Effect of rimonabant on progression of atherosclerosis in patients with abdominal obesity and coronary artery disease: the STRADIVARIUS randomized controlled trial.

@article{citeulike:2682758, abstract = {CONTEXT: 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. DESIGN, SETTING, AND PATIENTS: 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. INTERVENTIONS: 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). MAIN OUTCOME MEASURES: 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. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00124332.}, address = {Department of Cardiovascular Medicine and Cleveland Clinic Lerner School of Medicine, Cleveland, Ohio, USA. nissens@ccf.org}, author = {Nissen, S. E. and Nicholls, S. J. and Wolski, K. and Rod\'{e}s-Cabau, J. and Cannon, C. P. and Deanfield, J. E. and Despr\'{e}s, J. P. and Kastelein, J. J. and Steinhubl, S. R. and Kapadia, S. and Yasin, M. and Ruzyllo, W. and Gaudin, C. and Job, B. and Hu, B. and Bhatt, D. L. and Lincoff, A. M. and Tuzcu, E. M. and }, citeulike-article-id = {2682758}, doi = {http://dx.doi.org/10.1001/jama.299.13.1547}, issn = {1538-3598}, journal = {JAMA : the journal of the American Medical Association}, keywords = {chd, metabolic-syndrome, rct, vasculardisease}, month = {April}, number = {13}, pages = {1547--1560}, posted-at = {2008-04-17 17:03:10}, priority = {2}, title = {Effect of rimonabant on progression of atherosclerosis in patients with abdominal obesity and coronary artery disease: the STRADIVARIUS randomized controlled trial.}, url = {http://dx.doi.org/10.1001/jama.299.13.1547}, volume = {299}, year = {2008} }

TY - JOUR ID - citeulike:2682758 L3 - citeulike-article-id:2682758 TI - Effect of rimonabant on progression of atherosclerosis in patients with abdominal obesity and coronary artery disease: the STRADIVARIUS randomized controlled trial. JF - JAMA : the journal of the American Medical Association VL - 299 IS - 13 SP - 1547 EP - 1560 AD - Department of Cardiovascular Medicine and Cleveland Clinic Lerner School of Medicine, Cleveland, Ohio, USA. nissens@ccf.org SN - 1538-3598 N2 - CONTEXT: 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. DESIGN, SETTING, AND PATIENTS: 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. INTERVENTIONS: 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). MAIN OUTCOME MEASURES: 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. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00124332. KW - chd KW - metabolic-syndrome KW - rct KW - vasculardisease AU - Nissen, SE AU - Nicholls, SJ AU - Wolski, K AU - Rodés-Cabau, J AU - Cannon, CP AU - Deanfield, JE AU - Després, JP AU - Kastelein, JJ AU - Steinhubl, SR AU - Kapadia, S AU - Yasin, M AU - Ruzyllo, W AU - Gaudin, C AU - Job, B AU - Hu, B AU - Bhatt, DL AU - Lincoff, AM AU - Tuzcu, EM PY - 2008/04/02/ UR - http://dx.doi.org/10.1001/jama.299.13.1547 ER -