CINCINNATI—Unique challenges associated with revascularization for blocked intracranial arteries for preventing and treating stroke make aggressive medical therapy alone a preferable alternative for many patients with a recent transient ischemic attack or stroke, a University of Cincinnati (UC) neurologist writes in the New England Journal of Medicine (NEJM).
Joseph Broderick, MD, Albert Barnes Voorheis Chair of Neurology at UC and a UC Health neurologist, wrote the editorial to accompany an article, "Stenting versus Aggressive Medical Therapy for Intracranial Artery Stenosis.” Both the article and the editorial appear in NEJM’s Online First publication Sept. 7, 2011, and are scheduled for the Sept. 15 print issue.
The article recounted results of the SAMMPRIS (Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis) trial, which was funded by the National Institutes of Health (NIH) and began recruiting patients in 2008. It ended in April 2011 after the National Institute of Neurological Disorders and Stroke (NINDS) issued a clinical alert to stop enrollment.
Pooja Khatri, MD, of the UC neurology department and UC Health Neurology, and Andrew Ringer, MD, of the UC neurosurgery department and Mayfield Clinic, were the principal investigators at the UC site. Broderick, research director at the UC Neuroscience Institute, was not an investigator in the SAMMPRIS trial. (Khatri and Ringer are also members of the UC Neuroscience Institute.)
The SAMMPRIS trial compared aggressive medical therapy, including two antiplatelet medications (clopidogrel and aspirin) combined with intracranial angioplasty and the Wingspan stent, manufactured by Boston Scientific, with aggressive medical therapy alone for patients who had a recent transient ischemic attack or stroke attributed to a major stenosis (narrowing) of a major intracranial artery.
A transient ischemic attack is a temporary loss of blood supply to the brain, usually caused by a blockage such as a clot. A stent is a mechanical device used to hold a vessel or artery open.
Enrollment in the trial was stopped prematurely because 14.7 percent of 451 patients (out of a planned 764) who received the stent had a stroke or died by 30 days after randomization, as compared with 5.8 percent of patients treated with aggressive medical therapy alone.
"Stenting of the intracranial vasculature is technically more challenging than is stenting of the extracranial carotid artery because of the tortuous course of the internal carotid artery through bony canals, an abrupt right-angle turn for the middle cerebral artery, and smaller arterial diameters. Small, penetrating brain arteries from the trunks of the middle cerebral and basilar arteries are often near or at the site of the placement of the stent and may be compromised,” Broderick points out in the editorial.
"These anatomical and physiological differences … highlight the point that it is not just the safety of a given device, but the safety of the procedure itself, that must be considered.”
Broderick, who noted in the editorial that the SAMMPRIS trial was the third randomized trial of intracranial revascularization that failed to show a benefit over aggressive medical therapy alone for prevention of stroke, says there are risks associated with any interventional procedure, which in the case of stenting may include inadvertently damaging the artery.
"If you could completely get rid of all that up-front risk associated with the procedure, then the stent would probably provide an overall benefit,” he said. "But if the up-front risk fails to justify the amount of strokes you prevent in the long term, then it’s not a good trade.”
A key lesson from the SAMMPRIS trial, Broderick wrote, is that "aggressive and attentive medical therapy is an effective approach to the prevention of stroke in high-risk populations.”
In addition to antiplatelet medications, Broderick says, "such therapy would include carefully controlling the blood pressure, a statin medication, managing diabetes, refraining from smoking, diet and exercise.”
In some individual cases where aggressive medical therapy fails and the patient has recurrent incapacitating symptoms, he adds, a revascularization procedure could be considered. But generally speaking, the results of the SAMMPRIS trial and previous studies "greatly limit the patients we’d be referring for this procedure at this point in time.”
Still, Broderick wrote, the search for stroke prevention technology should continue:
"New technology for preventing and treating stroke should be tested in trials that address clinical effectiveness and incorporate the best current medical management of stroke,” he wrote.