Is It Time to Take a Second Look at Fen-Phen?

The appetite-suppressants fenfluramine and dexfenfluramine were withdrawn from the market late in 1997 after echocardiographic studies indicated that up to a third of users developed valvular heart disease (N Engl J Med 337:581, 1997). Harvard researchers now suggest that the incidence of valvular heart disease may be lower than previously suspected (Ann Intern Med 129:870, 1998).

Christina C. Wee, MD, and colleagues at Beth Israel Deaconess Medical Center and Harvard Medical School identified patients who used fenfluramine and dexfenfluramine for at least 14 days and who had echocardiographic studies done before they began taking the agents. They then compared the pretreatment echocardiograms with echocardiograms taken after therapy was discontinued. Of 873 patients identified as fenfluramine or dexfenfluramine users, 76 had echocardiography before the medications were started. This group was winnowed down to 34 who agreed to be interviewed by the authors.

Two of the 34 patients developed new or worsening valvular disease. Both were female and both had used Fen-Phen; neither used other diet medications or serotonergic agents. One had aortic valve disease at baseline.

The authors note that the relatively low risk for medication-associated aortic valve problems in their study shows the need for larger, carefully controlled studies to examine the true risks of long- and short-term use of fenfluramine and dexfenfluramine. Such studies might also evaluate the cost-effectiveness of routine echocardiography for former users of these diet medications.