Stenting may do more harm than good in patients with intracranial arterial stenosis who receive aggressive medical management, investigators reported in the September 15 New England Journal of Medicine.
“Patients with symptomatic intracranial stenosis should be treated with aggressive medical therapy alone,” lead author Marc I. Chimowitz, MBChB, Professor of Neurology and Associate Dean of Faculty Development at the Medical University of South Carolina, Charleston, told Neurology Reviews. According to Chimowitz, stenting should be abandoned “for the majority of patients with intracranial arterial stenosis, at least until alternative endovascular treatments have been shown in clinical trials to be more effective than aggressive medical therapy, which will be hard to achieve given the relatively low rate of stroke on aggressive medical therapy in this trial.”
Percutaneous transluminal angioplasty and stenting (PTAS), an increasingly popular treatment for intracranial arterial stenosis, has been available since 2005 for patients who have 50% to 99% stenosis and experienced a transient ischemic attack (TIA) or stroke while receiving antithrombotic therapy. However, no previous trials have compared the treatment’s outcomes with those of aggressive medical management of the stenosis.
SAMMPRIS Trial Results
The Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) is an NIH-funded trial in which investigators followed the outcomes of both treatment options in a cohort of 451 patients, all of whom had experienced a TIA or a nondisabling stroke due to stenosis of 70% to 99% of the diameter of a major intracranial artery within 30 days prior to enrollment. Of these patients, 227 were randomized to aggressive medical management alone and 224 were randomized to receive this management in combination with PTAS. The aggressive medical management consisted of aspirin 325 mg daily, clopidogrel 75 mg daily for 90 days after enrollment, and management of primary risk factors (elevated blood pressure and elevated low-density lipoprotein) and secondary risk factors (diabetes, smoking, non–high-density lipoprotein, excess weight, and lack of exercise).
The study’s primary end point was stroke or death within 30 days after enrollment or after a revascularization procedure for the qualifying lesion during the follow-up period or ischemic stroke in the territory of the qualifying artery between day 31 and the end of the follow-up period.
Enrollment Ended Early
Within 30 days after enrollment, the primary end point occurred in 33 patients in the PTAS group (14.7%), compared with only 13 patients in the medical-management alone group (5.8%). Of the events in the PTAS group, 12.5% were nonfatal strokes and 2.2% were fatal strokes, and of the events in the medical- management group, 5.3% were nonfatal strokes and one (0.4%) was a death unrelated to stroke. Symptomatic brain hemorrhages accounted for 10 of the 33 strokes in the PTAS group (30.3%) but none of the 12 strokes in the medical-management group. Twenty-five of the 33 strokes in the PTAS group (75.7%) occurred within one day after the procedure, while eight (24.2%) occurred two to six days later.
One-year rates of the primary end point were 20.0% in the PTAS group and 12.2% in the medical-management group. The researchers saw the same result when they excluded 11 patients in the PTAS group who did not undergo angioplasty or stenting and nine patients in the medical-management group who underwent PTAS during follow-up.
Enrollment of new patients was stopped due to concerns about the safety of PTAS and because futility analyses indicated virtually no chance of a benefit from the treatment by the end of the follow-up period. The investigators plan to follow already enrolled patients for an additional two years to determine the treatment’s long-term effects, however.
Explaining the Differences
The medical-management group’s advantage was driven both by its lower-than-estimated rate of stroke and by the PTSA group’s higher-than-expected rate of stroke. Stenting registries have described 30-day rates of stroke or death of 4.4% to 9.6%, and a previous trial showed a 30-day rate of stroke or death of 10.7% with aspirin or warfarin.
The SAMMPRIS trial’s focus on patients with recent symptoms may have influenced the higher rate of perioperative events, as recent symptoms may indicate unstable plaque that can become dislodged during PTAS and increase the risk of distal embolism, according to the researchers. However, Dr. Chimowitz added, “Stenting should not be performed in patients with more remote symptoms, either. These patients are at a relatively low risk of stroke on usual medical management, and they are likely to be at an even lower risk on aggressive medical therapy.”
Joseph P. Broderick, MD, of the University of Cincinnati College of Medicine, added in an accompanying editorial that almost one-third of all perioperative strokes were accounted for by symptomatic intracranial hemorrhages, which are believed to result from reperfusion hemorrhage or subarachnoid hemorrhage from wire manipulations during stenting. “This latter complication emphasizes the fact that stenting of the intracranial vasculature is technically more challenging than is stenting of the extracranial carotid artery,” he said.