For release: Thursday, February 5, 1998
Investigators at more than 100 sites throughout the world have confirmed that surgery to remove fatty deposits from the arteries that carry blood to the brain can significantly cut the risk of stroke in patients with moderate as well as severe blockage.
The North American Symptomatic Carotid Endarterectomy Trial (NASCET), a 12-year study sponsored by the National Institute of Neurological Disorders and Stroke (NINDS), evaluated the effectiveness of carotid endarterectomy for patients with symptoms of stroke attributed to 30-99 percent narrowing (or stenosis) of the carotid artery. These results, announced today at the American Heart Association's 23rd International Joint Conference on Stroke and Cerebral Circulation in Orlando, Florida, show that patients clearly benefit from surgery if their carotid artery is more than 50 percent blocked.
"The results of this study were rather surprising to us," said H.J.M. Barnett, M.D., of The John P. Robarts Institute, London, Ontario, the lead investigator for the study. "We had not anticipated that surgery would be so beneficial for patients with severe stenosis, and are pleased that we were able to determine with some precision that surgery is also beneficial for those with a higher degree of moderate stenosis."
Previous reports from this group led to a radical change in the recommended treatment for severe (70-99 percent) carotid stenosis, or blockage. In 1991, a NINDS monitoring board reviewed the investigators' early data and determined that, together with appropriate medical care, surgery for patients with severe blockage prevented more strokes than medical treatment alone. Or in spite of the immediate risk associated with surgery, there was a 65 percent relative risk reduction (17 percent absolute risk reduction) of death or stroke over the next 2 years, which favored surgery (p< 0.001). The NINDS responded to this by halting the phase of the study involving patients with severe blockage, and issuing a nationwide alert to physicians asking them to consider the study results in making recommendations to their patients.
Since 1991, Dr. Barnett and colleagues have focused on determining the efficacy of carotid endarterectomy for symptomatic patients with moderate carotid stenosis (30-69 percent blockage). This part of the study required many more patients, each of whom had to be observed for at least 5 years. As reported today, for patients with the higher grades of moderate stenosis (50-69 percent), there was a statistically significant 29 percent relative risk reduction (6.5 percent absolute risk reduction) at 5 years (p=0.04). There was no significant benefit for patients with less than 50 percent stenosis.
The results of clinical trials are often expressed in terms of the "number needed to treat," that is, the number of patients who need to receive the treatment in order to prevent one event during a specific period of time. In this study, the investigators estimate that for patients with severe stenosis, only six patients need to undergo surgery to prevent one stroke in 2 years; eight patients need to undergo surgery to prevent one stroke in 5 years. For patients with moderate blockage (50-69 percent), 15 patients will undergo surgery to prevent one stroke in 5 years.
With the completion of the NASCET trial, patients with moderate stenosis will be better able to decide whether to risk surgery in order to prevent possible future strokes. According to the data, the point at which surgery begins to confer a significant benefit seems to be when the artery is 50 percent blocked.
The investigators at each of the sites used conventional carotid angiograms to determine the condition of the artery in all of the patients they studied. Dr. Barnett warns, "The results of NASCET must be interpreted only in light of the type of imaging we employed. Other forms of imaging may carry less risk but may lead to the wrong patients being submitted to surgery or, in some instances, denied it."
Further analysis of the patients with severe and moderate stenosis in the NASCET study indicates important risk factors in addition to the degree of stenosis. These include gender, diabetes, the type of stroke symptoms, blockage of the carotid artery on the opposite side, and the use of aspirin immediately prior to surgery. Without other complicating illnesses, age alone is not a worrisome risk factor. Risk factors affect patients in two ways. They can, particularly in combination, greatly increase a person's risk of having a stroke. In addition, these risk factors can increase the likelihood of surgical complications.
In fact, a low surgical complication rate was key to the successful achievement of the results of NASCET. During the clinical trial, 2 percent of patients had a disabling stroke or died around the time of surgery, while 6.7 percent had a stroke of any kind. Also, after 8 years of following patients who had surgery to alleviate severe stenosis, Dr. Barnett and his colleagues found that the benefit from endarterectomy was maintained.
"The decision to have surgery is a very individual one that depends on the health of the patient and the experience of the surgeon," said John R. Marler, M.D., NINDS senior medical officer. "Patients at high risk of stroke now have a much more realistic idea of the potential benefits from a surgery that is expensive and can have serious complications."
Another important preliminary finding first seen in the severe stenosis study, and now reinforced in the study of patients with moderate blockage, was the suggestion that patients taking large doses of aspirin had fewer surgical complications. This has led to the development of a new trial called Aspirin and Carotid Endarterectomy (ACE). This ongoing study is directly testing the efficacy of different doses of aspirin in reducing the risk of complications after carotid endarterectomy. The ACE Trial, which is also sponsored by the NINDS, and which uses many of the clinical centers participating in NASCET, is expected to enroll 2,800 patients, and should have preliminary results before the end of this year.
"This NASCET study represents 12 years of work by an extraordinarily effective team of more than 270 neurologists; 162 surgeons; 175 support personnel, including nurse practitioners who serve as clinical coordinators and statisticians; and 14,000 years of patient follow up," says Michael D. Walker, M.D., Director of the Division of Stroke, Trauma, and Neurodegenerative Disorders at NINDS. "We have now mapped the useful spectrum of stenosis, and patients and physicians can estimate the risks and benefits of surgery at each point."
A stroke occurs when brain cells are deprived of vital oxygen and nutrients because of decreased blood flow to portions of the brain. A blockage of cerebral blood vessels is the most frequent cause of stroke, and is responsible for at least 500,000 strokes each year. In the United States, stroke ranks as the third leading killer, after heart disease and cancer. On a world-wide basis, stroke kills more than 4 million people each year.
Carotid endarterectomy is the surgical procedure during which the carotid artery is opened, and the atherosclerotic plaque and fatty material deposited on the inside of the artery wall are removed. The two carotid arteries, one on each side of the neck, supply a major portion of blood to the brain. Stenosis of the carotid artery occurs when atherosclerotic plaques and fatty material build up on the inside of the artery wall and reduce blood flow to the brain. The degree of stenosis is often expressed as a percentage of the diameter of the normal artery. The greater the degree of stenosis, the greater the chance of a blood clot or floating piece of fatty material becoming lodged in the artery, cutting off blood flow to the brain, and causing a stroke.
The NINDS is the nation's principal supporter of research on the brain and nervous system and is part of the National Institutes of Health, located in Bethesda, Maryland.
Please visit the NINDS Stroke Information Page for more information on Stroke at http://www.ninds.nih.gov/health_and_medical/disorders/stroke.htm
Reporters: For more information, contact:
Margo Warren, NINDS, (301) 496-5751
Last Modified July 5, 2012