R E V I E W Potential role of the endocannabinoid receptor antagonist rimonabant in the management of cardiometabolic risk: a narrative review of available data Kirk A Bronander1 Michael J Bloch2 1Division of General Internal Medicine, 2Divisions of Cardiology and General Internal Medicine, Department of Medicine, University of Nevada School of Medicine, Reno, NV, USA Correspondence: Kirk Bronander University of Nevada School of Medicine, m/s 355, Reno, NV 89557, USA Email kbronander@medicine.nevada.edu Abstract: The endocannabinoid system (ECS) is an endogenous physiological system com- posed of two cannabinoid receptors and several endogenous ligands. The ECS is intimately involved in appetite regulation and energy homeostasis, which makes it an intriguing target for pharmacological treatment of obesity, diabetes, and the metabolic syndrome. Rimonabant is the ﬁrst cannabinoid receptor (CB-1) antagonist being studied and utilized to treat obesity (it is approved in Europe but is currently under review in the United States). Large random- ized trials with rimonabant have demonstrated efﬁcacy in treatment of overweight and obese individuals with weight loss signiﬁcantly greater than a reduced calorie diet alone. In addition, multiple other cardiometabolic parameters were improved in the treatment groups including increased levels of high density lipoprotein cholesterol, reduced triglycerides, reduced waist circumference, improved insulin sensitivity, decreased insulin levels, and in diabetic patients improvement in glycosylated hemoglobin percentage. There was an increase in the adverse effects of depression, anxiety, irritability, and nausea in rimonabant-treated groups. This novel medication may become an important therapeutic option in the ﬁght to reduce cardiovascular disease worldwide through its unique action on cardiometabolic risk. Keywords: rimonabant, endocannabinoid, metabolic syndrome, obesity Introduction Despite important therapeutic advances, cardiovascular disease (CVD) remains the number one cause of death worldwide (World Health Organization 2006a). Traditional risk factors for cardiovascular disease include hypertension, dyslipidemia, smoking, family history of coronary disease, and aging. Major efforts have been made to identify and treat these risk factors with varying degrees of success. Most of the pharmacologi- cal advances that have been made in reducing cardiovascular risk are designed to treat individual traditional risk factors. Over the past decade, increasing evidence has implicated a number of emerging risk factors that also appear to independently identify patients at risk for CVD. The ever increasing list of emerging risk factors includes elevated triglycerides (TG), small low density lipoprotein cholesterol (LDL-C) particle size, insulin resistance and glucose intolerance, proinﬂammatory (as measured by high sensitivity c-reactive protein and other assays) states, and prothrombotic states (Grundy et al 2004). Many of these risks factors tend to cluster in individual patients compounding their risk of developing CVD. These same metabolic abnormalities also appear to predict the development of type 2 diabetes mellitus (T2DM). Both the National Cholesterol Edu- cation Program’s (NCEP) Adult Treatment Panel III and the World Health Organiza- tion (WHO) have recognized this clustering of risk factors in their deﬁnitions of the Vascular Health and Risk Management 2007:3(2) 181–190 © 2007 Dove Medical Press Limited. All rights reserved 181