DALLAS, Nov. 23 -- More evidence has been found linking the anti-obesity drug dexfenfluramine with damage to heart valves, but the new research suggests that the problems are typically not severe and may regress after the drug is discontinued, according to today's Circulation: Journal of the American Heart Association.
None of the patients in the study who took dexfenfluramine had severe mitral valve disease or moderate or worse aortic valve disease. However, 7.6 percent of the treated patients had either mild aortic valve disease or moderate mitral valve problems compared to 2.1 percent for individuals who did not take the drug.
Researchers used echocardiography to determine the frequency and severity of heart valve leakage, imaging the heart an average of 8.5 months after individuals stopped taking dexfenfluramine.
The chances of detecting a valve problem were related to the length of time from drug cessation. Valve problems were detected at twice the rate among patients who had stopped treatment less than eight months before their echocardiogram compared to those who had been off the medicine for longer than eight months.
"This indicates the possibility of regression," says the study's lead author Bruce K. Shively, M.D., associate professor of cardiology at Oregon Health Sciences University, Portland.
Dexfenfluramine is an appetite suppressant very similar to fenfluramine, which combined with the diet drug phentermine became the popular anti-obesity treatment known as fen/phen. It has been estimated that in 1996, the total number of prescriptions for dexfenfluramine or fenfluramine and phentermine in the United States exceeded 18 million.
The diet products containing fenfluramine and dexfenfluramine were taken off the market following reports that showed a link between diet drugs and damage to the heart valves. If the heart valve is damaged it either cannot open properly or fails to close all the way and lets blood leak backward. Many healthy adults have very mild backward leakage of blood through the valve. However, severe heart valve damage can be life-threatening.
This latest study looked at the prevalence and severity of valve disease in 223 patients, recruited from 26 centers in 15 states, who had taken dexfenfluramine for an average of seven months. Those patients were compared to a control group of 189 people who did not take the diet drug, which in part reduces a person's appetite by affecting serotonin, a chemical in the brain that makes people feel full.
"The study strongly suggests that dexfenfluramine is associated with valve disease," Shively says. "However, the frequency is not very high and the severity is usually mild. It is important to remember that no study yet has looked into the long-term effects."
Shively says there was no relationship in this study between the amount of time a patient took the diet drug and their risk of heart valve problems. Since the study included very few patients treated less than three months, it is not conclusive about the relationship between the duration of treatment and valve disease.
"This study was highly controlled, which means that patients were closely matched to controls for characteristics that affect valves to show only the effect of dexfenfluramine. Patients in the study were treated for a mean of seven months, which is typical of how long the drug was taken by people in the United States. We also could determine the factors that might influence the frequency and severity of valve disease in patients taking the diet drug," says Shively.
In addition to being treated at the same medical sites, the control group was matched to the treatment group for age, sex and body mass index, a measure of obesity, Shively says. Further, neither patients nor individuals in the control group took other diet drugs within five years.
Co-authors are Carlos A. Roldan, M.D.; Edward A. Gill, M.D.; Thomas Najarian, M.D., and Sonja Barton Loar, Pharm.D.