Rimonabant can lower heart disease risk factors

NEW YORK (Reuters Health) – Rimonabant, know by the trade
name Acomplia, results in weight loss and improves the risk
profile in obese patients with high cholesterol who are at
increased risk of cardiovascular disease, new study findings
show.

Reuters Health has previously reported that rimonabant is
effective in reducing weight. The current study, supported by
Sanofi-Aventis and published in The New England Journal of
Medicine, included overweight or obese patients at high risk
for cardiovascular disease.

Dr. Jean-Pierre Despres, from Laval University in Ste.-Foy,
Quebec, Canada, and his associates randomly assigned 340
subjects to rimonabant 5 mg, 344 to rimonabant 20 mg, and 334
to placebo. All of the patients were instructed to maintain a
low-calorie diet.

At the end of 12 months, those in the placebo group lost an
average of 2.3 kilograms (kg), compared with a weight loss of
4.2 kg in the lower-dose rimonabant group and 8.6 kg in the
higher-dose rimonabant group. Weight loss occurred during the
first months and then stabilized without regain throughout the
rest of the study period. Reductions in waist circumference
followed a similar pattern.

Triglycerides fell by 15.8 percent among those taking the
higher dose of rimonabant, while remaining steady in the other
two groups. HDL cholesterol, the “good” cholesterol, increased
by 12.2 percent in the placebo group, 15.6 percent in the
lower-dose rimonabant group and 23.4 percent in the higher-dose
rimonabant group.

The prevalence of the metabolic syndrome fell to 41.0
percent, 40.0 percent and 25.8 percent, respectively, from an
overall prevalence of 54 percent at the start of the study. The
metabolic syndrome is a cluster of conditions such as high
blood pressure and high blood sugar levels that raise the risk
of heart disease and diabetes.

The higher dose of rimonabant also resulted in lower blood
sugar levels and lower C-reactive protein levels, high levels
of which are associated with diabetes and heart disease,
respectively. The drug also resulted in lower blood pressure
and higher levels of adiponectin.

“The weight-loss independent effect of rimonabant on
adiponectin levels…may be of clinical importance, since a
high adiponectin level has been reported to be predictive of a
reduced risk of diabetes and cardiovascular events,” the
authors point out.

They observed that, although the study drop-out rate was
similar in the three groups, more subjects in the 20-mg
rimonabant group discontinued treatment because of adverse
effects, primarily depression (2.9 percent), anxiety (1.7
percent), and nausea (1.2 percent).

“Although pharmacotherapy alone will not eradicate the
epidemic of obesity,” Despres and his team write, the current
findings provide evidence that rimonabant and other
cannabinoid-1-receptor blockers may represent a new way of
improving unfavorable cardiovascular risk factors in patients
with high cholesterol who are overweight or obese.

SOURCE: The New England Journal of Medicine, November 17,
2005.