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

The value of comprehensive intensive atherosclerotic risk factor control in patients with coronary artery disease is well established. In 2007, the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (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 events.1 Yet, despite the fact that atherosclerotic risk factor control in patients with stroke or transient ischemic attack is recommended by guidelines,2 a multimodal approach to prevention has not previously been tested in patients with atherosclerotic stroke. Older atherosclerotic stroke prevention trials comparing carotid revascularization with medical therapy, such as North American Symptomatic Carotid Endarterectomy Trial (NASCET)3 and Asymptomatic Carotid Atherosclerosis Study (ACAS),4 were performed in an era before statins and angiotensin converting enzyme 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 year.7,8 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 pressure,12 but no stroke prevention trials have used a mutimodal aggressive risk factor approach. Among patients with intracranial atherosclerosis, which may be the most common cause of stroke worldwide,13 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 management,14 showed that …