Jacob Bell
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By: Susan Aldridge, medical journalist, PhD
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Summary
The slimming drug rimonabant aims to improve heart health through reducing abdominal obesity. In a large clinical trial, weight loss was noted, but the drug could not slow down the progression of coronary artery disease (CAD).
Introduction
With two thirds of the United States population now classed as overweight and one third as obese, there is urgent need to tackle this public health problem. For obesity, as is now well known, increases the risk of heart disease and other health problems. One aspect in particular, abdominal obesity, tends to cluster with other risk factors such as high blood pressure and raised cholesterol. This cluster is known as metabolic syndrome, and there is increasing interest in drugs that may target it. One such is rimonabant, the first of a new class called a selective cannabinoid type 1 receptor antagonist which can reduce abdominal obesity. These receptors are present throughout the nervous system and blocking them results in reduced food intake and weight loss. Rimonabant is now available as a weight loss aid in several countries but not, as yet, in the United States. The Food and Drug Administration (FDA) has expressed some reservations over the psychiatric side effects of the new drug. A team of researchers at the Cleveland Clinic, and elsewhere, has put rimonabant through its paces in the STRADIVARIUS Study (that stands for the Strategy to Reduce Atherosclerosis Development Involving Administration of Rimonabant). The goal was to see whether rimonabant can help patients at risk of heart disease by targeting abdominal obesity.
What was done
The STRADIVARIUS trial involved 112 centers in North America, Europe and Australia. Subjects were eligible for inclusion if they required a coronary angiography exam to investigate for heart disease. They also had a waist circumference of greater than 34.6 inches for women, and greater than 40.2 inches for men. The participants also had two or more of the classic metabolic syndrome risk factors like raised triglycerides or blood pressure. Another eligibility criterion was being a current smoker. In other words, these individuals had a higher than usual risk of CAD.
The thickening of the arteries with a deposit called atheroma, which sets the scene for CAD, was measured using a technique called intravascular ultrasound (IVUS). Thus, the impact of rimonabant on atheroma was measured, along with metabolic syndrome factors. Measurements were taken at the start and at regular intervals during the 20 month trial during which time the 839 participants received either 20 mg a day of rimonabant or placebo.
What was found
Rimonabant fulfils its promise in reducing weight, especially abdominal obesity. The participants on the drug had a larger reduction in body weight - an average of nearly 10 pounds - than the placebo group and also reduced their waist circumference by nearly two inches. There were also increases in high density lipoprotein cholesterol (HDL, or 'good' cholesterol) and decreases in triglycerides. But low density lipoprotein cholesterol (LDL, or 'bad' cholesterol) and blood pressure changes were not different between the two groups. The IVUS measurements did not show a significant change over the trial, which suggests that rimonabant does not slow the progression of heart disease. Moreover, there was a high incidence of psychiatric side effects, albeit mainly mild in nature, in the rimonabant group - which is precisely why the FDA is not ready to approve it yet.
What this study means
The researchers point out that the STRADIVARIUS trial has failed to meet its primary endpoint, which was to show that rimonabant could reduce the progression of atheroma as shown by IVUS measurements. Therefore, further research is needed to determine the role of this drug in the treatment of abdominal obesity in patients with metabolic syndrome and risk factors for CAD.
Source
Effect of rimonabant of progression of atherosclerosis in patients with abdominal obesity and coronary artery disease
SE. Nissen, SJ. Nicholls, JAMA Express, April 1, 2008, vol. 299, pp. 1547--1560
Source: Rimonabant Doesn't Reduce Heart Risk
Tools:
Print this page
Bookmark this page
Forward this page to a friend
Summary
The slimming drug rimonabant aims to improve heart health through reducing abdominal obesity. In a large clinical trial, weight loss was noted, but the drug could not slow down the progression of coronary artery disease (CAD).
Introduction
With two thirds of the United States population now classed as overweight and one third as obese, there is urgent need to tackle this public health problem. For obesity, as is now well known, increases the risk of heart disease and other health problems. One aspect in particular, abdominal obesity, tends to cluster with other risk factors such as high blood pressure and raised cholesterol. This cluster is known as metabolic syndrome, and there is increasing interest in drugs that may target it. One such is rimonabant, the first of a new class called a selective cannabinoid type 1 receptor antagonist which can reduce abdominal obesity. These receptors are present throughout the nervous system and blocking them results in reduced food intake and weight loss. Rimonabant is now available as a weight loss aid in several countries but not, as yet, in the United States. The Food and Drug Administration (FDA) has expressed some reservations over the psychiatric side effects of the new drug. A team of researchers at the Cleveland Clinic, and elsewhere, has put rimonabant through its paces in the STRADIVARIUS Study (that stands for the Strategy to Reduce Atherosclerosis Development Involving Administration of Rimonabant). The goal was to see whether rimonabant can help patients at risk of heart disease by targeting abdominal obesity.
What was done
The STRADIVARIUS trial involved 112 centers in North America, Europe and Australia. Subjects were eligible for inclusion if they required a coronary angiography exam to investigate for heart disease. They also had a waist circumference of greater than 34.6 inches for women, and greater than 40.2 inches for men. The participants also had two or more of the classic metabolic syndrome risk factors like raised triglycerides or blood pressure. Another eligibility criterion was being a current smoker. In other words, these individuals had a higher than usual risk of CAD.
The thickening of the arteries with a deposit called atheroma, which sets the scene for CAD, was measured using a technique called intravascular ultrasound (IVUS). Thus, the impact of rimonabant on atheroma was measured, along with metabolic syndrome factors. Measurements were taken at the start and at regular intervals during the 20 month trial during which time the 839 participants received either 20 mg a day of rimonabant or placebo.
What was found
Rimonabant fulfils its promise in reducing weight, especially abdominal obesity. The participants on the drug had a larger reduction in body weight - an average of nearly 10 pounds - than the placebo group and also reduced their waist circumference by nearly two inches. There were also increases in high density lipoprotein cholesterol (HDL, or 'good' cholesterol) and decreases in triglycerides. But low density lipoprotein cholesterol (LDL, or 'bad' cholesterol) and blood pressure changes were not different between the two groups. The IVUS measurements did not show a significant change over the trial, which suggests that rimonabant does not slow the progression of heart disease. Moreover, there was a high incidence of psychiatric side effects, albeit mainly mild in nature, in the rimonabant group - which is precisely why the FDA is not ready to approve it yet.
What this study means
The researchers point out that the STRADIVARIUS trial has failed to meet its primary endpoint, which was to show that rimonabant could reduce the progression of atheroma as shown by IVUS measurements. Therefore, further research is needed to determine the role of this drug in the treatment of abdominal obesity in patients with metabolic syndrome and risk factors for CAD.
Source
Effect of rimonabant of progression of atherosclerosis in patients with abdominal obesity and coronary artery disease
SE. Nissen, SJ. Nicholls, JAMA Express, April 1, 2008, vol. 299, pp. 1547--1560
Source: Rimonabant Doesn't Reduce Heart Risk
