Study Defines Link Between REDUX Diet Drug and Heart Valve Disease
11/22/99 Portland, Ore.
Recalled Drug Associated to Disease, But Conditions Not as Bad as First Thought
A comprehensive study of an anti-obesity drug taken by millions of Americans and removed from the market two years ago found a link to cardiac valve disease, but not as strong as first believed.
The study, led by Oregon Health Sciences University cardiologist Bruce Shively, M.D., will be published in the Nov. 23 issue of Circulation, the flagship scientific journal of the American Heart Association. Shively had served on the AHA's Council on Clinical Cardiology from 1996-98.
Dexfenfluramine, sold under the trade name Redux, is an anti-obesity medication that was taken off the market in September 1997 on the advice of the U.S. Food and Drug Administration because of concerns about its adverse effects on cardiac valves. It is closely related to fenfluramine, the "fen" in fen-phen, another drug that may cause valve disease.
The study found that dexfenfluramine, when taken for more than three months, is associated with mild aortic valve regurgitation, or moderate mitral valve regurgitation. Valvular regurgitation is the leakage of blood backward in the heart which, when moderate or severe, may increase the workload of the heart.
"We found that patients who took dexfenfluramine more than tripled their risk for abnormal valve regurgitation, although the overall risk is low," said Shively. His team found that 7.6 percent of the patients who had taken dexfenfluramine exhibited the valve disease, compared to 2.1 percent of those who had not taken the drug.
"The initial reports, including that of the FDA, suggested the frequency of valve disease associated with these diet drugs was going to be very high, perhaps greater than 30 percent," said Shively. "However, carefully controlled studies show that although a link is present, the frequency of significant problems is much lower."
Data for the study was collected from 412 patients at 26 sites in the United States who were grouped into matched pairs, half of whom had taken dexfenfluramine for an average of seven months, and half of whom had not. The pairs were matched based on gender, age, body mass index and treatment by the same physician. To determine the results of the study, three cardiologists from different university hospitals read each patient's echocardiogram without knowledge of whether the patient had taken the drug or the patient's medical background.
"Overall, most of the cases were mild. We found very few cases of moderate and none of severe regurgitation," says Shively.
In addition, the study identified other factors that influence the prevalence of valve regurgitation in dexfenfluramine patients. These factors included high blood pressure at the time of the echocardiogram and possibly other medications. Data from the study also indicate that the risk for valve regurgitation decreases as time passes after the patients stopped taking dexfenfluramine.
Although the diet drug is not being reviewed for reintroduction to the public, Shively says the data from this study are important for helping cardiologists to manage patients who have taken the drug in the past.
Further information on obesity and obesity-related topics can be found in the Heart and Stroke A-Z Guide at the American Heart Association's web site, www.americanheart.org.