Does the Stenting Versus Aggressive Medical Therapy Trial Support Stenting for Subgroups With Intracranial Stenosis?
Background and Purpose—Although the Stenting Versus Aggressive Medical Therapy for Intracranial Arterial Stenosis (SAMMPRIS) trial showed that medical therapy alone was superior to stenting plus medical therapy for preventing recurrent strokes in patients with symptomatic intracranial stenosis, we determined whether SAMMPRIS supported the use of stenting in any subpopulations of patients with symptomatic intracranial arterial stenosis.
Methods—The primary outcome, 30-day stroke and death and later strokes in the territory of the qualifying artery, was compared in those with and without baseline factors in the 2 treatment arms, percutaneous transluminal angioplasty and stenting (PTAS) plus aggressive medical therapy versus aggressive medical therapy alone. Baseline factors included sex, age, race, diabetes mellitus, hypertension, lipid disorder, smoking status, type of qualifying event, qualifying event hypoperfusion symptoms, use of antithrombotic or proton pump inhibitor at baseline, days to enrollment, old infarcts in the same territory, percent stenosis, other artery stenosis, and location of the symptomatic artery.
Results—A total of 451 patients were enrolled, 227 randomized to aggressive medical therapy and 224 to PTAS. Of all variables evaluated, the observed 2-year event rates were higher with PTAS than with aggressive medical therapy in the vast majority and the interaction with treatment was not statistically significant for any of the factors.
Conclusions—The SAMMPRIS results do not provide evidence to support the use of PTAS using the Wingspan stent system compared with medical treatment in any examined subpopulation of patients with symptomatic intracranial stenosis, including those with qualifying event hypoperfusion symptoms.
The Stenting Versus Aggressive Medical Therapy for Intracranial Arterial Stenosis (SAMMPRIS) trial has shown that patients with a transient ischemic attack or stroke within 30 days before enrollment that was attributed to 70% to 99% stenosis of a major intracranial artery had greater benefit from Aggressive Medical Management alone (AMM) than with Percutaneous Transluminal Angioplasty and Stenting with the Wingspan stent plus Aggressive Medical Management (PTAS).1,2 This study determined whether there were subpopulations of patients with symptomatic intracranial arterial stenosis in whom SAMMPRIS did support the use of PTAS compared with AMM alone.
The study design for the SAMMPRIS trial has been published previously.3 AMM included antiplatelet therapy with clopidogrel 75 mg per day for 90 days and aspirin 325 mg per day indefinitely, careful risk factor management and a lifestyle modification program.3 Stenting was performed using the Wingspan stent system and patients treated with PTAS received the same AMM. All patients gave written informed consent to participate, and institutional review boards at all 50 participating sites in the United States approved the study protocol.
The primary outcome, 30-day stroke and death and later strokes in the territory of the qualifying artery, was compared in those with and without baseline factors in the 2 treatment arms, PTAS plus AMM versus AMM alone. Baseline factors are provided in the Table. Qualifying event hypoperfusion symptoms were defined as related to either change in position, effort on exertion or recent change in antihypertensive. Seven of these subgroups indicated by * had been prespecified.
The subgroup analyses were conducted by fitting a Cox proportional hazards regression model that included treatment, treatment by time to primary end point interaction (included because the proportional hazards assumption was not met for the treatments), the factor, and the treatment by factor interaction. P values are reported for the treatment by factor interaction and P<0.05 would indicate that the effect of treatment was different across the levels of the factor. Because the analysis results are intended to be exploratory, no adjustment was made for multiple subgroup comparisons. Kaplan–Meier estimates of the event rates by treatment at 2 years after randomization are reported for each of the factor levels.
Of 451 patients enrolled in SAMMPRIS, 227 were randomized to AMM and 224 to PTAS. The observed 2-year event rates were higher with PTAS than with AMM in the vast majority of variables evaluated and the interaction with treatment was not statistically significant for any of the factors (Table).
The results showed no differential effect of treatment with PTAS or AMM in any subgroup of patients with intracranial stenosis compared with the patients overall.
Previous studies have shown higher stroke recurrence rates in certain patient groups on medical treatment, such as those with a higher degree of stenosis and earlier time to enrollment4 or patients with clinical hemodynamic characteristics.5 Such risk groups did not show benefit with stenting in this study. In the 14% (31/227) of patients in this study that had qualifying event hypoperfusion symptoms in the AMM group, the 2-year probability of an outcome event was only 7.0%.
Although none of the baseline variables studied reached statistical significance for a treatment interaction, there was less of a numeric difference in the outcome between PTAS and AMM in some subgroups. These were patients with qualifying event hypoperfusion symptoms, blacks, those without a lipid disorder, smokers, and those with an old infarct in the territory of the stenotic vessel.
Limitations of this study included its post hoc nature and the small number of patients in some subgroups because SAMMPRIS did not reach its enrollment goal. These limitations raise the possibility of type I or type II errors for some subgroups (ie, erroneously concluding that there are differences in outcome between the 2 treatment arms or failing to identify a subgroup that benefits from medical therapy or stenting).
Given the results of this analysis and the fact that SAMMPRIS was stopped primarily for safety, there currently is no evidence to support the use of the Wingspan stent system in any group of patients with intracranial stenosis. The results continue to support the use of AMM in all examined subpopulations of patients with symptomatic intracranial stenosis.
Sources of Funding
Stenting Versus Aggressive Medical Therapy for Intracranial Arterial Stenosis (SAMMPRIS) is funded by the National Institute of Neurological Disorders and Stroke (NINDS) U01 NS058728. Stryker Neurovascular provided study devices and supplemental funding for third party device distribution, site monitoring, and study auditing and AstraZeneca donated rosuvastatin (Crestor) to study patients in the SAMMPRIS trial.
G.A. Cotsonis, M.J. Lynn, Drs Turan, Derdeyn, Fiorella, and M.I. Chimowitz received grant support from Stenting Versus Aggressive Medical Therapy for Intracranial Arterial Stenosis. L.S. Janis is the Program Director, NINDS. The other authors report no conflicts.
Guest Editor for this article was Sean Savitz, MD.
- Received April 30, 2015.
- Revision received August 21, 2015.
- Accepted August 26, 2015.
- © 2015 American Heart Association, Inc.
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