An assessment of heart-valve abnormalities in obese patients taking dexfenfluramine, sustained-release dexfenfluramine, or placebo. Sustained-Release Dexfenfluramine Study Group.

Author: Weissman NJ, Tighe JF Jr, Gottdiener JS, Gwynne JT

Author affiliation: Division of Cardiology and the Cardiovascular Institute, Georgetown University Medical Center, Washington, DC 20007-2197, USA.

Publication date & source: 1998.09.10, N Engl J Med., 339(11):725-32.

Publication type: Clinical Trial; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

BACKGROUND: The appetite-suppressant drug fenfluramine, usually given in combination with phentermine, has been reported to be associated with cardiac valvular regurgitation. Concern has been raised that the d-enantiomer of fenfluramine, dexfenfluramine, may also cause this problem. We were able to study the question by modifying an ongoing trial comparing dexfenfluramine with regular dexfenfluramine and placebo. METHODS: We modified our randomized, double-blind, placebo-controlled study of dexfenfluramine to include echocardiographic examinations of 1072 overweight patients within a median of one month after the discontinuation of treatment. The patients (approximately 80 percent of whom were women) had been randomly assigned to receive dexfenfluramine (366 patients), investigational sustained-release dexfenfluramine (352 patients), or placebo (354 patients). The average duration of treatment was 71 to 72 days in each of the three groups. Echocardiograms were assessed in a blinded fashion. RESULTS: When all degrees of valvular regurgitation were considered and when the two dexfenfluramine groups were combined, there was a higher prevalence of any degree of aortic regurgitation (17.0 percent vs. 11.8 percent, P=0.03) and any degree of mitral regurgitation (61.4 percent vs. 54.4 percent, P=0.01) in the active-treatment groups than in the placebo group. These differences were primarily due to a higher prevalence of physiologic, trace, or mild regurgitation. Analyses that used the criteria of the Food and Drug Administration for aortic regurgitation of mild or greater severity and mitral regurgitation of moderate or greater severity found no statistically significant difference among the groups (P=0.14 to 0.75). These analyses showed that aortic regurgitation of mild or greater severity occurred in 5.0 percent of the patients in the dexfenfluramine group, 5.8 percent of those in the sustained-release dexfenfluramine group, 5.4 percent of those in the two active-treatment groups combined, and 3.6 percent of those in the placebo group. Mitral regurgitation of moderate or greater severity occurred in 1.7, 1.8, 1.8, and 1.2 percent, respectively. Aortic regurgitation of mild or greater severity, mitral regurgitation of moderate or greater severity, or both occurred in 6.5 percent, 7.3 percent, 6.9 percent, and 4.5 percent, respectively. CONCLUSIONS: The increased prevalence of aortic and mitral regurgitation in patients treated with dexfenfluramine was small, and the degree of regurgitation was usually classified as physiologic, trace, or mild. However, the duration of therapy was short, and whether therapy of longer duration would yield the same or different results is not known.