Valve Regurgitation Often Improves After Dexfenfluramine Discontinuation

Valve regurgitation as a result of fenfluramine or dexfenfluramine treatment often improves after patients discontinue therapy, according to results of two recent studies. Other patients remain stable, while only a few experience worsening valvular function.

Dr. James G. Jollis of Duke University Medical Center in Durham, North Carolina and colleagues compared echocardiograms obtained from 50 patients up to 981 days after discontinuing treatment with fenfluramine or dexfenfluramine. The patients were reassessed approximately 1 year later. Drug treatment had ranged from 65 to 1432 days, the investigators report in the Annals of Internal Medicine for February 20.

Initially, 38 patients exhibited at least mild mitral regurgitation, with severe regurgitation in 16 subjects. This improved by at least one grade in 17 patients and worsened in 2 patients. Mitral valve leaflet restriction, which was present in 30 patients at the first echocardiogram, improved in 11 patients and worsened in 2 patients. Similar results were observed among patients with aortic regurgitation.

The investigators note that improvement often involved multiple valves on both sides of the heart. There appeared to be no association between improvement and duration of drug treatment or time between echocardiograms.

Dr. Jollis and his associates conclude that surgical referral for patients with severe regurgitation may be delayed. Serial echocardiography, prophylaxis against endocarditis and medical therapy may be appropriate for patients who, even in the presence of severe regurgitation, have minimal symptoms and normal left ventricular function.

In another study in the same issue, Dr. Neil J. Weissman of the Washington Hospital Center in Washington, DC, and associates followed 914 patients who had been treated for 2 to 3 months with dexfenfluramine, its sustained-release formulation, or placebo. Paired echocardiograms videotaped from 1 to 3 months after treatment discontinuation and again 1 year later were compared.

The initial echocardiographs showed a prevalence of aortic regurgitation that was slightly higher in those who took dexfenfluramine. During the following year, aortic regurgitation increased in 0.7% of those who had taken either formulation of the drug, and decreased in 6.4% of those who received dexfenfluramine and in 5.1% of those who received sustained-release dexfenfluramine. There was no significant decrease in patients who received placebo.

According to editorialist Dr. Martin St. John Sutton from the Hospital of the University of Pennsylvania in Philadelphia, these findings “may be a silver lining to the dark cloud of anorexogen-related valvulopathy.”

Ann Intern Med 2001;134:261-273,335-337.