Heart research focusing on obesity, atrial fib, diabetes

October 25, 2004

Obesity, atrial fibrillation/flutter, and diabetic nephropathy, which are clearly on the rise worldwide, were the key areas of attention at the European Society of Cardiology 2004 annual meeting, held in Munich, Germany, recently.

Obesity, atrial fibrillation/flutter, and diabetic nephropathy, which are clearly on the rise worldwide, were the key areas of attention at the European Society of Cardiology 2004 annual meeting, held in Munich, Germany, recently.

Now that Europe is clearly also experiencing a rapid rise in obesity, as is the case in the United States, there was great interest in RIO-EUROPE, a trial of rimonabant (Sanofi-Aventis), an agent that targets the endocannabinoid system (ECS) with the aim of positively affecting food intake. Rimonabant is the first in this new class of therapeutics called selective CB1blockers.

RIO-EUROPE is a two-year, large-scale (approximately 1,500 patients) placebo-controlled study of rimonabant 5 or 20 mg once daily. According to Luc Van Gaal, M.D., a professor of medicine at Antwerp University, Belgium, patients were asked to reduce their daily diet by 600 kcal/day). To be included, patients had a body mass index (BMI) Ž 30 kg/m2 or BMI > 27 with comorbidity. The primary endpoint was absolute change in weight from baseline at one year.

Discontinuations for serious adverse events were similar between groups: 8.3% for RMN 5 mg, 14.5% for RMN 20 mg, and 9.2% for placebo. Van Gaal concluded that treatment with RMN brought about significant reductions in weight, waist circumference/abdominal obesity, and lipid and glycemic profile with a good safety profile.

The clinical use of the oldest and perhaps most effective antiarrhythmic drug, amiodarone, is often limited by extra-cardiac side effects attributed to lipophilic qualities linked to iodine within the amiodarone molecule. Dronedarone, a derivative of amiodarone, was designed without iodine to avoid these side effects, according to professor Stefan H. Hohnloser, M.D., Goethe University, Frankfurt, Germany.

In matching trials, EURIDIS in Europe and ADONIS in North/ South America, Africa, and Australia, dronedarone was compared with placebo among 1,234 patients who had one or more episodes of atrial fibrillation (AF) or atrial flutter (AFL) in the prior three months. All were in sinus rhythm at randomization. In both trials, patients were randomized 2:1 (n = 828/409) to dronedarone 800 mg (400 mg b.i.d.) or placebo for one year. The primary endpoint was time from randomization to first documented AF/AFL recurrence.

Serious adverse event rates were similar, and there was no evidence of proarrhythmia, no cases of torsades de pointes, and no detection of dysthyroidism.

Hohnloser concluded that for AF/AFL recurrence, dronedarone was superior to placebo. He commented also, at a subsequent press event, "When you treat patients in clinical practice with amiodarone, there is no question that you will encounter some with organ toxicity within a year, and the severity and prevalence increase over time."