A popular diet drug that was withdrawn from the market after being linked to serious heart problems may cause less significant damage than health officials first suspected--and in some cases the damage may be reversible, according to a study published last week.
Researchers at 15 medical centers around the country tracked 223 patients who took dexfenfluramine, also known as Redux. Redux was pulled from the market in 1997, along with its chemical cousin fenfluramine, a drug sold under the brand name Pondimin. Pondimin was typically taken along with phentermine, a combination known as fen/phen.
Two years ago the Food and Drug Administration, which approved Redux in 1996, reported that about 30 percent of 290 patients who took the drugs showed signs of heart valve problems. Several of these patients died after taking the drugs.
But the latest study, published last week in the journal Circulation and funded by Redux's Massachusetts-based manufacturer, Interneuron, found that 7.6 percent of 223 Redux users had valve problems compared with 2.1 percent of women who did not take the drug. The study also found that none of the cases of heart valve disease in the patients who took Redux was serious.
In addition, echocardiograms taken less than eight months after patients stopped taking Redux were twice as likely to reveal valve problems than were tests conducted eight months or more after discontinuation of the drug. This finding suggests that in some patients, valve damage may be reversible, said Bruce K. Shively, a cardiologist at Oregon Health Sciences University and the lead author of the study. But Shively cautioned that no study has examined the long-term effects of Redux.
Patients in Shively's study, who were matched with a control group of people who had not taken any diet drug for the previous five years, were moderately obese middle-aged women. One-third of them had hypertension and one-quarter were diabetic.
The characteristic that seemed clearly associated with valve problems was age, the researchers noted. Women over 60 were more likely to have a valve problem, while none of those under 60 did so.
This is not the first study to suggest that the risk posed by Redux and fenfluramine may be less severe and less common than previously believed. More than 18 million prescriptions for the drugs were written before they were withdrawn.
Last year Massachusetts researchers reported that two of 46 patients taking the drugs developed valve problems, but neither case was life-threatening. A study of 1,000 patients by researchers at the University of California at Irvine found only mild valve damage among patients who took Redux or fen/phen.
It is not clear why these recent results are at variance with the 1997 report of cardiologists from the Mayo Clinic, whose finding of heart valve damage in 24 fen/phen patients triggered withdrawal of the drugs. A spokesman for Mayo, based in Rochester, Minn., said its cardiologists were "not available" to discuss their findings or subsequent studies.
Shively said that he suspects that one reason for the difference may be selection bias in the Mayo patients--18 of whom were first treated at a clinic in Fargo, N.D.
"I think there is a tendency to over-report these things unless you take a random sample of the population," Shively said. "When you have millions of people who have taken these drugs, then anyone in that population who has a valve problem may be attributed to it."
"There is a definite risk to taking these drugs," Shively added, "but I think it's small and that serious problems are rare."
A little-noticed study by researchers at the University of Pennsylvania published in the August issue of the American Journal of Cardiology may shed some light on the Fargo cases. Stephen E. Kimmel and his colleagues examined the records of the 18 patients and found that seven of them had taken other drugs, such as a popular class of antidepressants, that could cause or contribute to heart valve problems. Four of the 18 had clinically documented heart murmurs before they began taking fen/phen, Kimmel wrote.
Since the withdrawal of the drugs, Redux and fen/phen have been the subject of frenzied litigation. Several months ago a Texas jury awarded $23 million to a woman who suffered serious heart problems after taking fen/phen; the case was settled for $2 million.
Recently American Home Products, which marketed Redux and Pondimin, agreed to pay $3.75 billion to settle class-action lawsuits brought by dieters who took the drugs. That settlement, which would be a record for the pharmaceutical industry if it is approved, is now pending. Last week a federal judge in Philadelphia gave preliminary approval to the class-action settlement.