CINCINNATI—A major study of people at risk for stroke, conducted in part at the University of Cincinnati (UC) Neuroscience Institute at University Hospital, shows that two medical procedures designed to prevent future strokes are safe and effective overall.
Physicians will now have more options in tailoring treatments for their patients at risk for stroke. In the trial of 2,502 participants, carotid endarterectomy (CEA), a surgical procedure to clear blocked blood flow and considered the gold standard in preventive treatment, was compared to carotid artery stenting (CAS), a newer and less invasive procedure that involves threading a stent and expanding a small protective device in the artery to widen the blocked area and capture any dislodged plaque. The study appears May 26, 2010, in the online first edition of the New England Journal of Medicine.
One of the largest randomized stroke prevention trials ever, the Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST) took place at UC Health University Hospital and 116 other centers in the United States and Canada over a nine-year period. CREST compared the safety and effectiveness of CEA and CAS in patients with or without a history of stroke. The trial was funded by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health, and led by investigators at the Mayo Clinic, Jacksonville, Fla., and the University of Medicine and Dentistry of New Jersey in Newark.
Cincinnati’s portion of the trial was led by Mario Zuccarello, MD, professor and chairman of the department of neurosurgery at UC and director of cerebrovascular surgery, and Andrew Ringer, MD, associate professor and director of endovascular neurosurgery at UC. Zuccarello and Ringer are members of the UC Neuroscience Institute and the Mayfield Clinic neurosurgical practice.
The overall safety and efficacy of the two procedures was largely the same, with equal benefits for men and for women and for patients who had previously had a stroke and for those who had not. However, when the investigators looked at complications—the number of heart attacks and strokes—they found differences. In the weeks following the procedure, there were more heart attacks in the surgical group, 2.3 percent compared to 1.1 percent in the stenting group; and more strokes in the stenting group, 4.1 percent versus 2.3 percent for the surgical group.
The study also found that the age of the patient made a difference. At approximately age 69 and younger, stenting results were slightly better, with a larger benefit for stenting the younger the age of the patient. Conversely, for patients older than 70, surgical results were slightly superior to stenting, with larger benefits for surgery the older the age of the patient.
"Older patients who were not at risk for surgery did not do as well with stents,” Ringer explains, "because arteries tend to become twisty and bent with age. It is harder to place a stent in these arteries that have become more curved. It’s harder to navigate those bends and curves. But it’s not harder to make an incision in the neck and reach the artery for surgery. In younger patients whose arteries are straighter, by contrast, it’s easier to place the stent.”
Among patients for whom surgery was a risk, the outcomes were different.
"Patients who are considered at high risk for surgery—who have unstable heart disease or chest pain at rest, who have poor cardiac pump function, who have had prior surgery or radiation to the neck, or whose stenosis is so high that it’s difficult to reach surgically—do better with stents than surgery,” Ringer says.
Stroke, the third leading cause of death in the United States, is caused by an interruption in blood flow to the brain by a clot or bleeding. The carotid arteries on each side of the neck are the major source of blood flow to the brain. The buildup of cholesterol in the wall of the carotid artery, called atherosclerotic plaque, is one cause of stroke. Because people with carotid atherosclerosis also usually have atherosclerosis in the coronary arteries that supply the heart, the CREST trial tracked the rate of heart attacks in addition to stroke and death.
In CREST, approximately half the patients had recent, carotid-disease symptoms, such as a minor stroke, or a transient ischemic attack (TIA), indicating a high risk for future stroke. The other half had no symptoms but were found to have narrowing of the carotid artery on one of a variety of tests assessing carotid narrowing and plaque. Such patients, termed asymptomatic, are at much lower risk of stroke than those with symptoms.
One of the strengths of the study, according to investigators, is that CREST was conducted in a variety of real-world settings, including large and small public and private hospitals. Physicians had to demonstrate a high degree of proficiency and safety in order to participate in the trial. The study found no significant differences in the outcomes, no matter what type of medical specialist performed the stenting procedure, including cardiologists, neuroradiologists, interventional radiologists, vascular surgeons and neurosurgeons.
The researchers point out that the rate of stroke and death in the surgical group was the lowest ever reported in a large stroke prevention trial. The rate for stroke and death in carotid stenting was also the lowest yet reported in any randomized trial.
As a result, the pivotal differences were the lower rate of stroke following surgery and the lower rate of heart attack following stenting, according to the investigators. A year after the procedure, the patients who had suffered a stroke reported that the effects of the stroke had a greater impact on their quality of life than was reported by those patients who had suffered a heart attack.
The CREST investigators concluded that while CEA has a proven record and long-term durability, both CAS and CEA are safe and useful tools in the right setting for stroke prevention, and technology continues to improve each procedure.
Partial funding for the study was supplied by Abbott, of Abbott Park, Ill., the maker of the stents. Zuccarello and Ringer report no financial ties to Abbott.