Rimonabant does not lower percent atheroma volume

STRADAVARIUS trial demonstrated favorable results for rimonabant in the secondary endpoint of total atheroma volume.

CHICAGO — The cannabinoid receptor antagonist rimonabant failed to meet its primary efficacy endpoint, according to recently published study results presented at the 57th Annual Scientific Sessions of the American College of Cardiology.

While rimonabant succeeded in lowering total atheroma volume in patients with abdominal adiposity, it failed to meet its primary endpoint of decreased percent atheroma volume, said Steven E. Nissen, MD, chairman of the department of cardiovascular medicine at the Cleveland Clinic. He presented the results of the Strategy to Reduce Atherosclerosis Development Involving Administration of Rimonabant (STRADAVARIUS) trial. The results were also published in this week’s issue of JAMA.

“Treatment of abdominally obese coronary disease patients for 18 months with rimonabant reduced body weight 4.3 kg and waist circumference 4.5 centimeters, increased HDL by 22%, reduced triglycerides by 20%, high sensitivity C-reactive protein by 50%, and favorably affected HbA1c,” Nissen said. “Psychiatric and gastrointestinal adverse effects were more common with rimonabant, which resulted in a higher rate of drug discontinuation.”

Primary endpoint missed, secondary met

The researchers enrolled 839 patients with abdominal obesity into the randomized, placebo controlled trial. They performed intravascular ultrasound evaluation at baseline and again at follow-up in 676 patients who completed the trial. Patients were given either placebo (n=417) or 20 mg of rimonabant (n=422).

Percent atheroma volume increased at a lower, albeit statistically insignificant, rate in the rimonabant group (0.25%; 95% CI, –0.04 to 0.54), compared with the placebo group (0.51%; 95% CI, 0.22 to 0.80). The secondary efficacy endpoint of total atheroma volume, however, showed a decrease in the rimonabant group and an increase in the placebo group (P=.03).

“Development of effective and durable treatment strategies for management of obesity has proven a daunting challenge, and new approaches are greatly needed to reduce the burdens of this global epidemic and its metabolic consequences,” Nissen said. “We believe that CB1 inhibition shows promise for treatment of obesity-related atherosclerotic disease, but its benefits will need to be confirmed in additional trials, which are currently underway.” – by Eric Raible

For more information:

Nissen S. Effect of rimonabant on progression of atherosclerosis in patients with abdominal obesity and coronary artery disease. Session 412. Presented at: 57th Annual Scientific Session of the American College of Cardiology; March 29-April 1, 2008; Chicago.

Nissen S, Nicholls S, Wolski K, et al. Effect of rimonabant on progression of atherosclerosis on patients with abdominal obesity and coronary artery disease. JAMA. 2008;299:1547-1560.