Background The appetite-suppressant drug fenfluramine, usuallygiven in combination with phentermine, has been reported tobe associated with cardiac valvular regurgitation. Concern hasbeen raised that the d-enantiomer of fenfluramine, dexfenfluramine,may also cause this problem. We were able to study the questionby modifying an ongoing trial comparing sustained-release dexfenfluraminewith regular dexfenfluramine and placebo.
Methods We modified our randomized, double-blind, placebo-controlledstudy of dexfenfluramine to include echocardiographic examinationsof 1072 overweight patients within a median of one month afterthe discontinuation of treatment. The patients (approximately80 percent of whom were women) had been randomly assigned toreceive dexfenfluramine (366 patients), investigational sustained-releasedexfenfluramine (352 patients), or placebo (354 patients). Theaverage duration of treatment was 71 to 72 days in each of thethree groups. Echocardiograms were assessed in a blinded fashion.
Results When all degrees of valvular regurgitation were consideredand when the two dexfenfluramine groups were combined, therewas a higher prevalence of any degree of aortic regurgitation(17.0 percent vs. 11.8 percent, P=0.03) and any degree of mitralregurgitation (61.4 percent vs. 54.4 percent, P=0.01) in theactive-treatment groups than in the placebo group. These differenceswere primarily due to a higher prevalence of physiologic, trace,or mild regurgitation. Analyses that used the criteria of theFood and Drug Administration for aortic regurgitation of mildor greater severity and mitral regurgitation of moderate orgreater severity found no significant difference among the groups(P=0.14 to 0.75). These analyses showed that aortic regurgitationof mild or greater severity occurred in 5.0 percent of the patientsin the dexfenfluramine group, 5.8 percent of those in the sustained-releasedexfenfluramine group, 5.4 percent of those in the two active-treatmentgroups combined, and 3.6 percent of those in the placebo group.Mitral regurgitation of moderate or greater severity occurredin 1.7, 1.8, 1.8, and 1.2 percent, respectively. Aortic regurgitationof mild or greater severity, mitral regurgitation of moderateor greater severity, or both occurred in 6.5 percent, 7.3 percent,6.9 percent, and 4.5 percent, respectively.
Conclusions We found a small increase in the prevalence of aorticand mitral regurgitation in patients treated with dexfenfluramine,and the degree of regurgitation was in most cases classifiedas physiologic, trace, or mild. However, the duration of therapywas short, and whether therapy of longer duration would yieldthe same or different results is not known.
Source Information
From the Division of Cardiology and the Cardiovascular Institute, Georgetown University Medical Center, Washington, D.C. (N.J.W., J.F.T., J.S.G.); and the Department of Clinical Research, Wyeth–Ayerst Research, Philadelphia (J.T.G.).
Address reprint requests to Dr. Weissman at the Division of Cardiology, Georgetown University Medical Center, 3800 Reservoir Rd., NW, Washington, DC 20007-2197.
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