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New class may help smokers quit, curb post-cessation weight gain

In phase 3 trials, the first agent in a novel class known as the selective cannabinoid type 1 receptor blockers doubled the odds of quitting smoking while reducing post-cessation weight gain compared with placebo. The agent, rimonabant, also improved several features of the metabolic syndrome in patients with abdominal obesity, reported researchers at the 53rd Annual Scientific Session of the American College of Cardiology (ACC).

Chronic nicotine use leads to overstimulation of the endocannabinoid system, which plays a critical role in regulation of food intake and energy expenditure. "Rimonabant might restore the balance in that disturbed endocannabinoid system," said Robert M. Anthenelli, MD, associate professor of psychiatry and neuroscience, University of Cincinnati, and lead investigator of one of the studies presented at ACC.

In one study, 787 people who smoked at least 2 packs of cigarettes per day and expressed a desire to quit but were previously unable to do so were randomized to once-daily doses of rimonabant, 5 mg; rimonabant, 20 mg; or placebo. Treatment was initiated 2 weeks prior to the attempt at smoking cessation and was continued for another 8 weeks.

The cessation rates were 27.6% among the patients assigned 20 mg of rimonabant and 16.1% among the placebo recipients (P=.004). The 5-mg dose of rimonabant had no effect on the cessation rate.

Overweight and obese patients lost weight on rimonabant during the 10 weeks of treatment while normal weight smokers did not. Overweight smokers assigned to rimonabant experienced a weight loss of 0.5 kg versus a weight gain of 0.9 kg in the placebo group. Obese patients randomized to rimonabant lost 0.6 kg versus a weight gain of 1.3 kg among obese patients randomized to placebo (P<.001).

In terms of adverse effects, nausea was more common with rimonabant compared to placebo (15.7% vs 9.2%), as was upper respiratory tract infection (10.0% vs 5.7%).

Rimonabant was also studied in 1,036 untreated dyslipidemic patients with central obesity and a BMI of 27­40 kg/m2. The patients were randomized to once-daily placebo or the 5- or 20-mg dose of rimonabant for 1 year. Patients randomized to 20 mg of rimonabant lost a mean of 20 lb and 3.4 inches in waist circumference from baseline, which was significantly greater compared to placebo (P<.001), said lead investigator Jean-Pierre Desprès, PhD, director of research, department of cardiology, Université Laval, Quebec City, Montreal.

The patients receiving 20 mg/d of rimonabant also demonstrated an improvement in their lipid profiles. These patients experienced a 23% increase in high-density lipoprotein (HDL) cholesterol and a 15% reduction in triglycerides from baseline. In addition, rimonabant 20 mg was associated with a favorable shift in low-density lipoprotein (LDL) particle size, from smaller atherogenic particles to larger, less atherogenic LDL particles. Because of these lipid changes, "we saw a 50% decrease in the number of patients who met the criteria for metabolic syndrome, from 52.9% to 25.8%," said Dr Desprès.

Because cannabinoid receptors are expressed in adipose tissue, adiponectin was measured in a subset of patients. "Adiponectin levels are markedly reduced in abdominally obese patients," Dr Desprès said. In the 20-mg rimonabant group, plasma adiponectin increased by 41% compared with an increase of only 13.6% in the placebo group (P<.001).

"This increase in adiponectin may explain the effect of the drug on cardiovascular risk factors," said Dr Desprès.

>Enoxaparin is an effective and safe alternative to unfractionated heparin (UFH) in the early and invasive management of high-risk patients with non-ST-elevation acute coronary syndromes (ACS), said Robert Califf, MD, at the 53rd Annual Scientific Session of the American College of Cardiology (ACC).

Mark McClellan, MD, PhD, now administrator of the Centers for Medicare and Medicaid Services (CMS), is seeking more evidence-based information about how medical treatments affect patients in the real world. Dr McClellan says his first priority is to use the new Medicare pharmacy program, starting with the drug discount card, to lower drug costs. One prime strategy for doing so is to evaluate which therapies are most efficacious as well as cost-effective for specific patient subgroups in order to curb unnecessary spending on prescription drugs.

Rasagiline (Teva/Eisai), a second-generation irreversible MAO inhibitor highly selective for type B of the enzyme, is expected to gain FDA approval in late 2004/early 2005 for the treatment of Parkinson’s disease in monotherapy or as adjunct therapy to levodopa. Rasagiline is more potent than selegiline, the only FDA-approved drug within the same class, and may be devoid of the undesirable effects (blood pressure increases, euphoria, and sleep disturbances) often reported with selegiline. Rasagiline has been studied and proven effective versus placebo in patients with moderate and advanced Parkinson’s disease in both phase 2 and 3 clinical trials. The drug is administered orally once daily and does not require titration. Furthermore, rasagiline has demonstrated neuroprotective activity in various in vitro models and may show promise in the treatment of other neurologic diseases; however, these properties have yet to be studied in humans.

Adenosine Tc99m-sestamibi stress myocardial perfusion scintigraphy can identify a low-risk population of patients with acute myocardial infarction (AMI) who can be discharged safely from the hospital without coronary angiography, said John J. Mahmarian, MD, at the 53rd Annual Scientific Session of the American College of Cardiology (ACC).

Erectile dysfunction (ED) is now recognized as a common problem in men. Several medical problems, including diabetes mellitus, coronary artery disease, hypertension, and hyperlipidemia are known to increase the likelihood of developing ED. Diagnosis depends on an adequate history and physical examination. Several therapies are now available for the treatment of ED. With the advent of the phosphodiesterase type 5 (PDE5) inhibitors, therapy for ED has become more acceptable for many men. Oral therapy is usually the first-line treatment due to the ease of use and the effectiveness of this therapy. For men who do not respond to or have a contraindication to PDE5 therapy, intrapenile injection therapy, intraurethral therapy, and vacuum devices are effective alternatives.