Factors Associated With Recurrent Ischemic Stroke in the Medical Group of the SAMMPRIS Trial

Abstract

Importance: The Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) Trial showed that aggressive medical therapy was more effective than stenting for preventing stroke in patients with symptomatic intracranial stenosis. However, 15% of patients in the medical group still experienced a primary end point during a median follow-up of 32.7 months.

Objective: To determine baseline features that were associated with a high rate of a primary end point in the medical arm of the SAMMPRIS Trial.

Design, setting, and participants: A post hoc analysis of patients in the medical arm only of the SAMMPRIS trial. Enrollment occurred between October 2008 and April 2013 and included 227 patients randomized to medical management alone. Baseline demographic features, vascular risk factors, qualifying event, brain imaging, and angiographic features were analyzed. Bivariate and multivariable proportional hazard regression modeling was performed to relate baseline features to the time until a primary end point. The post hoc analysis was conducted from November 2014 to June 2015.

Interventions: The SAMMPRIS Trial compared stenting with aggressive medical management in patients with a stroke or transient ischemic attack attributed to 70% to 99% stenosis of a major intracranial artery.

Main outcomes and measures: The primary outcome was any of the following: stroke or death within 30 days of enrollment, ischemic stroke in the territory of the symptomatic intracranial artery beyond 30 days after enrollment, or any stroke or death within 30 days after stenting a patient in the medical group during follow-up.

Results: A total of 227 patients were included in the study, 82 of whom were female, and the mean (SD) age was 59.5 (11.8) years. Being female (hazard ratio [HR], 1.9; 95% CI, 0.96-3.7), having diabetes mellitus (HR, 1.8; 95% CI, 0.9-3.5), not taking a statin at enrollment (HR, 2.6; 95% CI, 1.2-5.7), stroke as the qualifying event (HR, 2.5; 95% CI, 1.03-6.0), Rankin grade of 1 or greater (HR, 2.3; 95% CI, 0.9-5.5), old infarct in the territory of the stenotic artery (HR, 2.6; 95% CI, 1.3-5.1), and greater than 80% stenosis (HR, 1.9; 95% CI, 0.9-3.7) were associated (P < .10) with higher risk on bivariate analysis. Factors that were significantly associated with a primary end point on multivariable analyses were old infarct in the territory (HR, 2.6; 95% CI, 1.3-5.3; P = .006), stroke as the qualifying event (HR, 3.0; 95% CI, 1.1-7.7; P = .03), and no statin use at enrollment (HR, 2.4; 95% CI, 1.1-5.2; P = .03).

Conclusions and relevance: Old infarct in the territory of the stenosis, new stroke presentation, and absence of statin use at enrollment were independently associated with high rates of the primary end point in the medical group in the SAMMPRIS Trial. These features may be useful for selecting high-risk patients for future clinical trials evaluating alternative therapies for intracranial stenosis.

Trial registration: clinicaltrials.gov Identifier: NCT00576693.

Conflict of interest statement

Conflict of Interest Disclosures: DrWaters has received fees as a medical expert in medical legal cases unrelated to this research. Dr Turan has received support from AstraZeneca and Stryker Neurovascular related to this study, other support from CardioNet (consultant), personal fees from Gore and Boehringer Ingelheim for participating as a stroke adjudicator in clinical trials unrelated to this work, and personal fees as an expert witness in medical legal cases unrelated to this research. Dr Derdeyn has relationships with companies that manufacture medical devices for the treatment of cerebrovascular disease in general, although none directly involved in this study. These includeW. L. Gore and Associates (scientific advisory board and consultant), MicroVention Inc (Angiographic Core Lab for clinical trial), Penumbra Inc (data and safety monitoring board member for clinical trial), and Pulse Therapeutics (chair, scientific advisory board). Dr Fiorella has received payment for research/salary support from Siemens, MicroVention, and Sequent Medical; consulting fees from Covidien/Ev3, Codman and Shurtleff, and Penumbra; royalties from Codman and Shurtleff (REVIVE); and ownership and stock interests in Vascular Simulators LLC, TDC Technologies, and CVSL.MsMontgomery has received fees from MicroVention Inc as a consultant. Dr Chimowitz has received support from AstraZeneca and Stryker Neurovascular (formerly Boston Scientific Neurovascular) related to this study. He also reports personal fees from Gore Associates, Merck /Parexel, and Medtronic for participating as a stroke adjudicator or data safety monitoring board member on clinical trials unrelated to the submittedwork. He also reports personal fees as an expertwitness in medical legal cases related to stroke. No other disclosures were reported.

Figures

Figure

Cumulative Probability of Primary End Point vs Time Since Randomization