Caitlin Hicks (Baltimore, USA) reflects on CREST-2 following publication of the trial late last year.
After nearly a decade of enrolment and follow-up, CREST-2 provides the most contemporary randomised evidence comparing carotid revascularisation with intensive medical therapy for asymptomatic disease. The investigators deserve considerable credit. Randomised trials in asymptomatic carotid disease have become increasingly difficult as medical therapy improves and clinical practice evolves. CREST-2 required sustained collaboration across hundreds of sites, rigorous credentialing of operators, and a highly structured protocol for risk-factor management.
The most important lesson from CREST-2 is not about which procedure performs best. Instead, the trial highlights just how dramatically the natural history of asymptomatic carotid disease has changed. Put simply: modern medical therapy works.
The most striking observation in CREST-2 is the low stroke rate observed among patients treated with intensive medical therapy. The annual stroke risk in the medically managed cohorts was approximately 1.5% per year.1 That number matters because it fundamentally reshapes the risk–benefit equation that has historically driven decisions about intervention.
Earlier trials that established the benefit of carotid revascularisation were conducted in an era when medical therapy was far less effective. Statins were not widely used, blood pressure control was less aggressive, and preventive cardiovascular care was inconsistent. CREST-2 reflects a very different treatment landscape. With contemporary medical therapy, including aggressive lipid control, antiplatelet therapy, and structured follow-up, many patients with asymptomatic carotid stenosis now face a relatively low short-term risk of stroke. For some patients, particularly older individuals with competing comorbidities, this means the immediate procedural risk of intervention may outweigh potential longterm benefits.
That does not mean carotid revascularisation for patients with asymptomatic disease is obsolete. But it does mean the threshold for intervention deserves careful reconsideration.
It is important to recognise that the results of CREST-2 were achieved under highly controlled conditions.2 Patients enrolled in the trial received structured follow-up and intensive risk-factor management that may be difficult to reproduce in routine clinical practice. Medication adherence was closely monitored, and risk factors were aggressively addressed.
Operator credentialling was also rigorous. Interventionists performing transfemoral carotid artery stenting were required to demonstrate extensive experience before being allowed to participate in the trial, and a significant proportion of applicants were not approved.3
In addition, patients with unfavourable anatomy, including complex arch anatomy or calcified lesions, were excluded from stenting randomisation. In contrast, anatomic limitations for carotid endarterectomy were minimal.
These safeguards undoubtedly contributed to the excellent outcomes reported in CREST-2. The question now facing clinicians is not whether these outcomes are achievable, but whether they are reproducible in everyday practice.
One of the most notable aspects of CREST-2 is what the trial did not include. Transcarotid artery revascularisation (TCAR) has become a major component of carotid intervention in the USA. However, TCAR was not incorporated into the CREST-2 trial design because the study began before the technology achieved widespread adoption. As a result, CREST-2 compares intensive medical therapy with carotid endarterectomy and transfemoral carotid stenting, but does not address the approach that many vascular surgeons use with increasing frequency in contemporary practice.
Registry data suggest favourable outcomes with TCAR, particularly when compared with transfemoral stenting.4 Whether TCAR would have influenced the conclusions of CREST-2 remains unknown, but its absence is an important consideration when applying the trial’s findings to contemporary practice.
So, what should clinicians take away from CREST-2?
First, the trial reinforces the importance of aggressive medical therapy for all patients with carotid disease. Risk-factor control is no longer simply an adjunct to intervention; it is a central component of stroke prevention.
Second, the CREST-2 results highlight the importance of patient selection. Not every patient with asymptomatic carotid stenosis requires intervention. For some individuals, such as older patients with well-controlled risk factors, medical therapy alone may be a reasonable strategy. Other patients, such as those with long life expectancy and favourable anatomy, may still derive meaningful benefit from revascularisation. Even modest annual stroke risk can accumulate over time, making long-term risk reduction relevant for carefully selected individuals.
Finally, shared decision-making will become increasingly important. Patients should understand both the relatively low stroke risk associated with modern medical therapy and the potential long-term benefits—balanced against the short-term risks—of intervention.
CREST-2 does not end the debate over asymptomatic carotid stenosis, but it reframes it. The future of carotid disease management will depend on better tools to identify which plaques are truly high risk and which patients stand to benefit most from intervention. Advances in imaging, plaque characterisation, and risk stratification may ultimately help guide these decisions.
In the meantime, the central message of CREST-2 is clear: optimise medical therapy, intervene selectively, and individualise treatment decisions.
Carotid revascularisation remains an important tool for preventing stroke. But CREST-2 reminds us that the goal is not simply to perform procedures—it is to ensure that the right patients receive the right treatment at the right time. This shift from routine intervention toward precision patient selection may ultimately be CREST-2’s most lasting contribution.
References:
- Brott T G, Howard G, Lal B K et al; CREST-2 investigators. Medical management and revascularization for asymptomatic carotid stenosis. N Engl J Med. 2026; 394(3): 219–31.
- Turan T N, Voeks J H, Chimowitz M I et al. Rationale, design, and implementation of intensive risk factor treatment in the CREST-2 trial. Stroke. 2020; 51(10): 2960–71.
- Lal B K, Meschia J F, Roubin G S et al; CREST-2 investigators. Factors influencing credentialing of interventionists in the CREST-2 trial. J Vasc Surg. 2020; 71(3): 854–61.
- Columbo J A, Martinez-Camblor P, Stone D H et al. Effectiveness of transcarotid vs transfemoral carotid stenting for stroke prevention. JAMA Netw Open. 2025; 8(4): e259143.
Caitlin Hicks is vice chair of research in the Department of Surgery and associate professor of surgery at The Johns Hopkins University School of Medicine in Baltimore, USA.
DISCLOSURES: The author declared no relevant disclosures.
