NEJM: Medical therapy bests stenting at preventing high-risk strokes
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“There were two unexpected findings in this trial,” Marc. I Chimowitz, MB, ChB, of the Medical University of South Carolina Stroke Program in Charleston, S.C., told Cardiovascular Business. “One was that the rate of stroke after stenting was much higher than we estimated it to be. That was the bad news. The good news was the aggressive medical management, with therapies like statins and the combination of aspirin and clopidogrel, appear to be quite effective for stroke prevention in this population.”
Atherosclerotic intracranial arterial stenosis is a common cause of stroke, and patients with 70 percent to 90 percent stenosis are at high risk of a second stroke. Two strategies have been used to treat these high-risk patients: PTAS, and medical management that combines platelet therapy with management of risk factors.
Chimowitz and colleagues designed the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial to compare PTAS plus aggressive medical management with aggressive medical management alone in high-risk patients. Identical aggressive medical management in both groups included aspirin, clopidogrel (Plavix, Bristol Myers-Squibb/Senofi Aventis), management of primary risk factors such as cholesterol levels and blood pressure and a lifestyle modification program.
They enrolled 451 patients who had a recent transient ischemic attack (TIA) or stroke attributed to stenosis of 70 percent to 99 percent of the diameter of a major intracranial artery and randomly assigned them to the PTAS with the use of the Wingspan stent system plus therapy group (224 patients) or the therapy group (227 patients). The primary endpoint was death at 30 days or less, revascularization or stroke beyond 30 days.
“The subgroup we chose was the highest-risk population who we thought would most likely benefit from stenting,” Chimowitz said. “As it turned out, we found the opposite.”
The PTAS group had a 30-day rate of stroke or death of 14.7 percent, much higher than the 5.8 percent found in the medical management group. Thirteen patients in each group experienced nonfatal ischemic strokes in the area of the qualifying artery. Researchers calculated the one-year rate of a primary endpoint occurring at 20 percent in the PTAS group and 12.2 percent in the medical management group.
Enrollment in the trial closed in April when early data indicated that stenting was associated with more strokes and death. Chimowitz and colleagues noted that evaluations at the conclusion of the trial should further elucidate long-term outcomes. “[F]ewer than half of the patients have been followed for longer than one year,” the authors wrote. “Therefore, continued follow-up of the patients who are currently enrolled will be important to determine the long-term outcome in the two groups.
“Among the patients receiving medical management only, progression of stenosis may occur over time that could result in a stroke from a distal embolism or hypoperfusion. Among patients in whom a stent has been placed, restenosis occurs in 25 to 30 percent within six months after intracranial PTAS and could also lead to later stroke.”
The authors reiterated that current results showed aggressive medical therapy was superior to PTAS with the Wingspan stent system and concluded that the strategy could be duplicated in clinical practice. “The cornerstone of medical management is aspirin, clopidogrel, management of LDL and blood pressure,” Chimowitz said. “While many people will think the medical management strategy we used in this trial is pie in the sky, it actually is not that hard to do.”
In an accompanying NEJM editorial, Joseph P. Broderick, MD, of the University of Cincinnati College of Medicine in Cincinnati, wrote that the SAMMPRIS results highlighted three lessons. He pointed out that intracranial revascularization was more challenging than revascularization of extracranial carotid stenosis; aggressive medical therapy was effective at preventing stroke in high-risk patients; and federal agencies play a role in the advancement of cost-effective care.
“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,” Broderick wrote. “The FDA and CMS [Centers for Medicare & Medicaid Services] must be consistent gatekeepers for the distribution and diffusion into clinical practice of technology that affects the quality and cost of clinical care.”