George Howard, Ph.D., and Mark Harrigan, M.D.According to a 2025 American Heart Association report, 87 percent of nearly 800,000 annual stroke events in the United States are ischemic, in which blood flow to the brain is blocked. A new study, published in The New England Journal of Medicine, has found that adding a stent procedure to intensive medical therapy significantly lowers the risk of stroke in asymptomatic patients with carotid stenosis, a severe narrowing of the carotid artery that carries blood to the brain.
George Howard, DrPH, and Lloyd Edwards, Ph.D., both professors in the Department of Biostatistics at the University of Alabama at Birmingham School of Public Health, are at the forefront of this cutting-edge research, working closely with the Clinical Coordinating Center at Mayo Clinic Jacksonville. Howard and Edwards led the Statistical and Data Coordinating Center at UAB in the Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST-2), the largest study to date comparing current treatment approaches for carotid artery narrowing. This is a condition where plaque buildup in arteries prevents blood supply to the brain and head, eventually causing a stroke.
The CREST-2 trial consisted of two parallel, randomized clinical trials conducted at 155 medical facilities in five countries, including Australia, Canada, Israel, Spain and the U.S. Each trial enrolled more than 1,200 adults with severe carotid artery narrowing of 70 percent or greater who had not had a stroke or transient ischemic attack or mini stroke in the past six months. The CREST-2 team analyzed the occurrence of stroke and death within 44 days of stenting or surgery, and the occurrence of stroke over four years on the same side of the body as the narrowed artery.
In one trial, participants received stenting plus intensive medical therapy or medical therapy alone. In the other, participants received endarterectomy plus medical treatment or medical therapy alone. All participants received comprehensive medical care, including lifestyle coaching and medication as needed, to manage their blood pressure, low-density lipoprotein cholesterol and diabetes, and to help them stop smoking.
Supplementing a stent to medical management significantly reduced the 4-year risk of stroke by about one-half, from 6 percent for medical management alone to 2.8 percent. The addition of endarterectomy reduced the 4-year stroke risk from 5.3 percent for medical management alone to 3.7 percent, but this reduction was not significant.
“Findings from this clinical trial will help prevent strokes in high-risk patients, help clinicians make informed decisions and could reshape treatment guidelines for asymptomatic carotid stenosis,” Howard said.
Although surgery and stenting have long been used to open carotid arteries, newer medications and better risk factor control have raised questions about whether these procedures are needed for people who do not have symptoms.
“The results of this important trial will allow us to provide state-of-the-art management to prevent strokes in patients with asymptomatic carotid stenosis,” said Mark Harrigan, M.D., professor of neurosurgery and principal investigator for the trial at the UAB site.
Virginia Howard, Ph.D.To ensure a seamless workflow and achieve these landmark results, the UAB School of Public Health served as the Statistical and Data Coordinating Center. The school’s Survey Research Unit and the DATA Coordinating and Collaborative Research Unit, which include researchers from departments of Epidemiology, Biostatistics, Health Care Organization and Policy and Health Behavior, worked collaboratively.
“We have a tremendous team who worked extremely well together with all the components,” said Virginia Howard, Ph.D., distinguished professor of epidemiology and a co-investigator. “These components included programming, data management, complex statistical analyses, telephone interviews with patients, training study coordinators and managing international sites to produce high-quality data.”
Additional collaborators from the UAB Marnix E. Heersink School of Medicine included Ronald Lazar, Ph.D., endowed chair and director of the Evelyn F. McKnight Brain Institute and Virginia Wadley, Ph.D., associate professor in the Division of Gerontology, Geriatrics and Palliative Care, and Stroke Neurologist Angela Shapshak, M.D., professor in the Department of Neurology.
This study was funded by the National Institute of Neurological Disorders and Stroke, within the National Institutes of Health.