ARTICLE IN BRIEF
A new analysis of the SAMMPRIS trial outcomes confirmed and extended the superiority of aggressive medical therapy over stenting for intracranial stenosis at a follow-up of 32 months.
The benefits of aggressive medical therapy alone compared with medical therapy and stenting for intracranial stenosis appear to persist over time.
A long-term follow-up of patients in the Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis (SAMMPRIS) trial showed that the early comparative benefit of aggressive medical therapy alone that was found in an initial trial begun in 2008 persists at 32 months follow-up. The follow-up study, which was published in the online Oct. 26 issue of The Lancet, confirms and extends the superiority of aggressive medical therapy over stenting that the earlier trial, published in the New England Journal of Medicine in 2011, found at 30 days.
“The benefits of aggressive medical therapy persist over the long term and should be our preferred treatment, not only for intracranial stenosis, but for all patients with stroke or transient ischemic attacks who have large vessel atherosclerosis,” said Seemant Chaturvedi, MD, professor of neurology at Wayne State University School of Medicine, who was a member of the study team, in an interview with Neurology Today.
In the study, which was funded by the National Institute of Neurological Disorders and Stroke, researchers randomly assigned 451 patients with recent transient ischemic attack or stroke related to 70–99 percent stenosis of a major intracranial artery to aggressive medical management or aggressive medical management plus percutaneous transluminal angioplasty and stenting with the Wingspan stent. The primary endpoint was any one of the following: stroke or death within 30 days after enrollment, ischemic stroke in the territory of the qualifying artery beyond 30 days of enrollment, or stroke or death within 30 days after a revascularization procedure of the qualifying lesion during follow-up.
Enrollment in SAMMPRIS began on Nov. 25, 2008, but was stopped on April 5, 2011, because the 30-day rate of stroke and death was higher in the group receiving stenting. When enrollment was stopped, fewer than half the 451 patients in the trial had been followed up for longer than one year. Since then, patients in both treatment groups have been followed up for two more years to establish whether the early benefit in the medical group would persist over longer follow-up, or whether the medical group would have a high incidence of late strokes that would eliminate the early efficacy gap between the two groups.
During a median follow-up of 32.4 months, 34 of 227 patients in the medical group and 52 of 224 patients in the stenting group had a primary endpoint event. The cumulative probability of the primary endpoints was smaller in the medical group versus the percutaneous transluminal angioplasty and stenting (PTAS) group.
Primary endpoint rates were higher in the stenting group at one year, two years, and three years, increasing to a 9 percent difference by year three. These adverse events occurred more in the stenting group than in the medical group: any stroke (59 of 224 patients versus 42 of 227 patients) and major hemorrhage (29 of 224 patients versus 10 of 227 patients).
Dr. Chaturvedi told Neurology Today that the hypothesis when SAMMPRIS was undertaken was that the group receiving both medical therapy and stenting would benefit more. “That hypothesis was turned on its head when we saw that 14 percent of the patients in the stenting group died or had a stroke within 30 days,” he said. “The pleasant surprise was how well aggressive medical therapy worked. Now we know that the benefits of aggressive medical therapy persist over time, and it should be our first line treatment.”
Dr. Chaturvedi explained that the medical therapy consisted of blood thinners — aspirin for the duration of the follow-up and clopidogrel for 90 days after enrollment — and blood pressure (BP) monitoring. “BP monitoring was targeted to national guidelines, which meant for diabetic patients a BP of less than 140 and for diabetic patients, less than 130,” he said.
A third component was aggressive treatment of cholesterol with rosuvastatin. Finally, the patients participated in a lifestyle modification program, in which a coach contacted the patients by telephone every two weeks for the first three months after enrollment, and then monthly after that. The program included baseline assessment of risk factors, formulating an action plan — with a focus on exercise, correct nutrition, weight management, and tobacco smoking cessation — and follow-up counseling sessions to help patients acquire the skills, motivation, and support needed to implement and adhere to their individualized action plan.
James C. Grotta, MD, professor of neurology and chair of the department of neurology at the University of Texas Medical School at Houston, said it had been anticipated that the stenting group might “catch up” over time in terms of benefit. “The theory was that when you stent an artery there might be an upfront risk, as was found in the original 30-day study, but over the long-term it would prove protective and eventually the stenting arm would catch up,” Dr. Grotta told Neurology Today. “But there wasn't even a signal, and the long-term analysis confirms the powerful effectiveness of aggressive medical therapy,” said Dr. Grotta, who served on the data monitoring team that ended the original trial but was not one of the investigators.
Dr. Grotta said the medical therapy in the context of the SAMMPRIS trial was assisted by a company that was specifically hired to provide the lifestyle modification and coaching. So success of medical therapy depends on a structured, systematic approach; he noted that many insurance companies are employing similar programs and offering beneficiaries incentives to participate.
He added that there may be some select, high-risk patients for whom stenting may be beneficial, or that stenting might be reserved for patients who fail aggressive medical therapy. “Just because the artery is narrowed may not be criteria for stenting,” he told Neurology Today. “It may be that we should look for an active plaque. We know in coronary disease that some stenosis is more malignant because of inflammation at the surface of the vessel. There are a number of factors one could conjecture pertinent to the vessel wall and physiology of the plague that might identify a higher risk patient.”
But Dr. Grotta also suggested that improvements in technique and technology could prove beneficial. “There are very tiny, fragile vessels. There may be other endovascular techniques we haven't developed that will prove useful. So we need to think outside the box,” said Dr. Grotta, who serves on the editorial advisory board of Neurology Today.