Stroke-a sudden loss of blood to the brain caused by a blocked blood vessel-is one of the most common causes of death in America, and stroke survivors often experience serious long-term symptoms.
Severe narrowing of the carotid arteries, which supply blood to the brain, is a major risk factor for stroke. While multiple treatment options can reduce that risk for patients with narrow carotids, until now, it was unclear which options helped the most.
As part of a multinational clinical trial, researchers and clinicians at University of Utah Health brought gold-standard, high-intensity medical care to prevent stroke to patients, while showing that adding another treatment option called stenting to intensive management can lower the risk even more. The results are already being put into practice at University of Utah Health to ensure patients receive the best care possible.
"The trial was truly instrumental in paving the way for evidence-based guidance. This basically changes history and changes what's considered standard of care."
Stopping Strokes Before They Start
For patients with severe narrowing of the carotid arteries who haven't had a stroke, the current first-line strategy to prevent strokes is non-surgical medical management. Medical management for stroke prevention has advanced immensely over the past few decades, combining lifestyle changes related to diet and exercise with powerful medications that lower cholesterol and reduce blood pressure.
Other important strategies to reduce stroke risk involve surgery: doctors can physically remove plaque from the arteries, or insert stents to keep the arteries wide open. These surgeries are effective in reducing a second stroke and have been established for decades. But the recent advances in non-surgical medical management left it unclear whether surgery could reduce the risk even more for patients who are already on top-of-the-line medication and haven't had an initial stroke.
"The big question is: can interventions, either an endovascular [through an artery] procedure or a surgical procedure, provide additional benefit to best medical management for stroke prevention in the 2020s?" explains Ramesh Grandhi, MD, a neurosurgeon at U of U Health and the clinical site co-investigator for the stenting trial.
To answer that question, clinicians, researchers, and over 2,400 patients at the U and around the world united in the CREST-2 clinical trial. The trial found that stenting is an effective addition for people undergoing the best possible medical management for severe narrowing of the carotid arteries-reducing the risk of stroke by half compared to medical management alone.
Beating the Gold Standard
The researchers in the trial were surprised by how much stenting helped because it was being compared to the best medical management possible.
All patients involved in the trial-whether they received an additional surgical intervention or not-were treated with gold-standard medications to reduce cholesterol and lower blood pressure, as well as having regular meetings with a lifestyle coach to support healthy behaviors and provide accountability.
"What is interesting to me is that for most patients-despite knowing they had carotid stenosis-when they joined the trial, their blood pressure and cholesterol were not well managed. It took being in CREST-2 and having regular appointments to ensure these critical risk factors were controlled."
The approach was effective. Across every group in the trial, patients experienced rapid and lasting reductions in cholesterol and blood pressure, which are major risk factors for stroke. "Everybody did really well," Aitken says. "Their risk factors were usually well-controlled soon after joining the trial, and those improvements were maintained."
For patients who were randomly assigned to receive stenting in addition to medical management, their risk of having a first-ever stroke within four years decreased even more, from 6% to slightly less than 3%.
"That stenting was found to be positive in diminishing the rate of stroke is a big deal. The highest tier of medical management, with lifestyle coaching, is really hard to beat. The medicines that we have at our disposal in 2026 are really quite remarkable, and these are some of the best-in-class methods of lowering cholesterol."
Majersik adds, "I think we were all really surprised with the results, as we've been practicing under the paradigm that the newest medical management was the best way to prevent stroke in patients with asymptomatic carotid stenosis. But now we have a new tool to prevent what is often a terrible disease."
How Clinical Trials Change Care
The results of the trial will meaningfully shape stroke prevention care at U of U Health and worldwide, the researchers say.
Based on the results, the researchers are already working to create and improve pathways for patients at the U so that people with severe narrowing of the carotids can be identified early and can more easily receive their best options for stroke prevention. This includes streamlining the process for patients who could benefit from a stent to receive one. "Our team is actively working on a pathway for how we're going to be treating and stenting patients," Majersik says.
Grandhi sees clinical trials as a key part of his work as a surgeon. "Working in medicine is most fundamentally about patient care, but it's also about how we can push health care forward for everyone," he says. "Participating in trials like this changes how we do health care-it informs us how we need to approach patients, it informs primary care doctors, and it really has such an influence on how we deliver health care. That's something that matters to me a lot, and I'm so proud of being at University of Utah Health because we participate in trials."
Grandhi adds that the willingness of U of U Health patients to be involved in clinical trials is a major strength of the institution.
"I think our patients are really excited to participate in trials, because they're really nice people who feel this connection of helping maybe you and me when we're 80 years old, and I think that's a profound thing that we have at U of U," Grandhi says. "Participating in this serves a higher purpose for me in terms of not only improving our patients' lives but improving the lives of countless patients for years to come."
