Carotid artery disease remains a major contributor to ischemic stroke, one of the leading causes of death and long-term disability in the United States. While symptomatic carotid stenosis has well-established treatment pathways, the management of asymptomatic carotid artery disease remains an area of ongoing debate. Traditional treatment methods such as intensive medical management have largely functioned as the standard of care for asymptomatic carotid artery disease, with revascularization (carotid endarterectomy or carotid artery stenting) a consideration for patients with asymptomatic stenosis greater than 70 percent.
With the improvements in intensive medical therapy over the past three decades, I have grappled with decisions about when to offer an asymptomatic patient carotid artery intervention. However, recent data from the large, NIH-funded, randomized clinical trial, CREST-2, show that pairing minimally invasive transfemoral carotid artery stenting with intensive medical therapy and risk factor modification measures actually enhances stroke prevention outcomes, a real turning point for the vascular care field, in my view, and a strong affirmation of the value of implementing both approaches for patient care.
Carotid artery disease is the narrowing of the arteries in the neck by 50 percent or more due to a buildup of atherosclerotic plaque, and accounts for roughly 20 percent of ischemic strokes. Stroke remains a leading cause of death and disability globally, with 60 percent of stroke patients living with some form of permanent damage. Most patients with carotid artery stenosis are asymptomatic until it becomes severe. The challenge with this condition as a physician is that for many patients with asymptomatic carotid artery stenosis, the first symptom they will experience is stroke. While some patients will have warning symptoms such as a transient ischemic attack (TIA) or temporary vision loss (amaurosis fugax), many patients will have no warning before experiencing an ischemic stroke.
When I work with patients, how we integrate intensive medical management can look different depending on the individual. Treatment typically involves a combination of cholesterol-lowering medications, antiplatelet therapy, blood pressure control, diabetes/hemoglobin A1C control measures, and lifestyle factors to control blood pressure. Newer medical therapies such as sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) agonists are also increasingly being recognized for their benefit in treating atherosclerotic diseases and may play an emerging role in the management of patients with asymptomatic carotid artery stenosis. While these treatments are noninvasive, achieving optimal stroke prevention goals can be very difficult due to a variety of factors, including patient adherence, variability in individual responses to treatments, and balancing pre-existing conditions. Outside barriers such as access to care, social determinants of health, and patient health literacy must also be acknowledged.
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Understanding this complex web of factors influencing care, the CREST-2 (Carotid Revascularization Endarterectomy vs. Stenting Trial) clinical trial sought to identify the best treatment strategy for patients with severe (>70 percent narrowing in the carotid artery) asymptomatic carotid artery stenosis. The 2,485 patients enrolled in the trial were divided into 2 groups to examine the impact of intensive medical management when paired with either carotid endarterectomy (CEA) or transfemoral/transradial carotid artery stenting (CAS). What researchers found was a significant reduction in total stroke or death outcomes in the first 44 days and ipsilateral ischemic stroke in the follow-up period from 45 days to 4 years when patients were treated with medical management and CAS intervention.
While it’s clear that stenting the carotid artery in symptomatic patients is beneficial, there has always been ongoing discussion in our community about the benefits of stenting for asymptomatic patients, and persistent questions remain about whether stenting is as effective as carotid endarterectomy. This large, randomized trial clearly and robustly demonstrated stenting reduced the risk of stroke in asymptomatic patients, even when patients were already receiving high-quality medical therapy. These results provide strong scientific support for this combined approach and further reinforce the role of carotid revascularization, particularly carotid stenting, in patients with suitable anatomy.
Prior to results of CREST-2, physicians were working within a narrow set of clinically validated options. Since enrollment was completed for the CREST-2 trial in August 2024, new carotid stent platforms have been introduced into the market, showing better results than traditional carotid stenting systems. CREST-2 and the outstanding results we are seeing with new carotid platforms give us a stronger footing for recommending carotid revascularization for asymptomatic patients. With these robust results, physicians should feel encouraged to make evidence-backed recommendations implementing minimally invasive procedures. I am far more inclined to refer high-grade asymptomatic carotid artery stenosis patients for carotid stent revascularization procedures, given this data-driven understanding of the best treatments for this population.
CREST-2 marks an important shift in how we care for patients with asymptomatic carotid artery disease. It’s clear from the CREST-2 trial that transfemoral/transradial carotid artery stenting and intensive medical management, together, are significantly impactful. We have the clinical data, we have new tools, and we have a population whose long-term outcomes can be greatly improved by the intersection of the two. I am excited to learn how this space evolves and how other thought leaders in this space react to CREST-2 and incorporate the study findings into their clinical practice.
John R. Laird, Jr. is an interventional cardiologist.
