Rationale, Design, and Implementation of Aggressive Risk Factor Management in the Stenting and Aggressive Medical Management for Prevention of Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) Trial

• Authors: Tanya N. Turan, Medical University of South Carolina; Michael Lynn, Emory University; Azhar Nizam, Emory University; Bethany Lane, Emory University; Brent M. Egan, Medical University of South Carolina; Ngoc-Anh Le, Emory University; Maria F. Lopes-Virella, Medical University of South Carolina; Kathie L. Hermayer, Medical University of South Carolina; Oscar Benavente, University of British Columbia; Carole L. White, University of Texas Health Science Center; W. Virgil Brown, Emory University; Michelle F. Caskey, Medical University of South Carolina; Meghan R. Steiner, Medical University of South Carolina; Nicole Vilardo, Dartmouth College; Andrew Stufflebean, Medical University of South Carolina; Colin P. Derdeyn, Washington University in St. Louis; David Fiorella, State University of New York; Scott Janis, National Institute of Neurological Disorders and Stroke; Marc I. Chimowitz, Medical University of South Carolina
• Journal Title: Circulation: Cardiovascular Quality and Outcomes
• Volume: Volume 5, Number 5
• Publisher: American Heart Association | 2012-09-01, Pages E51-E60
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1161/CIRCOUTCOMES.112.966911
• Subjects: Biology, Neuroscience; Health Sciences, General
• Keywords: Science & Technology; Life Sciences & Biomedicine; Cardiac & Cardiovascular Systems; Cardiovascular System & Cardiology; stroke; cerebrovascular circulation; risk factors; atherosclerosis; lifestyle; TRANSIENT ISCHEMIC ATTACK; CORONARY-ARTERY-DISEASE; DENSITY-LIPOPROTEIN CHOLESTEROL; HEALTH-CARE PROFESSIONALS; HIGH-DOSE ATORVASTATIN; TREATMENT PANEL-III; CAROTID STENOSIS; DOUBLE-BLIND; CARDIOVASCULAR-DISEASE; PHYSICAL-ACTIVITY

Abstract

The value of comprehensive intensive atherosclerotic risk factor control in patients with coronary artery disease (CAD) is well-established. In 2007, the COURAGE trial demonstrated that among patients with stable coronary disease, intensive management of vascular risk factors was as good as endovascular intervention plus intensive medical management for preventing cardiac ischemic events1. Yet, despite the fact that atherosclerotic risk factor control in patients with stroke or TIA is recommended by guidelines2, a multimodal approach to prevention has not previously been tested in patients with atherosclerotic stroke. Older atherosclerotic-stroke prevention trials comparing carotid revascularization to medical therapy, such as NASCET3 and ACAS4, were performed in an era before statins and angiotensin converting enzyme (ACE) inhibitors became standard of care, and therefore risk factor control was not adequate by today’s standards. Even recent trials comparing carotid revascularization procedures5, 6 had little emphasis on risk factor control in their design and therefore had little impact on blood pressure and cholesterol measures at 1 year7, 8. Among stroke prevention trials in patients with heterogeneous causes of stroke, several trials have studied the effects of specific risk factor medications9–11 or of intensive control of a particular risk factor, such as blood pressure12, but no stroke prevention trials have used a muti-modal aggressive risk factor approach. Among patients with intracranial atherosclerosis, which may be the most common cause of stroke world-wide13, risk factor control is also believed to be important for stroke prevention. The Warfarin Aspirin Symptomatic Intracranial Disease (WASID) trial, in which patients with symptomatic intracranial stenosis were managed with either warfarin or aspirin and usual risk factor management14, showed that patients with poorly controlled blood pressure and elevated cholesterol during follow-up had significantly higher rates of recurrent stroke and other vascular events15, suggesting that aggressive management of vascular risk factors may benefit these patients. However, the impact of multi-modal aggressive risk factor control as a primary treatment strategy in patients with intracranial stenosis had not been assessed. Endovascular treatment of intracranial stenosis was also an emerging, yet unproven therapy. Therefore, in an effort to study these two treatment strategies, the Stenting and Aggressive Medical Management for Prevention of Recurrent stroke in Intracranial Stenosis (SAMMPRIS) Trial was designed to compare aggressive medical management alone versus aggressive medical management plus percutaneous transluminal angioplasty and stenting (PTAS). Thus, the SAMMPRIS trial became the first multicenter stroke prevention trial to encorporate multi-modal, protocol-driven risk factor control in the design. This paper focuses on the rationale, design, and implementation of the intensive risk factor management protocols in SAMMPRIS and describes challenges implementing these protocols during the trial and how the challenges have been managed.