Florida and the study’s senior author. "But medical therapy has improved so much that we needed to re-examine the balance between benefit and risk for people who have no symptoms.”
The CREST-2 programme consisted of two parallel, randomised clinical trials at 155 medical centres in five countries: Australia, Canada, Israel, Spain and the US. Each enrolled more than 1 200 adults with severe carotid artery narrowing of 70% or greater who had not had a stroke or transient ischaemic attack (mini-stroke) in the past six months.
In one trial, participants received stenting plus intensive medical therapy or medical therapy alone. In the other, participants received endarterectomy plus medical therapy or medical therapy alone.
All of them received comprehensive medical care, including lifestyle coaching and medication as needed, to manage their blood pressure, low-density lipoprotein (LDL) cholesterol and diabetes, and to help them stop smoking.
Working with investigators from the University of Alabama at Birmingham, researchers analysed the occurrence of stroke and death within 44 days of stenting or surgery. They also analysed the occurrence of stroke over four years on the same side of the body as the narrowed artery.
The stenting trial found a significant reduction in stroke: over four years, 2.8% of patients treated with stenting and medical therapy had a stroke, compared with 6% of those on medical therapy alone (roughly half the risk of stroke).
However, in the endarterectomy trial, the difference in stroke rates (3.7% with surgery vs. 5.3% with medical therapy alone) was not statistically significant. Serious complications were uncommon with either procedure.
The findings provide clearer guidance for physicians and patients considering a preventive procedure.
Brott emphasises personalised decision-making.
“For some patients, particularly those with more advanced narrowing or plaque that appears unstable or more likely to cause a blockage, stenting may offer added protection, while for others, medical therapy alone may be enough,” he said.
Close follow-up and co-ordinated care helped all participants achieve and maintain significant improvements in their blood pressure and cholesterol levels.
Researchers will continue to track participants for long-term results. They are also studying whether imaging tools can help identify which patients benefit most from each treatment.
Study details
Medical Management and Revascularisation for Asymptomatic Carotid Stenosis
Thomas Brott, George Howard, Brajesh Lal, Jenifer Voeks, Tanya Turan et al for the CREST-2 Investigators
Published in The New England Medical Journal on 21 November 2025
Abstract
Background
Improvements in medical therapy, carotid-artery stenting, and carotid endarterectomy call into question the preferred management of asymptomatic carotid stenosis. Whether adding revascularisation to intensive medical management would provide greater benefit than intensive medical management alone is unclear.
Methods
We conducted two parallel, observer-blinded clinical trials that enrolled patients with high-grade (≥70%) asymptomatic carotid stenosis across 155 centres in five countries. The stenting trial compared intensive medical management alone (medical-therapy group) with carotid-artery stenting plus intensive medical management (stenting group); the endarterectomy trial compared intensive medical management alone (medical-therapy group) with carotid endarterectomy plus intensive medical management (endarterectomy group). The primary outcome was a composite of any stroke or death, assessed from randomisation to 44 days, or ipsilateral ischaemic stroke, assessed during the remaining follow-up period up to four years.
Results
A total of 1245 patients underwent randomisation in the stenting trial and 1240 in the endarterectomy trial. In the stenting trial, the 4-year incidence of primary-outcome events was 6.0% (95% confidence interval [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 (P=0.02 for the absolute difference). In the endarterectomy trial, the 4-year incidence of primary-outcome events 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 (P=0.24 for the absolute difference). From day 0 to 44, in the stenting trial, no strokes or deaths occurred in the medical-therapy group and seven strokes and one death occurred in the stenting group; in the endarterectomy trial, three strokes occurred in the medical-therapy group and nine strokes occurred in the endarterectomy group.
Conclusions
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 four years than intensive medical management alone. Carotid endarterectomy did not lead to a significant benefit.
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