Natural History of Valvular Regurgitation 1 Year after Discontinuation of Dexfenfluramine Therapy

A Randomized, Double-Blind, Placebo-Controlled Trial

20 February 2001 | Volume 134 Issue 4 | Pages 267-273

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 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.

Measurements: 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.

Author and Article Information

From Washington Hospital Center, Washington, D.C.; National Heart, Lung, and Blood Institute, Bethesda, Maryland; and Wyeth-Ayerst Research, Philadelphia, Pennsylvania.

Disclaimer:Dr. Panza's work in this study, including the preparation of the manuscript, was completed in his private capacity. The views expressed in this article do not necessarily represent those of the National Institutes of Health, the Department of Health and Human Services, or the United States.

Acknowledgments:The authors thank Susan Perras, MSN, Maria Mattern, RN, and Jan Kitzen, PhD, for coordination of the clinical trial, assistance with the literature review, and technical preparation of the manuscript; John Vance, MD, for thoughtful review of the manuscript; Harvey Kushner, PhD, for assistance in developing the statistical analysis plan and providing statistical support during the data analysis and manuscript preparation; and Jonathan Tall, CNMT, CCRC, and Kenneth Horton, RDCS, for coordination of the central echocardiography laboratory.

Grant Support:By a research grant from the Wyeth-Ayerst Research Division of Wyeth Laboratories, Philadelphia, Pennsylvania. Dexfenfluramine hydrochloride capsules (Redux) were manufactured and distributed by Wyeth Laboratories, Inc., a Wyeth-Ayerst Company, under license from Interneuron Pharmaceuticals, Inc., Lexington, Massachusetts.

Requests for Single Reprints:Neil J. Weissman, MD, Cardiovascular Research Institute, Washington Hospital Center, 110 Irving Street NW, Suite 4B-1, Washington, DC 20010.

Current Author Addresses:Dr. Weissman: Cardiovascular Research Institute, Washington Hospital Center, 110 Irving Street NW, Suite 4B-1, Washington, DC 20010.

Dr. Panza: Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10, Room 7B-15, Bethesda, MD 20892.

Dr. Tighe: Cardiology Consultants of Westchester, 3078 Route 9W South, Suite 100, New Windsor, NY 12553.

Dr. Gwynne: Department of Clinical Research, Wyeth-Ayerst Research, Wyeth-Ayerst, 145 King of Prussia Road, Radnor, PA 19087.

Author Contributions:Conception and design: N.J. Weissman, J.A. Panza, J.F. Tighe, J.T. Gwynne.

Analysis and interpretation of the data: N.J. Weissman, J.A. Panza, J.F. Tighe, J.T. Gwynne.

Drafting of the article: N.J. Weissman, J.A. Panza, J.F. Tighe, J.T. Gwynne.

Critical revision of the article for important intellectual content: N.J. Weissman, J.A. Panza, J.F. Tighe, J.T. Gwynne.

Final approval of the article: N.J. Weissman, J.A. Panza, J.F. Tighe, J.T. Gwynne.

Provision of study materials or patients: N.J. Weissman.

Statistical expertise: N.J. Weissman.

Obtaining of funding: N.J. Weissman, J.T. Gwynne.

Administrative, technical, or logistic support: N.J. Weissman, J.T. Gwynne.

Collection and assembly of data: N.J. Weissman, J.A. Panza, J.F. Tighe, J.T. Gwynne.