title: Effect of rimonabant on progression of atherosclerosis in patients with abdominal obesity and coronary artery disease: the STRADIVARIUS randomized controlled trial.
abstract: BACKGROUND
  Abdominal obesity is associated with metabolic abnormalities and increased risk of atherosclerotic cardiovascular disease. However, no obesity management strategy has demonstrated the ability to slow progression of coronary disease.
  
  
  OBJECTIVE
  To determine whether weight loss and metabolic effects of the selective cannabinoid type 1 receptor antagonist rimonabant reduces progression of coronary disease in patients with abdominal obesity and the metabolic syndrome.
  
  
  METHODS
  Randomized, double-blinded, placebo-controlled, 2-group, parallel-group trial (enrollment December 2004-December 2005) comparing rimonabant with placebo in 839 patients at 112 centers in North America, Europe, and Australia.
  
  
  METHODS
  Patients received dietary counseling, were randomized to receive rimonabant (20 mg daily) or matching placebo, and underwent coronary intravascular ultrasonography at baseline (n = 839) and study completion (n = 676).
  
  
  METHODS
  The primary efficacy parameter was change in percent atheroma volume (PAV); the secondary efficacy parameter was change in normalized total atheroma volume (TAV).
  
  
  RESULTS
  In the rimonabant vs placebo groups, PAV (95% confidence interval [CI]) increased 0.25% (-0.04% to 0.54%) vs 0.51% (0.22% to 0.80%) (P = .22), respectively, and TAV decreased 2.2 mm3 (-4.09 to -0.24) vs an increase of 0.88 mm3 (-1.03 to 2.79) (P = .03). In the rimonabant vs placebo groups, imputing results based on baseline characteristics for patients not completing the trial, PAV increased 0.25% (-0.04% to 0.55%) vs 0.57% (0.29% to 0.84%) (P = .13), and TAV decreased 1.95 mm3 (-3.8 to -0.10) vs an increase of 1.19 mm3 (-0.73 to 3.12) (P = .02). Rimonabant-treated patients had a larger reduction in body weight (4.3 kg [-5.1 to -3.5] vs 0.5 kg [-1.3 to 0.3]) and greater decrease in waist circumference (4.5 cm [-5.4 to -3.7] vs 1.0 cm [-1.9 to -0.2]) (P < .001 for both comparisons). In the rimonabant vs placebo groups, high-density lipoprotein cholesterol levels increased 5.8 mg/dL (4.9 to 6.8) (22.4%) vs 1.8 mg/dL (0.9 to 2.7) (6.9%) (P < .001), and median triglyceride levels decreased 24.8 mg/dL (-35.4 to -17.3) (20.5%) vs 8.9 mg/dL (-14.2 to -1.8) (6.2%) (P < .001). Rimonabant-treated patients had greater decreases in high-sensitivity C-reactive protein (1.3 mg/dL [-1.7 to -1.2] [50.3%] vs 0.9 mg/dL [-1.4 to -0.5] [30.9%]) and less increase in glycated hemoglobin levels (0.11% [0.02% to 0.20%] vs 0.40% [0.31% to 0.49%]) (P < .001 for both comparisons). Psychiatric adverse effects were more common in the rimonabant group (43.4% vs 28.4%, P < .001).
  
  
  CONCLUSIONS
  After 18 months of treatment, the study failed to show an effect for rimonabant on disease progression for the primary end point (PAV) but showed a favorable effect on the secondary end point (TAV). Determining whether rimonabant is useful in management of coronary disease will require additional imaging and outcomes trials, which are currently under way.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00124332.
authors.affiliation: Department of Cardiovascular Medicine and Cleveland Clinic Lerner School of Medicine, Cleveland, Ohio, USA. nissens@ccf.org
authors.forename: Steven E
authors.initials: SE
authors.lastname: Nissen
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Nicholls
authors.forename: Kathy
authors.initials: K
authors.lastname: Wolski
authors.forename: Josep
authors.initials: J
authors.lastname: Rodés-Cabau
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Cannon
authors.forename: John E
authors.initials: JE
authors.lastname: Deanfield
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Després
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: Steven R
authors.initials: SR
authors.lastname: Steinhubl
authors.forename: Samir
authors.initials: S
authors.lastname: Kapadia
authors.forename: Muhammad
authors.initials: M
authors.lastname: Yasin
authors.forename: Witold
authors.initials: W
authors.lastname: Ruzyllo
authors.forename: Christophe
authors.initials: C
authors.lastname: Gaudin
authors.forename: Bernard
authors.initials: B
authors.lastname: Job
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.forename: Deepak L
authors.initials: DL
authors.lastname: Bhatt
authors.forename: A Michael
authors.initials: AM
authors.lastname: Lincoff
authors.forename: E Murat
authors.initials: EM
authors.lastname: Tuzcu
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000000981:diagnostic imaging / Q000517:prevention & control*; D003324:Coronary Artery Disease / Q000150:complications* / Q000188:drug therapy; D003331:Coronary Vessels / Q000000981:diagnostic imaging; D004038:Diet, Reducing; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000503:physiopathology / Q000628:therapy*; D008875:Middle Aged; D009765:Obesity / Q000150:complications* / Q000178:diet therapy; D010880:Piperidines / Q000627:therapeutic use*; D011446:Prospective Studies; D011720:Pyrazoles / Q000627:therapeutic use*; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*; D000077285:Rimonabant; D018084:Ultrasonography, Interventional
chemical_list: D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D000077285:Rimonabant