Nissen SE et al. (2008) Effect of rimonabant on progression of atherosclerosis in patients with abdominal obesity and coronary artery disease: the STRADIVARIUS randomized controlled trial. JAMA 299: 1547–1560

Abdominal adiposity and the metabolic syndrome are associated with an increased risk of atherosclerotic cardiovascular disease. Inhibition of cannabinoid type 1 (CB1) receptors suppresses appetite and can ameliorate some features of the metabolic syndrome that are associated with abdominal obesity (dyslipidemia, inflammatory markers, glycemia). Nissen and colleagues investigated whether treatment with one such CB1 antagonist, rimonabant, could slow the progression of coronary atherosclerosis in obese patients with the metabolic syndrome.

The STRADIVARIUS multicenter trial enrolled patients (average age <60 years) with pre-existing coronary disease and abdominal obesity and those who met criteria for the metabolic syndrome or were current smokers. Patients received 20 mg rimonabant or placebo daily for 18–20 months, together with dietary advice to achieve a moderately hypocaloric diet. A total of 676 patients underwent intravascular ultrasonography of the coronary arteries at both baseline and at the end of follow-up.

Weight loss and reduction in waist circumference were greater in patients treated with rimonabant than those receiving placebo. Rimonabant treatment elevated HDL cholesterol levels by 22.4% and reduced triglyceride levels by 20.5%, demonstrating the capacity of the CB1 antagonist to reverse some effects of the metabolic syndrome. Rimonabant treatment did not significantly slow the rate of progression of atherosclerosis; however, this therapy did reduce patients' total atheroma volume. Rimonabant was also associated with adverse psychiatric events.

Although the authors expected a greater reduction in the progression of atherosclerosis, they believe that managing coronary disease by treatment of obesity using CB1 inhibition warrants further study.