Rimonabant does not reduce atherosclerosis progression in STRADIVARIUS

April 1, 2008 By Vijayalakshmi Kunadian MBBS MD MRCP [mailto:vkunadian@perfuse.org]

ACC 08-Chicago, IL: Treatment of patients with abdominal obesity with rimonabant reduces body weight and waist circumference but not atherosclerosis progression. Dr. Steve Nissen presented the results of the STRADIVARIUS study at the ACC-08 Annual Scientific Sessions in Chicago today.

This study evaluated the effect of rimonabant on progression of atherosclerosis in patients with abdominal obesity and coronary artery disease.

Patients with abdominal obesity have metabolic abnormalities which increases the risk of coronary artery disease. Rimonabant is a cannabinoid receptor (CB1) antagonist that enhances weight loss and improves obesity-related metabolic abnormalities. The investigators of the STRADIVARIUS trial explored the impact of rimonabant on coronary atherosclerosis progression as measured by intravascular ultrasound (IVUS).

Patients who had a waist circumference > 102 cm for men or > 88 cm for women and who were undergoing angiography took part in the study. The inclusion criteria also required two additional risk factors for the metabolic syndrome or current smoking.

A total of 839 patients who were randomized to placebo (n=417) or rimonabant 20 mg (n=422) underwent IVUS examination to assess atheroma volume [percent atheroma volume (PAV) and total atheroma volume (TAV)]. After 18 months, repeat IVUS was performed in the 676 patients who remained in the trial, regardless of whether they were still taking study drug or not.

Rimonabant compared with placebo was associated with a significant reduction in body weight (-4.3kg vs. -0.5kg, <0.001), glycosylated hemoglobin levels (-0.13% vs. 0.42%, p<0.001) and triglyceride levels (-20.5% vs. -6.2%, p<0.001) with an increase in HDL cholesterol levels (22.4% vs. 6.9%, p=0.001). The primary endpoint of % atheroma volume was not significantly different between the two groups (0.25% vs. 0.51%, p=0.22), however the total atheroma volume was reduced with rimonabant (-2.2% vs. 0.88%, p=0.003).

The composite of death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for revascularization, unstable angina and transient ischemic attacks were not different between the groups (10.4% vs. 11%).

Rimonabant was however was associated increased gastrointestinal (GI) side effects (33.6% vs. 17.8%, p<0.001) such as nausea (14.9% vs. 5.5%, p<0.001), diarrhea (7.8% vs. 3.4%, p=0.005), vomiting (5.5% vs. 1.9%, p=0.01) and erectile dysfunction (3.3% vs. 0.7%, p=0.04) and fatigue (10.9% vs. 6%, p=0.01). In addition, psychiatric disorders were more prevalent in the rimonabant group (43.4% vs. 28.4%, p<0.001).

The investigators concluded that rimonabant reduces body weight at the risk of increased GI and psychiatric adverse effects without significant impact on the progression of coronary artery atherosclerosis.

Source
Late Breaking Clinical Trials Session: ACC 08, April 1, 2008 Chicago