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

Steven E. Nissen, Stephen J. Nicholls, Kathy Wolski, Josep Rodés-Cabau, Christopher P. Cannon, John E. Deanfield, Jean Pierre Després, John J P Kastelein, Steven R. Steinhubl, Samir Kapadia, Muhammad Yasin, Witold Ruzyllo, Christophe Gaudin, Bernard Job, Bo Hu, Deepak L. Bhatt, A. Michael Lincoff, E. Murat Tuzcu

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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 2.2mm3 (-4.09 to -0.24) vs an increase of 0.88mm3 (-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 1.95mm3 (-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 5.8mg/dL (4.9 to 6.8) (22.4%) vs 1.8mg/dL (0.9 to 2.7) (6.9%) (P<.001), and median triglyceride levels decreased 24.8mg/dL (-35.4 to -17.3) (20.5%) vs 8.9mg/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.

LanguageEnglish
Pages1547-1560
Number of pages14
JournalJAMA - Journal of the American Medical Association
Volume299
Issue number13
DOIs
Publication statusPublished - 2 Apr 2008

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Nissen, Steven E. ; Nicholls, Stephen J. ; Wolski, Kathy ; Rodés-Cabau, Josep ; Cannon, Christopher P. ; Deanfield, John E. ; Després, Jean Pierre ; Kastelein, John J P ; Steinhubl, Steven R. ; Kapadia, Samir ; Yasin, Muhammad ; Ruzyllo, Witold ; Gaudin, Christophe ; Job, Bernard ; Hu, Bo ; Bhatt, Deepak L. ; Lincoff, A. Michael ; Tuzcu, E. Murat. / Effect of rimonabant on progression of atherosclerosis in patients with abdominal obesity and coronary artery disease : The STRADIVARIUS randomized controlled trial. In: JAMA - Journal of the American Medical Association. 2008 ; Vol. 299, No. 13. pp. 1547-1560.
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title = "Effect of rimonabant on progression of atherosclerosis in patients with abdominal obesity and coronary artery disease: The STRADIVARIUS randomized controlled trial",
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 2.2mm3 (-4.09 to -0.24) vs an increase of 0.88mm3 (-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 1.95mm3 (-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 5.8mg/dL (4.9 to 6.8) (22.4{\%}) vs 1.8mg/dL (0.9 to 2.7) (6.9{\%}) (P<.001), and median triglyceride levels decreased 24.8mg/dL (-35.4 to -17.3) (20.5{\%}) vs 8.9mg/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.",
author = "Nissen, {Steven E.} and Nicholls, {Stephen J.} and Kathy Wolski and Josep Rod{\'e}s-Cabau and Cannon, {Christopher P.} and Deanfield, {John E.} and Despr{\'e}s, {Jean Pierre} and Kastelein, {John J P} and Steinhubl, {Steven R.} and Samir Kapadia and Muhammad Yasin and Witold Ruzyllo and Christophe Gaudin and Bernard Job and Bo Hu and Bhatt, {Deepak L.} and Lincoff, {A. Michael} and Tuzcu, {E. Murat}",
year = "2008",
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Nissen, SE, Nicholls, SJ, Wolski, K, Rodés-Cabau, J, Cannon, CP, Deanfield, JE, Després, JP, Kastelein, JJP, Steinhubl, SR, Kapadia, S, Yasin, M, Ruzyllo, W, Gaudin, C, Job, B, Hu, B, Bhatt, DL, Lincoff, AM & Tuzcu, EM 2008, 'Effect of rimonabant on progression of atherosclerosis in patients with abdominal obesity and coronary artery disease: The STRADIVARIUS randomized controlled trial', JAMA - Journal of the American Medical Association, vol. 299, no. 13, pp. 1547-1560. https://doi.org/10.1001/jama.299.13.1547

Effect of rimonabant on progression of atherosclerosis in patients with abdominal obesity and coronary artery disease : The STRADIVARIUS randomized controlled trial. / Nissen, Steven E.; Nicholls, Stephen J.; Wolski, Kathy; Rodés-Cabau, Josep; Cannon, Christopher P.; Deanfield, John E.; Després, Jean Pierre; Kastelein, John J P; Steinhubl, Steven R.; Kapadia, Samir; Yasin, Muhammad; Ruzyllo, Witold; Gaudin, Christophe; Job, Bernard; Hu, Bo; Bhatt, Deepak L.; Lincoff, A. Michael; Tuzcu, E. Murat.

In: JAMA - Journal of the American Medical Association, Vol. 299, No. 13, 02.04.2008, p. 1547-1560.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effect of rimonabant on progression of atherosclerosis in patients with abdominal obesity and coronary artery disease

T2 - JAMA : the journal of the American Medical Association

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

PY - 2008/4/2

Y1 - 2008/4/2

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 2.2mm3 (-4.09 to -0.24) vs an increase of 0.88mm3 (-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 1.95mm3 (-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 5.8mg/dL (4.9 to 6.8) (22.4%) vs 1.8mg/dL (0.9 to 2.7) (6.9%) (P<.001), and median triglyceride levels decreased 24.8mg/dL (-35.4 to -17.3) (20.5%) vs 8.9mg/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.

AB - 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 2.2mm3 (-4.09 to -0.24) vs an increase of 0.88mm3 (-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 1.95mm3 (-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 5.8mg/dL (4.9 to 6.8) (22.4%) vs 1.8mg/dL (0.9 to 2.7) (6.9%) (P<.001), and median triglyceride levels decreased 24.8mg/dL (-35.4 to -17.3) (20.5%) vs 8.9mg/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.

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