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.


METHODS
Randomized, double-blind, placebo-controlled, multicenter study.


METHODS
Outpatient obesity centers.


METHODS
Obese persons 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.


METHODS
Pairs 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.
Weissman
N J
NJ
Cardiovascular Research Institute, Washington Hospital Center, 110 Irving Street NW, Suite 4B-1, Washington, DC 20010, USA.
Panza
J A
JA
Tighe
J F
JF
Gwynne
J T
JT
D000328:Adult; D000704:Analysis of Variance; D001022:Aortic Valve Insufficiency / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001067:Appetite Depressants / Q000009:adverse effects*; D020372:Dexfenfluramine / Q000009:adverse effects*; D018450:Disease Progression; D004311:Double-Blind Method; D015150:Echocardiography, Doppler; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008944:Mitral Valve Insufficiency / Q000000981:diagnostic imaging / Q000503:physiopathology*; D009765:Obesity / Q000188:drug therapy*; D010919:Placebos; D017366:Serotonin Receptor Agonists / Q000009:adverse effects*; D018709:Statistics, Nonparametric
D001067:Appetite Depressants; D010919:Placebos; D017366:Serotonin Receptor Agonists; D020372:Dexfenfluramine