MADRID — Rimonabant, the novel cannabinoid type 1 receptor-blocking drug that has been shown to induce weight loss, improve glucose metabolism, raise HDL cholesterol, and lower triglycerides, also appears to lead to small but meaningful reductions in blood pressure in hypertensive obese patients.
That finding comes from a new analysis of pooled data from the four major rimonabant trials involving over 6,600 patients. Among patients with elevated BP at baseline (greater than 143/89 mm Hg for nondiabetics, and greater than 130/85 mm Hg for diabetics), the use of 20 mg/day of rimonabant was associated with a mean systolic pressure reduction of 7.5 mm Hg and a mean diastolic reduction of 5.2 mm Hg. This compares favorably with the mean reductions of 4.7 mm Hg and 3.0 mm Hg, respectively, in patients who received placebo, Dr. Luc Van Gaal reported at the annual meeting of the European Society of Hypertension.
This is the first indication that the cannabinoid receptor blocker may have a role in blood pressure reduction, and it is clearly good news for the treatment of obese or overweight patients who have multiple cardiovascular risk factors.
But the drug should not be misconstrued as being an antihypertensive agent per se. The observed reduction in blood pressure “is mediated by weight loss only, with the drug having no direct effect on blood pressure at this dose level,” stressed Dr. Van Gaal, head of diabetology, metabolism and clinical nutrition at the University Hospital of Antwerp, Belgium.
Rimonabant, which is being developed by Sanofi-Aventis, is under review by the Food and Drug Administration.
The Rimonabant in Obesity and Related Metabolic Disorders (RIO) trial series comprises four distinct international multicenter trials looking at the effects of the drug in nonoverlapping populations.
RIO-North America involved 3,040 obese or overweight patients without comorbidities in the United States and Canada; RIO-Europe looked at a similar population of 1,507 European patients; RIO-Lipids involved 1,033 obese people with untreated dyslipidemia; RIO-Diabetes involved 1,045 obese or overweight patients with type 2 diabetes.
All four studies included hypertensive and nonhypertensive individuals. Across the RIO trials, the percentage of hypertensive subjects ranged from 13% in RIO-North America to 54% in RIO-Diabetes.
The reduction in blood pressure seen in the aggregate RIO population was most pronounced among those with dyslipidemia who were also hypertensive at baseline. In this cohort, the drug was associated with a mean 11.9-mm Hg reduction in systolic pressure and a mean 5.9-mm Hg reduction in diastolic pressure. In contrast, the placebo group had a 6.3-mm Hg drop in systolic and a 2.0-mm Hg drop in diastolic pressure.
In the RIO-Diabetes trial, rimonabant had little apparent effect on blood pressure in those who were normotensive at baseline. But those who were hypertensive at the outset had a 5.5-mm Hg decrease in systolic and a 4.4-mm Hg reduction in diastolic pressure. These differences were statistically significant, and given that nearly 60% of those who were hypertensive were already on antihypertensive medications, these incremental reductions are clinically meaningful, Dr. Van Gaal said.
A linear regression analysis plotting the blood pressure changes against changes in body weight showed nearly identical curves for rimonabant and placebo. The degree of pressure reduction with rimonabant is equivalent to that seen for placebo in patients matched for the same degree of weight loss.
That said, the observed reduction in blood pressure “adds to the other cardiometabolic benefits demonstrated for rimonabant, such as reduced body weight and waist circumference, improved lipid profile, and improved glycemic control,” Dr. Van Gaal said.
Dr. Nick Finer of the Addenbrooke's Hospital, National Health Service Trust, Cambridge, England, commented, “Currently, we use a wide variety of drugs to treat the cardiovascular, inflammatory, endocrine and adipose aspects of the disease of abdominal obesity. Cannabinoid 1 receptor blockade seems to affect all of these areas with one drug. In principle, this could be drug sparing. It is a very exciting development.”