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Appetite Suppressants and Valvular Regurgitation

A report last year of valvular regurgitation in 24 individuals taking the appetite suppressants fenfluramine and phentermine (see JWCard Oct 1997, p. 80, accession number 981009001, and N Engl J Med 337:581) contributed to the withdrawal of these drugs from the market. Now three controlled studies suggest that concern was warranted.

The first study compared echocardiographic findings in 233 obese individuals who had taken dexfenfluramine (the *d*-isomer of fenfluramine) alone, dexfenfluramine with phentermine, or fenfluramine with phentermine, with those of 233 controls matched for sex, age, and body-mass index. Cardiac valve disease was present in 22.7 percent of individuals who had received the drugs and 1.3 percent of controls. The odds ratio for cardiac-valve abnormalities in individuals who used these drugs was 22.6.

Another study compared the echocardiograms of patients randomized to dexfenfluramine (n=366), sustained-release dexfenfluramine (n=352), or placebo (n=354). Treatment duration averaged 70 days. Aortic regurgitation of any severity was significantly more common in the treatment groups than in the placebo group (17 percent vs. 12 percent). Mitral regurgitation of any severity was more common in the dexfenfluramine and sustained-release groups than in the placebo group (61 percent and 62 percent vs. 54 percent).

The third study used a database from the U.K. to identify 9,765 obese individuals who had taken dexfenfluramine, fenfluramine, or phentermine and 9,281 weight-matched controls. There were no cases of valvular abnormalities in the controls or among the individuals who took phentermine alone. The five-year cumulative incidence of valvular abnormalities per 10,000 subjects was 7.1 for individuals who took either dexfenfluramine or fenfluramine for less than four months and 35.0 for those who took the medications for four months or more.

Comment: These reports support the association between fenfluramine (and its *d*-isomer) and heart-valve regurgitation. An editorialist suggests that all patients who received these medications should be examined. Referral for echocardiography is recommended for those who have a murmur or other evidence of valvular heart disease or who received the drugs for three or more months or at high doses.

— HM Krumholz

Published in Journal Watch Cardiology December 31, 1998

Citation(s):

Khan MA et al. The prevalence of cardiac valvular insufficiency assessed by transthoracic echocardiography in obese patients treated with appetite-suppressant drugs. N Engl J Med 1998 Sep 10 339 713-718.

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Weissman NJ et al. An assessment of heart-valve abnormalities in obese patients taking dexfenfluramine, sustained-release dexfenfluramine, or placebo. N Engl J Med 1998 Sep 10 339 725-732.

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Jick H et al. A population-based study of appetite-suppressant drugs and the risk of cardiac-valve regurgitation. N Engl J Med 1998 Sep 10 339 719-724.

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Devereaux RB. Appetite suppressants and valvular heart disease. N Engl J Med 1998 Sep 10 339 765-766.

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