MEDICATIONS: DIET DRUG USE ASSOCIATED WITH INCREASED PREVALENCE OF HEART VALVE ABNORMALITIES

Users of Phen-Fen and Dexfenfluramine have higher rates of aortic regurgitation, but no increase in serious cardiac events

Users of the diet drugs dexfenfluramine and phentermine/fenfluramine had more than double the risk of having developed heart valve abnormalities, according to an article appearing in the April 5 issue of The Journal of the American Medical Association (JAMA). However, the researchers did not find an increased prevalence of serious cardiovascular or cardiac outcomes such as heart attack, congestive heart failure or ventricular arrhythmia.

Julius M. Gardin, M.D., from the University of California, Irvine, and colleagues evaluated the cardiovascular status and the prevalence of valvular abnormalities in 1,473 patients from 25 U.S. clinical centers who were treated for obesity with the anorexigens (appetite controlling diet drugs) dexfenfluramine or phentermine/fenfluramine. The authors evaluated the prevalence of valvular abnormalities and clinical signs and symptoms in large cohorts of dexfenfluramine and phentermine/fenfluramine treated patients compared with an untreated control group.

According to the American Medical Association's Encyclopedia of Medicine, aortic and mitral regurgitation indicates the backflow of blood within the heart because of heart valve insufficiency or incompetence. For example, in the case of aortic regurgitation, blood leaving the heart for the body through the aortic valve backwashes into the left ventricle. According to background information in the article, in 1997 reports of valvular abnormalities resulted in the voluntary withdrawal of dexfenfluramine and fenfluramine from the market.

"Prevalence rates and relative risk (RR) of aortic regurgitation were significantly increased in anorexigen-treated patients and were 8.9 percent in the dexfenfluramine group (RR 2.18 [or a risk of 2.18 times that of the control group]), 13.7 percent in the phentermine/fenfluramine group (RR 3.34 [or a risk of 3.34 times that of the control group]) and 4.1 percent in the untreated group," write the authors.

Moderate or severe aortic regurgitation was observed infrequently. The prevalence of mitral regurgitation was approximately the same between the treated and untreated groups. There was no statistical difference in the prevalence of serious cardiac events, including heart attack, congestive heart failure or ventricular arrhythmia, between the treated and untreated groups.

In an accompanying editorial, Hershel Jick, M.D., from the Boston University School of Medicine, Lexington, Mass., considers the Gardin et al study in the context of other researchers' dexfenfluramine and phentermine/fenfluramine study results. Dr. Jick cautions that the JAMA study may underestimate the actual prevalence of heart valve abnormalities related to the use of dexfenfluramine and phentermine/fenfluramine.

"Several factors apparent from the body of evidence linking fenfluramines and valve disorders appear to favor a casual connection," writes Dr. Jick. "The majority of echocardiographic studies comparing asymptomatic fenfluramine recipients with comparable nonrecipients show a substantially increased prevalence of valve disorders in the fenfluramine-treated patients. The most common abnormality is [aortic regurgitation], which is most often minor and benign (i.e., associated with no cardiac symptoms), and clinically important valvular disease attributable to fenfluramines appears to be uncommon."