Results of NIH-Funded Clinical Trial Published in New England Journal of Medicine
Findings Have Immediate Implications for Clinical Practice
Sep 7, 2011
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 investigators published the results in today's online first edition of the New England Journal of Medicine. The National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health, funded the trial.
NewYork-Presbyterian Hospital and its two academic affiliates — Columbia University Medical Center and Weill Cornell Medical College — were part of the Stenting vs. Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial. In total, 50 medical centers participated, led by the Medical University of South Carolina in Charleston.
According to the study authors, the SAMMPRIS 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.
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 with the group who received the medical management alone.
Half the patients in the study received a medical regimen that included daily anti-thrombotic medications and aggressive control of blood pressure and cholesterol. The other 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 that 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.
The authors also emphasize that the study participants were in the highest risk category, with blockage or narrowing of arteries of 70 to 99 percent. Stroke patients with moderate cerebral arterial blockage (50 to 69 percent) were excluded because their risk of stroke is low with usual medical management, and researchers thought this group would be unlikely to benefit from stenting.
"This study provides an answer to a longstanding question by physicians — what to do to prevent a devastating second stroke in a high-risk population. Although technological advances have brought intracranial stenting into practice, we have now learned that, when tested in a large group, this particular device did not lead to a better health outcome," said Dr. Walter Koroshetz, deputy director of NINDS.
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 enrolled 451 patients at 50 sites across the United States. The investigators looked at whether patients had a second stroke or died within 30 days of enrollment, or had a stroke in the same area of the brain from 30 days to the end of follow-up. Researchers had hypothesized that compared with intensive medical therapy alone, the addition of an intracranial stenting system would decrease the risk of a stroke or death by 35 percent over two years.
Instead they found that 14.7 percent of patients (33) in the stenting group experienced a stroke or died within the first 30 days after enrollment, compared with 5.8 percent (13) of patients treated with medical therapy alone. There were five stroke-related deaths within 30 days, all in the stenting group, and one non-stroke-related death in the medical management group. During a follow-up period of just less than one year, 20.5 percent of patients in the stenting group and 11.5 percent of patients in the medical group had a stroke or death, or a stroke in the same area of the brain beyond 30 days, a highly significant difference in favor of the patients in the study's medical group. Based on these data, the Data and Safety Monitoring Board recommended that the NINDS stop new enrollment, and the NIH issued a clinical alert. All patients will continue to be followed for two years to determine the long-term effects of both interventions.
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.
In a previous NIH trial, stroke patients with criteria similar to those enrolled in SAMMPRIS were treated with less intensive medical management. Their comparable 30-day and one-year rates were 10.7 percent and 25 percent, respectively. The investigators note that comparisons with historical controls have limitations, but the much lower event rates in the medical group in SAMMPRIS suggest that the intensive medical management was effective in lowering the stroke risk.
Patients in the study were between 30 and 80 years old and had experienced a recent transient ischemic attack, 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.
Co-principal investigators at NewYork-Presbyterian Hospital/Columbia University Medical Center were Dr. Mitchell Elkind (associate professor of neurology and epidemiology at Columbia University College of Physicians and Surgeons and Mailman School of Public Health and a neurologist at NewYork-Presbyterian/Columbia) and Dr. Philip Meyers (associate professor of radiology and neurological surgery at Columbia University College of Physicians and Surgeons and co-director of neuro-endovascular services at NewYork-Presbyterian/Columbia). Co-principal investigators at NewYork-Presbyterian Hospital/Weill Cornell Medical Center were Dr. Y. Pierre Gobin (professor of radiology, professor of radiology in neurological surgery and professor of radiology in neurology at Weill Cornell Medical College, and director of interventional radiology at NewYork-Presbyterian/Weill Cornell) and Dr. Dana Leifer (associate professor of neurology at Weill Cornell Medical College and a neurologist at NewYork-Presbyterian/Weill Cornell). Drs. Gobin and Meyers were members of the SAMMPRIS credentialing committee.
NewYork-Presbyterian Hospital, based in New York City, is the nation's largest not-for-profit, non-sectarian hospital, with 2,353 beds. The Hospital has more than 2 million inpatient and outpatient visits in a year, including more than 220,000 visits to its emergency departments — more than any other area hospital. NewYork-Presbyterian provides state-of-the-art inpatient, ambulatory and preventive care in all areas of medicine at five major centers: NewYork-Presbyterian Hospital/Weill Cornell Medical Center, NewYork-Presbyterian Hospital/Columbia University Medical Center, NewYork-Presbyterian/Morgan Stanley Children's Hospital, NewYork-Presbyterian/The Allen Hospital and NewYork-Presbyterian Hospital/Westchester Division. One of the most comprehensive health care institutions in the world, the Hospital is committed to excellence in patient care, research, education and community service. NewYork-Presbyterian is the #1 hospital in the New York metropolitan area and is consistently ranked among the best academic medical institutions in the nation, according to U.S.News & World Report. The Hospital has academic affiliations with two of the nation's leading medical colleges: Weill Cornell Medical College and Columbia University College of Physicians and Surgeons.
Columbia University Medical Center
Columbia University Medical Center provides international leadership in basic, pre-clinical and clinical research, in medical and health sciences education, and in patient care. The Medical Center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians & Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Established in 1767, Columbia's College of Physicians and Surgeons was the first institution in the country to grant the M.D. degree and is now among the most selective medical schools in the country. Columbia University Medical Center is home to the largest medical research enterprise in New York City and state and one of the largest in the United States. For more information, please visit www.cumc.columbia.edu.
Weill Cornell Medical College
Weill Cornell Medical College, Cornell University's medical school located in New York City, is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research from bench to bedside, aimed at unlocking mysteries of the human body in health and sickness and toward developing new treatments and prevention strategies. In its commitment to global health and education, Weill Cornell has a strong presence in places such as Qatar, Tanzania, Haiti, Brazil, Austria and Turkey. Through the historic Weill Cornell Medical College in Qatar, the Medical College is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances — including the development of the Pap test for cervical cancer, the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial of gene therapy for Parkinson's disease, and most recently, the world's first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient. Weill Cornell Medical College is affiliated with NewYork-Presbyterian Hospital, where its faculty provides comprehensive patient care at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. The Medical College is also affiliated with the Methodist Hospital in Houston. For more information, visit Weill Cornell Medical College.