Carotid stenosis occurs when plaque builds up in the carotid artery, narrowing the vessel and restricting blood flow to the brain and can lead to stroke. However, asymptomatic high-grade carotid stenosis (ACS) occurs when the artery is narrowed by at least 70-80% without a recent stroke, significantly increasing the risk of future stroke, cardiovascular events, and cognitive decline. For decades, clinicians and researchers debated the management of ACS, balancing clinical and procedural risk against constantly evolving medical therapies.
In November 2025, the New England Journal of Medicine published data from the Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Study (CREST-2), focused on revascularization practices to manage stroke risk in ACS patients. The reaction from the clinical community has been polarizing, but why and what should clinicians take from this research?
While CREST-2 can stand as a guideline for understanding ACS therapies in case-by-case scenarios, it’s critical that trial conclusions do not replace clinical judgment and years of previous research.
CREST-2 findings should not be interpreted as a verdict against surgical expertise
CREST-2 outcomes should not diminish the value of ACS intervention when performed by experienced vascular surgeons — the only medical specialty trained solely to treat, prevent, and manage vascular conditions.
Real-world registry data from the Vascular Quality Initiative (VQI) reinforce this conclusion. In everyday clinical settings, CEA continues to meet or exceed standard stroke and death rate limits both before and after surgery. Analyses using VQI data also consistently find higher stroke rates with transfemoral carotid artery stent (TFCAS) than with carotid endarterectomy (CEA), findings that reflect decades of randomized trial data.
Over the last 15 years, eight randomized controlled trials directly compared TFCAS and CEA — seven of which demonstrated a persistently increased risk of stroke after 30 days with TFCAS. Since CREST-2 did not directly compare TFCAS and CEA, its findings do not cancel established evidence supporting CEA in select patients and the consistent outcomes that vascular surgeons have demonstrated.
Trial design & outcomes: What two parallel trials show us and what they do not
CREST-2 consists of two separate, observer-blinded randomized controlled trials focused on uncovering how revascularization can work alongside medical therapies in ACS patients at risk of stroke. The first trial compared intensive medical management (IMM) alone to IMM and TFCAS, while the second trial compared IMM alone to IMM and CEA.
The first trial found the four-year stroke risk at 6.0% (IMM) vs 2.8% (TFCAS + IMM). The second trial had a four-year stroke risk of 5.3% (IMM) vs 3.7% (CEA + IMM). Although both TFCAS and CEA reduced long-term stroke risk compared with IMM alone, neither found superiority of TFCAS over CEA.
Yet, CREST-2 data present these trials in a way that influences readers to view them as direct comparisons, which may lead to the mistaken conclusion that TFCAS outperformed CEA in reducing stroke risk. However, both trials used strict enrollment criteria (specifically TFCAS for select carotid lesions done by select high-performance providers), resulting in distinct patient populations and unique outcomes. It is not possible to draw parallels between TFCAS and CEA study findings without risking inaccurate conclusions that can affect real-world applications.
CREST-2 reflects idealized medical therapy, not routine clinical practice
Due to the study’s highly controlled enrollment criteria, conclusions do not represent real-world treatment scenarios. Instead, they demonstrate what is possible under trial-level medical management.
IMM often requires strict “bad” cholesterol (or LDL) and blood pressure goals, lifestyle changes, medications, and close monitoring, which does not correlate to real-life for ACS patients. The study also began before contemporary practice patterns gained widespread adoption. For example, the trial did not include transcarotid artery revascularization (TCAR), which now plays a central role in ACS treatment across the United States. Essentially, the study’s conclusions do not reflect current treatment approaches. Revascularization decisions in clinical practice must account for realistic upkeep, not theoretical best-case scenarios.
CREST-2 Is a milestone, not the final word
While the CREST-2 study findings are important in the broader landscape of ACS research, they do not fully capture today’s treatment ecosystem. The landscape continues to evolve, with ongoing improvements to revascularization techniques, patient selection, and the growing role of registry data — developments that postdate the initiation of CREST-2.
CREST-2 should inform, not replace, decades of compiled evidence seeking to manage stroke risk in patients with carotid disease. Future care decisions should continue to integrate randomized trial data, document real-world evidence (including VQI outcomes), and emphasize insight from trained and experienced vascular surgeons.
Authors:
Keith D. Calligaro, MD, is a nationally recognized vascular surgeon and leader in advanced vascular and endovascular care at Penn Medicine in Philadelphia, Pennsylvania. He serves as Chief of Vascular Surgery and Endovascular Therapy at Pennsylvania Hospital and is Program Director of the Vascular Surgery Fellowship. He is also the current President of the Society for Vascular Surgery. With decades of experience, Dr. Calligaro specializes in the diagnosis and treatment of complex diseases affecting the arteries and veins, including aortic aneurysms, carotid artery disease, and peripheral vascular conditions. Additionally, Dr. Calligaro is a Professor of Clinical Surgery and an active educator and researcher, contributing to advancements in vascular surgery and training the next generation of specialists.
Ali F. AbuRahma, MD, is an internationally recognized vascular surgeon and leader in vascular and endovascular care at Charleston Area Medical Center (CAMC) in Charleston, West Virginia. He serves as Tenure Professor/Chief Emeritus of Vascular and Endovascular Surgery at West Virginia University Charleston, Medical Director of the Vascular Laboratory, and Co-Director of the Vascular Center of Excellence. Dr. AbuRahma has decades of experience treating complex arterial diseases and aortic aneurysms, including carotid artery disease, cerebrovascular conditions, and peripheral vascular disease. A prolific researcher and educator, Dr. AbuRahma has authored hundreds of peer-reviewed publications (major emphasis is cerebrovascular disease), book chapters, and textbooks in vascular surgery and has held leadership roles in major professional societies, including serving as President of the Society for Vascular Surgery.
Marc L. Schermerhorn, MD, is a nationally recognized vascular surgeon at Beth Israel Deaconess Medical Center and Chief of the Division of Vascular and Endovascular Surgery in Boston, Massachusetts. He specializes in the treatment of complex vascular disease, with expertise in abdominal and thoracic aortic aneurysm repair, aortic dissection, carotid artery interventions, and lower extremity angioplasty and surgery. Dr. Schermerhorn is an active leader in the vascular surgery community, with involvement in major professional societies and contributions to clinical research.
Photo: nevarpp, Getty Images
