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CLINICAL STUDIES

Prevalence of valvular-regurgitation associated with dexfenfluramine three to five months after discontinuation of treatment

Neil J. Weissman, MD, FACC^*, John F. Tighe, Jr., MD, FACC^*, John S. Gottdiener, MD, FACC^* and John T. Gwynne, MD

^* Division of Cardiology, Georgetown University Medical Center, Washington, DC, USA
Department of Clinical Research, Wyeth-Ayerst Research, Philadelphia, Pennsylvania, USA

Manuscript received February 19, 1999; revised manuscript received June 24, 1999, accepted August 27, 1999.

Reprint requests and correspondence: Neil J. Weissman, Cardiovascular Research Foundation, Suite 4B-1, 110 Irving Street, NW, Washington, DC 20010
njw1{at}mhg.edu

OBJECTIVES

The goal of this study was to determine the prevalence of valvular regurgitation and abnormal valve morphology in patients three to five months after discontinuation of dexfenfluramine (Dexfen) therapy.

BACKGROUND

We previously reported the results of a randomized, double-blind, placebo-controlled trial of valvular structure and function in 1,073 patients treated either with Dexfen, with an investigational sustained-release dexfenfluramine (Dexfen SR), or with a placebo, with echocardiograms performed approximately one month from the last dose. Using FDA criteria (aortic regurgitation [AR] mild and/or mitral regurgitation [MR] moderate) we found no statistical difference among the groups, but when all degrees of valvular regurgitation were considered and when the two Dexfen groups were combined, there was a higher prevalence of any degree of AR, any degree of MR, and restricted posterior mitral leaflet mobility. However, it was unknown whether these differences in prevalence persisted.

METHODS

The double blind was maintained, and all patients were invited to return for a follow-up echocardiogram. Echocardiograms were acquired using a standardized protocol and assessed blindly to determine the degree of valvular regurgitation and valve leaflet thickness and mobility. We had an 80% power to detect a statistically significant change in paired proportions using the McNemar test (alpha = 0.05).

RESULTS

Echocardiograms were obtained on 941 patients with a median of 137 days after drug discontinuation. Aortic regurgitation (of any degree) was present in 13.8% of Dexfen (p = 0.41 compared to placebo), 10.7% of Dexfen SR (p = 0.64 compared to placebo), and 11.9% of placebo patients. The minor differences between patients treated with active drug versus placebo, which were found in the previous study, were no longer significant even when the groups were combined (p = 0.83 compared to placebo). Mitral regurgitation (of any degree) was present in 71.5% (p = 0.15 compared to placebo), 69.8% (p = 0.30 compared to placebo), and 70.5%, respectively. This was also not significantly different from placebo when both Dexfen groups were combined (p = 0.16). There was no difference in the prevalence of restricted posterior mitral leaflet mobility among the three groups (p = 0.19).

CONCLUSIONS

The small increase in prevalence of minor degrees of AR and MR in patients treated with two to three months of Dexfen previously reported is no longer present three to five months after discontinuation of medication. These data suggest that the degree of regurgitation observed in patients who used Dexfen for a relatively short duration does not progress over time.

Abbreviations and Acronyms   AR = aortic regurgitation   BID = twice a day   Dexfen = dexfenfluramine   Dexfen SR = sustained-release formulation of dexfenfluramine never marketed   kg/m2 = kilogram per square meter   LVOT = left ventricular outflow tract   MR = mitral regurgitation   phen-fen = phentermine/fenfluramine

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