Fen-Phen Study Raises Heart Valve Concerns
Raising concerns about the wildly popular weight-loss drug combination known as fen-phen, doctors at the Mayo Clinic have identified 24 women who developed damaged heart valves after taking the drugs, including five women who underwent heart surgery to repair or replace a defective valve.
It is the first time that a heart valve disorder, which gives rise to symptoms such as chest pain and shortness of breath, has been associated with fen-phen, a drug combination prescribed to some 18 million Americans last year. Previous studies have shown that fen-phen--short for fenfluramine and phentermine--increases the risk of very high blood pressure in the lungs, an extremely rare but sometimes fatal condition.
Although the Mayo Clinic analysis does not prove that fen-phen caused the heart valve damage in the patients studied, the findings prompted the Food and Drug Administration to warn doctors “because of the seriousness of the cardiac problems and their rare occurrence in otherwise healthy obese women.” The agency has been notified of an additional nine women in the United States with heart valve damage who took the drugs.
The findings are likely to send shock waves through the Southland, the world capitol of body image where one out of four people are nonetheless obese, meaning roughly 20% above their ideal weight. Moreover, the emerging fen-phen flap would seem to put patients in that dizzying modern quandary of balancing a treatment’s documented benefits against very serious but perhaps remote risks. Some 300,000 Americans a year die of complications of obesity.
Some researchers criticized the new study, which is due to be published next month in the New England Journal of Medicine, as misleading and incomplete.
“We’ve had over 1,000 patients [treated with fen-phen] and have not seen this problem at all,” said Dr. David Heber, director of the UCLA Center for Human Nutrition. “I believe this is an exaggeration of the underlying problems associated with this medication,” he said.
Fen-phen and other weight-loss drugs “make an invaluable contribution to helping patients lose weight when used responsibly,” he said.
The drug company Wyeth-Ayerst Laboratories, maker of fenfluramine, said the new study was “inconclusive” and that further studies “must be conducted before any possible link can be confirmed.”
Although the company is cooperating with the Mayo Clinic on additional studies, it pointed out in a statement that it was not clear how the new findings, which drew primarily on patients in Minnesota and North Dakota, applied to the rest of the country. It also suggested that the drug doses taken by some patients were higher than are usually prescribed.
Each of the drugs in the fen-phen combination has been approved by the FDA for weight-loss applications. But the agency has not approved the combination, chiefly because too few studies have been done on fen-phen’s safety and effectiveness. Fenfluramine and phentermine primarily suppress appetite. Each can cause side effects such as the jitters and diarrhea at the doses usually taken.
The fen-phen fad got started in the early 1990s after a University of Rochester study showing that the drugs could work when taken in combination at lower doses, giving rise to fewer side effects. Physicians began prescribing the drugs in combination even without FDA approval, an accepted practice known as “off-label” usage.
In the new report, medical researchers led by the Mayo Clinic’s Dr. Heidi Connolly document a heart valve disorder in two dozen women averaging 43 years old who had been on fen-phen for an average of one year and who had no previously known heart disease. The heart valve disorder was detected with a standard procedure, an echocardiogram.
Because the report is essentially a summary on patients who showed up in local clinics, the researchers cannot say how common the problem is among people consuming the drug. Indeed, they write, “definitive statements about a true association” between the medical problem and fen-phen “cannot be made.” But they say the problem is otherwise so uncommon in middle-aged women that the link to the drug combination “is not likely to be due to chance.”
In a separate statement, the Mayo Clinic researchers said that people currently taking the drug should “remain calm.” They said weight-reducing drugs might still be appropriate for some obese patients, including those who have failed to lose weight by cutting calories and exercising and who have complications of obesity that put them at risk of serious disease, such as diabetes, artery disease or high blood pressure.
The New England Journal of Medicine’s editors decided to lift the usual pre-publication embargo policy and let the Mayo Clinic researchers discuss the results now. “We think the message has a very significant public health importance,” said deputy editor Dr. Gregory Curfman. “I’m the first to admit that these are preliminary observations. We just don’t know how much more of this is out there.”
