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Effect of rimonabant on progression of atherosclerosis in patients with abdominal obesity and coronary artery disease: the STRADIVARIUS randomized controlled trial.
JAMA. 2008 Apr 02; 299(13):1547-60.JAMA

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.

Authors+Show Affiliations

Department of Cardiovascular Medicine and Cleveland Clinic Lerner School of Medicine, Cleveland, Ohio, USA. nissens@ccf.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18387931

Citation

Nissen, Steven E., et al. "Effect of Rimonabant On Progression of Atherosclerosis in Patients With Abdominal Obesity and Coronary Artery Disease: the STRADIVARIUS Randomized Controlled Trial." JAMA, vol. 299, no. 13, 2008, pp. 1547-60.
Nissen SE, Nicholls SJ, Wolski K, et al. Effect of rimonabant on progression of atherosclerosis in patients with abdominal obesity and coronary artery disease: the STRADIVARIUS randomized controlled trial. JAMA. 2008;299(13):1547-60.
Nissen, S. E., Nicholls, S. J., Wolski, K., Rodés-Cabau, J., Cannon, C. P., Deanfield, J. E., Després, J. P., Kastelein, J. J., Steinhubl, S. R., Kapadia, S., Yasin, M., Ruzyllo, W., Gaudin, C., Job, B., Hu, B., Bhatt, D. L., Lincoff, A. M., & Tuzcu, E. M. (2008). Effect of rimonabant on progression of atherosclerosis in patients with abdominal obesity and coronary artery disease: the STRADIVARIUS randomized controlled trial. JAMA, 299(13), 1547-60. https://doi.org/10.1001/jama.299.13.1547
Nissen SE, et al. Effect of Rimonabant On Progression of Atherosclerosis in Patients With Abdominal Obesity and Coronary Artery Disease: the STRADIVARIUS Randomized Controlled Trial. JAMA. 2008 Apr 2;299(13):1547-60. PubMed PMID: 18387931.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of rimonabant on progression of atherosclerosis in patients with abdominal obesity and coronary artery disease: the STRADIVARIUS randomized controlled trial. AU - Nissen,Steven E, AU - Nicholls,Stephen J, AU - Wolski,Kathy, AU - Rodés-Cabau,Josep, AU - Cannon,Christopher P, AU - Deanfield,John E, AU - Després,Jean-Pierre, AU - Kastelein,John J P, AU - Steinhubl,Steven R, AU - Kapadia,Samir, AU - Yasin,Muhammad, AU - Ruzyllo,Witold, AU - Gaudin,Christophe, AU - Job,Bernard, AU - Hu,Bo, AU - Bhatt,Deepak L, AU - Lincoff,A Michael, AU - Tuzcu,E Murat, AU - ,, Y1 - 2008/04/01/ PY - 2008/4/5/pubmed PY - 2008/4/9/medline PY - 2008/4/5/entrez SP - 1547 EP - 60 JF - JAMA JO - JAMA VL - 299 IS - 13 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. SN - 1538-3598 UR - https://www.unboundmedicine.com/medline/citation/18387931/Effect_of_rimonabant_on_progression_of_atherosclerosis_in_patients_with_abdominal_obesity_and_coronary_artery_disease:_the_STRADIVARIUS_randomized_controlled_trial_ L2 - https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.299.13.1547 DB - PRIME DP - Unbound Medicine ER -