In the largest study of its kind, Duke University Medical Center researchers found that the longer a person used a popular duet of diet drugs known as “fen/phen,” the greater the likelihood they had a heart valve abnormality.
Duke researchers said in a report prepared for the annual meeting of the American College of Cardiology that they found evidence on a cardiac diagnostic test of “mild or greater aortic regurgitation” in 8.8 percent of 1,163 patients who used fen/phen for three months or more. In comparison, they detected the same problem in 3.6 percent of a control group of 672 overweight people who had not taken the drug.
In a study funded by Wyeth-Ayerst Laboratories, makers of the “fen” in fen/phen, the research team determined that the prevalence of this valve problem was related to the duration of time the drug was used. Among those who used the diet drug combo for less than six months, there was no increase in mild or greater aortic regurgitation, but “the longer people in this study took the drugs, the greater the likelihood that they showed some abnormality on an echocardiogram,” said Duke cardiologist Dr. Thomas Ryan.
He added that most of the cases of aortic regurgitation noted by the research team were graded as “trace or mild. In our clinical experience, most patients with mild aortic regurgitation have few if any symptoms because the heart can compensate for this leakage,” Ryan said.
Aortic regurgitation occurs when blood leaks from the aorta — the large artery that distributes blood to the body — back through the aortic valve into the left ventricle, the heart’s main pumping chamber. Ryan said that while the likelihood of developing the leaking valve increased the longer a person took fen/phen, it didn’t mean the problem became more and more severe over time.
Ryan also said that the Duke cardiology team noted a statistically significant increase in shortness of breath during exercise in study patients who used fen/phen (26 percent) compared to patients who didn’t (21 percent). Shortness of breath is not associated with the regurgitation, however, so the relationship between that finding and use of the drug isn’t clear, he said.
The “fen” in fen/phen refers to fenfluramine. It and a similar drug were withdrawn in September 1997 due to reports of heart-valve problems among a small percentage of the 4 million people who took the fen/phen combination.
Ryan said in an interview that results of the new study are similar to several smaller studies on fen/phen use that have been reported in the last year. The difference in this study is that more patients were included, and the study was designed to examine duration of drug use. To help them make their analyses, the researchers used an echocardiogram taken on all the patients. An echocardiogram is a diagnostic test that uses ultrasound to picture both a heart’s structure and how blood flows into, within, and out of the heart.
Medical information on the 1,163 patients who used fen/phen for more than three months was gathered from 33 different diet clinics around of the country. Among other conclusions, the researchers found:
no significant difference in the incidence of aortic valve regurgitation in people who used the drug for three to six months, compared to the control group.
no significant difference in the prevalence of regurgitation in the mitral valve between the two groups. Mitral valve regurgitation was noted in 2.5 percent of the diet drug patients compared to 1.5 percent in the control group. The mitral valve controls the flow of blood between the left atrium, where blood is received from the lungs, and the left ventricle, the pumping chamber.
While Ryan considers the study the most definitive to date, he noted that it had to rely on retrospectively collected information – it was not a randomized, prospective clinical trial – and that there were gender and racial differences between the group that used drugs and the group that didn’t. For example, there were more white women in the treated group compared to the control group. “It’s the best study that can be done given the nature of the issue,” he said.
Working with him on the study were, from Duke, cardiologists Dr. James Jollis, Dr. Carolyn Donovan and Dr. Joseph Kisslo, and from Wyeth-Ayerst, Dr. Ginger Constantine and Dr. Kelly Davis.