American Heart Association Scientific Sessions: Rimonabant for Long-Term Weight Loss Management
Speaker: F. Xavier Pi-Sunyer, MD, MPH, Professor of Medicine, Columbia University College of Physicians and Surgeons, and Chief, Division of Endocrinology, Diabetes and Nutrition, Obesity Research Center, St. Luke’s-Roosevelt Hospital, New York, New York
Data from the second year of a two-year phase 3 study have confirmed the long-term benefits of rimonabant (Acomplia™, Sanofi-Aventis), the first of a new class of therapeutic agents called selective CB1 blockers, with respect to weight loss and reduction of associated cardiovascular risk factors.
The Rimonabant In Obesity-North America (RIO-NA) trial was a multinational, multicenter randomized, double-blind, placebo-controlled study designed to assess the effect of this agent on weight reduction, weight maintenance, and prevention of regained weight in overweight to obese patients with or without comorbidities. The study included 3,040 patients at 72 centers in the U.S. and Canada. Viagra Online Canadian Pharmacy
After a screening period of one week, patients were prescribed a mild hypocaloric diet designed to reduce daily caloric intake by 600 kilocalories (kcal). The patients were enrolled into a four-week, single-blind run-in period. Afterward, they were randomly assigned to receive placebo, rimonabant 5 mg, or rimonabant 20 mg for 52 weeks. A randomization ratio of 1:2:2 was used.
After one year of treatment, patients taking rimonabant were given either the same dose of rimonabant or placebo for a second year. A randomization ratio of 1:1 was used.
At one year, the reduction in waist circumference was 8.2 cm with rimonabant 20 mg, 4.7 cm with 5 mg, and 3.9 cm with placebo.
At two years, waist circumference was reduced by 8 cm for the rimonabant 20-mg group of patients, by 5 cm for the 5-mg group, and by 3.8 cm for the placebo group.
A total of 62.5% of patients who took rimonabant 20 mg for two years lost more than 5% of their initial body weight; 36.7% of those taking rimonabant 5 mg lost this amount; and 33.2% of the placebo group lost this amount.
During the same period, 32.8% of patients treated with rimonabant 20 mg lost more than 10% of their initial body weight; these numbers compared with 20% of subjects taking 5 mg and 16.4% taking placebo.
Throughout two years, metabolic parameters were also significantly improved in patients receiving rimonabant 20 mg. Levels of HDL-C increased by 24.5% in the high-dose rimonabant group, by 15.6% in the rimonabant 5-mg group, and by 13.8% in the placebo group. Triglyceride levels declined by 9.9% with rimonabant 20 mg, by 5.9% with rimonabant 5 mg, and by 1.6% with placebo.
Although diabetic patients were not included in the study, patients taking rimonabant 20 mg experienced significantly improved insulin sensitivity compared with those taking either the 5-mg dose or placebo.
Of particular note was the positive effect of rimonabant in patients with the metabolic syndrome. At baseline, 34.8% of patients who took rimonabant 20 mg met the criteria for metabolic syndrome. At the end of two years of treatment, this figure was reduced to 22.5%.
Atorvastatin Delays Progression of Alzheimer’s Disease
Speaker: D. Larry Sparks, PhD, Senior Scientist and Head, Roberts Laboratory for Neurodegenerative Disease Research, Sun Health Research Institute, Sun City, Arizona
The cholesterol-lowering (Pfizer) slowed cognitive decline and improved depressive symptoms in patients with mild-to-moderate Alzheimer’s disease (AD) and was safe and well tolerated over a one-year period.
Because both animal and human studies have shown that elevated cholesterol is an important risk factor for AD, a double-blind, placebo-controlled pilot study was designed to assess whether lowering cholesterol with atorvastatin could stabilize or improve cognition in people with mild-to-moderate AD. This proof-of-concept trial, entitled The Alzheimer’s Disease Cholesterol-Lowering Treatment Trial (ADCLT), enrolled 87 patients with a diagnosis of probable or possible AD of mild-to-moderate severity.
The patients were randomly assigned to receive either canadian atorvastatin 80 mg/day or placebo for one year. Sixty-three patients were considered evaluable at three months, and 46 individuals completed the 12-month study.
Patients taking cholinesterase inhibitors for AD were required to be on a stable dose for at least three months at study entry. The patients were evaluated at baseline, no more than 14 days after screening, and at three-, six-, nine-, and 12-month visits for assessment of cognition, overall mental function, and depression.
The Mini-Mental State Examination (MMSE), the cognitive portion of the Alzheimer’s Disease Assessment Scale (ADAS-Cog), and the Alzheimer’s Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) were administered at baseline and quarterly. Semiannually, the Neuropsychiatric Inventory and the ADCS-ADL were administered to assess behavior and activities of daily living. The Geriatric Depression Scale was administered at baseline and at the first visit.
Blood chemistries were evaluated quarterly for levels of cholesterol, the protein ceruloplasmin, the gene apolipoprotein E, and the antioxidant superoxide dismutase (DMSO).
At the start of the study, average ADAS-Cog scores for both groups was 20. Performance on the ADAS-Cog in the atorva-statin group was approximately three to five points higher than in the placebo group at six months and 12 months. The differences were significant at six months and approached significance at 12 months.
A trend toward a difference in ADCS-CGIC scores was achieved at nine months and 12 months in favor of atorvastatin versus placebo. Improvement on the Geriatric Depression Scale in the atorvastatin group and deterioration in the placebo group represented a significant benefit for atorvastatin.
Overall, 53% of the atorvastatin patients showed improvement or stabilization of AD in contrast to only 28% of those in the placebo group. After one year, patients taking atorvastatin exhibited significant improvement in their symptoms of depression. viagra soft
Atorvastatin also decreased low-density lipoprotein-cholesterol (LDL-C) levels by more than 50% (from 124 to 57 mg/dl). Total cholesterol fell by more than 40% (from 210 to 130 mg/dl).
Levels of DMSO were unaffected in both groups. Cerulo-plasmin concentrations were reduced in the statin group by about 10% to 15% compared with placebo.
A Key Marker, Lp-PLA2, for Predicting Coronary Artery Disease
Speaker: Wolfgang Koenig, MD, Professor, Department of Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, Germany
Elevated levels of the enzyme lipoprotein-associated phos-pholipase A2 (Lp-PLA2) (PLAC™ test, diaDexus) independently predict stable coronary artery disease (CAD), potentially offering an important therapeutic target to treat this disease.
To examine the association between Lp-PLA2 concentrations in plasma and risk of CAD, investigators measured Lp-PLA2 levels using the enzyme-linked immunosorbent assay (ELISA) in 312 patients with CAD and in 479 age-matched and sex-matched blood donor controls. Various lipid and lipo-protein parameters, as well as inflammatory and hemostatic parameters, were obtained to assess the relationship between Lp-PLA2 and sensitive inflammatory and hemostatic markers and a complete lipoprotein profile.
The results from this study support a growing body of evidence that Lp-PLA2 is a novel, independent risk marker for CAD. Lp-PLA2 concentrations were significantly higher in patients with CAD (296.1 ng/ml) than in controls (266 ng/ml) (P < .0001), and they were positively correlated with total cholesterol, LDL-C, and apoprotein B.
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In a multivariate analysis, the age-adjusted and sex-adjusted hazard ratio (HR) for the presence of CAD in the patient group with the highest levels of Lp-PLA2 was a statistically significant near-doubling of 1.61, the amount for patients in the bottom level.
Adjusting for traditional cardiovascular risk factors and statin use resulted in a hazard ratio (HR) of 2.04. After the researchers further controlled for other inflammatory and hemostatic parameters, such as C-reactive protein, among others, the HR was slightly attenuated to 1.84 but was still statistically significant.
On the basis of these results, as well as several other large case-control studies, the Food and Drug Administration cleared the test for Lp-PLA2 for use in the U.S. The test is indicated for the quantitative determination of Lp-PLA2 to aid in predicting an individual’s risk for a coronary event, in conjunction with clinical evaluation and patient risk assessment.