Is medicine as safe and effective as surgery or stenting in preventing a stroke caused by the buildup of plaque in the carotid artery? Thomas G. Brott, M.D., a neurologist at Mayo Clinic in Florida, aims to find out.
"It's a critical question. The quality medicines we have today may mean that it is not necessary to perform invasive procedures on patients who do not have warning signs of stroke," Dr. Brott says. "More than 100,000 carotid surgeries and carotid artery stentings are performed each year in the United States on such patients at risk - and that may not be necessary."
To find the answer, the National Institute of Neurological Disorders and Stroke (NINDS) has awarded Dr. Brott and his colleague, James Meschia, M.D., $39.5 million - one of the largest grants ever awarded to Mayo Clinic in Florida investigators. The grant funds a seven-year clinical trial that will enroll 2,480 patients in 120 centers in the United States, Canada, Europe and Australia. The study, known as CREST-2, is expected to begin enrolling patients this summer. Management of the patient data and the statistical analysis will be carried out at the University of Alabama at Birmingham under the direction of George Howard, Dr.PH.
Dr. Brott says it's time for medical management of carotid artery stroke risk to be re-examined. The last studies of the effectiveness of medicine in reducing carotid stroke risk were initiated in the 1990s, when researchers looked at medicine versus surgery, also known as carotid endarterectomy (CEA). At that time, carotid artery stenting (CAS) hadn't been developed, and drugs such as statins to lower cholesterol had just reached the market.
"We really think we need an answer as to the best management of stroke risk for our patients," Dr. Brott says. "The data we have on medical management is decades old, but the drugs we are using today are much more sophisticated."
CREST-2 is building upon the infrastructure developed in the CREST (Carotid Revascularization Endarterectomy versus Stenting) clinical trial, which Dr. Brott also led. The findings, announced in May 2010, found that CEA and CAS provided similar results in overall safety and effectiveness, whether or not patients had symptoms of carotid disease. There were differences, however, in the weeks following the procedures in patients - those who received a stent had more strokes, and patients treated surgically had more heart attacks. Age also made a difference - people younger than 70 did better with stents while those over 70 had better results with surgery.
CREST-2 will consist of two parallel but separate studies, conducted in patients with asymptomatic carotid disease who have at least 70 percent or higher blockage in one of their carotid arteries but who have not suffered a stroke and have not had warning signs.
One part of CREST-2 will compare a combination of CEA and medical management to medical management alone, and the other part will study CAS combined with medical management compared to medical management alone. Therefore, all enrolled patients will be treated with medical management, which can include antiplatelet drugs to prevent clotting - statins, among other agents - and when appropriate, drugs to manage hypertension and diabetes.
"We will ensure, at all of the 120 centers in CREST-2, that patients receive the highest-quality medical management possible, along with best practices in surgery and stenting," Dr. Brott says. "CREST-2 should offer us the definitive answer to what works best in which patients to treat carotid disease."
The study is funded by NINDS grant 1U01NS080168-01A1.