Based on the STRADAVARIUS results, Rimonabant may slow the progression of coronary disease in abdominally obese patients, but not decrease it significantly, according to a presentation by Steve Nissen, MD, at the 2008 American College of Cardiology (ACC) Scientific Sessions in Chicago.
Sanofi-Aventis’ Rimonabant is an experimental weight-loss agent not yet approved in the U.S., but is available in some European countries, and represents the first of a new class of drugs that work by inhibiting cannabanoid type 1 (CB1) receptors.
Nissen, lead investigator and chair of the cardiovascular-medicine department at the Cleveland Clinic in Ohio, pointed out that “34 percent of people in the U.S. population have a body mass index greater than 30.”
The STRADIVARIUS (Strategy to Reduce Atherosclerosis Development Involving Administration of Rimonabant - The Intravascular Ultrasound Study) Trial, which appeared in the April 2 issue of the Journal of American Medical Association, randomized 839 patients at 112 centers in North America, Europe and Australia to receive either Rimonabant or placebo, and measured progression of disease by intravascular ultrasound, a technique that directly measures plaque buildup in the coronary arteries.
The investigators found that patients treated with Rimonabant lost about 9.5 pounds and 1.8 inches in waist circumference; their HDL cholesterol rose 22.4 percent, triglycerides decreased 20 percent and CRP levels decreased 50 percent.
Nissen reported that the primary endpoint, the percent atheroma volume (PAV) did not show a statistically significant effect on IVUS, and therefore, failed to meet its primary endpoint. However, the secondary endpoint, the total atheroma volume (TAV) did show a statistically significant effect.
Yet, the researchers noted that the positive results for the secondary endpoint suggest that this approach has the potential to reduce plaque buildup in the coronaries, which will need to be confirmed in further trials.
Nissen conceded that development of effective and durable treatment strategies for obesity managing has proven a daunting challenge. He said that “new approaches are greatly needed to reduce the burdens of this global epidemic and its metabolic consequences.”
“We believe CB1inhibition shows promise for treatment of obesity-related atherosclerotic disease, but its benefits will need to be confirmed in additional trials, which are currently underway,” Nissen said.