CLEVELAND -- Patients at a high risk for a second stroke who received intensive medical treatment had fewer strokes and deaths than patients who received a brain stent in addition to the medical treatment, a large nationwide clinical trial has shown. The results were published in the online first edition of the New England Journal of Medicine. University Hospitals (UH) Case Medical Center was one of the clinical research sites for the study.
The medical regimen included daily blood-thinning medications and aggressive control of blood pressure and cholesterol.
New enrollment in the study was stopped in April because early data showed significantly more strokes and deaths occurred among the stented patients at the 30-day mark compared to the group who received the medical management alone. The study had planned on recruiting 764 patients, but it stopped recruitment of patients after the Data Safety Monitoring Board (DSMB) determined there were significant findings with the first 451 patients.
Dr. Cathy Sila, Director of the Stroke and Cerebrovascular Center in the UH Neurological Institute and the principal investigator of the UH clinical research site, said, "Stroke specialists are all disappointed that stenting did not have the beneficial impact we thought it would have. We have always known that it is much more difficult to stent a blockage in the brain than in the heart but we cannot abandon this technology. We need to better understand the tolerances of the brain vasculature and continue to reengineer our tools.
"For now, we are thrilled that the effect of a very aggressive patient care plan to address all of their risk factors and make lifestyle changes to healthier living have demonstrated a significant impact in preventing stroke- and this impact is significant in as early as one month. I think this is a major achievement. The stroke or transient ischemic attack (TIA) is the 'warning shot across the bow' and we need to get into battle mode immediately," said Dr. Sila, who is also Professor of Neurology at Case Western Reserve University School of Medicine.
The study, named Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis (SAMMPRIS), was a trial of patients with a narrowing of the arteries in the brain due to atherosclerosis who had suffered a stroke and were at high risk for another stroke based on the location and the severity of the blockage and the instability of the plaque.
In addition to the intensive medical program, half of the patients in the study received an intervention of a self-expanding stent that widens a major artery in the brain and facilitates blood flow. One possible explanation for the higher stroke rate in the stented group is that patients who have had recent stroke symptoms sometimes have unstable plaque in their arteries which the stent could have dislodged, the study authors suggest. The study device, the Gateway-Wingspan intracranial angioplasty and stenting system, is the only system currently approved by the U.S. Food and Drug Administration (FDA) for certain high-risk stroke patients. The authors noted that although similar stenting systems that do not have FDA approval are being used in clinical practice, they did not evaluate those devices in this study
Dr. Sila said, "Based on prior studies, it was estimated that the rate of stroke and death at 30 days in this high risk group would be about 11 percent. The group that received aggressive medical therapy alone did far better than predicted with a 30 day stroke and death rate of only 5.8 percent. However, the group that received a stent as well as aggressive medical therapy did worse than predicted with a rate of 14.7 percent.
She said that stroke and death events continued to occur over a short follow-up period, less than one year, with the rate in medical therapy alone increasing to 12.2 percent and in the stenting group increasing to 20 percent. Patients in the trial are continuing their aggressive medical therapies and will be followed for up to 4.5 years to see if their long-term risk can be impacted.
Stroke is the fourth leading cause of death in the United States.
Stenosis, a blockage or narrowing of brain arteries caused by the build-up of plaque, accounts for more than 50,000 of the 795,000 strokes that occur annually nationwide. Stenosis is particularly common in African-Americans, Hispanics, Asian Americans and people with diabetes.
SAMMPRIS is the first stroke prevention trial to compare intracranial stenting with medical therapy and to incorporate intensive medical management into the study design. This includes a daily dosage of 325 milligrams of aspirin; 75 milligrams a day of clopidogrel, a medication used to prevent blood clots, for 90 days after enrollment; and aggressive management of key stroke risk factors – high blood pressure and high levels of low density lipoprotein (LDL), the unhealthy form of cholesterol. All patients also participated in a lifestyle modification program which focused on quitting smoking, increasing exercise, and controlling diabetes and cholesterol.
"The SAMMPRIS study results have immediate implications for clinical practice. Stroke patients with recent symptoms and intracranial arterial blockage of 70 percent or greater should be treated with aggressive medical therapy alone that follows the regimen used in this trial as closely as possible," said Marc Chimowitz, M.B.Ch.B., of the department of neurosciences at the Medical University of South Carolina in Charleston, and first author of the NEJM article.
Patients in the study were between 30 and 80 years old and had experienced a recent TIA, a type of stroke that resolves within 24 hours, or another type of non-disabling stroke, which was caused by a large degree of stenosis in a cerebral artery.
The National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health, funded the trial.
About University Hospitals
University Hospitals serves the needs of patients through an integrated network of hospitals, outpatient centers and primary care physicians. At the core of our health system is University Hospitals Case Medical Center. The primary affiliate of Case Western Reserve University School of Medicine, University Hospitals Case Medical Center is home to some of the most prestigious clinical and research centers of excellence in the nation and the world, including cancer, pediatrics, women's health, orthopedics and spine, radiology and radiation oncology, neurosurgery and neuroscience, cardiology and cardiovascular surgery, organ transplantation and human genetics. Its main campus includes the internationally celebrated UH Rainbow Babies & Children's Hospital, ranked among the top children's hospitals in the nation; UH MacDonald Women's Hospital, Ohio's only hospital for women; and UH Seidman Cancer Center, part of the NCI-designated Case Comprehensive Cancer Center. For more information, go to www.uhhospitals.org
New England Journal of Medicine