Natural history of valvular regurgitation 1 year after discontinuation of dexfenfluramine therapy - A randomized, double-blind, placebo-controlled trial

Background: Previous studies have reported small increases in the prevalence of low-grade aortic and mitral regurgitation in patients treated with dexfenfluramine compared with placebo. However, whether valvular abnormalities develop or progress 1 year after discontinuation of dexfenfluramine therapy has not been determined. Objective: To assess change in valvular regurgitation and morphologic characteristics 1 year after discontinuation of dexfenfluramine therapy. Design: Randomized, double-blind, placebo-controlled, multicenter study. Setting: outpatient obesity centers. Patients: obese perrons who had been treated for 2 to 3 months with dexfenfluramine. sustained-release dexfenfluramine, or placebo. Blinding was maintained, and patients returned for repeated echocardiography at 1 year. Measurements: Pain of echocardiograms were evaluated with a side-by-side reading method for change in grade of valvular regurgitation, structure, and function. A standardized acquisition and reading protocol was followed, and a core laboratory was used. Results: 914 patients who had initial echocardiography returned for repeated echocardiography 11.4 +/- 1.0 months (mean +/- SD) after discontinuing study medication (10.0 +/- 1.0 months after initial echocardiography). Compared with the placebo group, a greater proportion of patients in both dexfenfluramine groups had decreased aortic regurgitation (P = 0.003 for the dexfenfluramine group, P = 0.02 for the sustained-release group). No change in mitral regurgitation or any other measure of valvular structure or function was seen in any treatment group. Conclusions: After dexfenfluramine therapy is taken for 2 to 3 months and discontinued, development or progression of any valvular regurgitation over the following year is unlikely. Echocardiographic evidence suggests that aortic regurgitation regresses in some previously treated patients.