Medications Considered Unsafe, Yale and Denver Health Medical Researchers Report
New Haven, Conn. — In a national study of diabetic patients hospitalized with heart failure, researchers from Yale University and Denver Health Medical Center found that more than a quarter are treated with diabetes medications not considered safe by the United States Food and Drug Administration (FDA).
Published in the July 2 issue of the Journal of the American Medical Association, the study showed that two popular types of diabetes medications-metformin and thiazolidinediones-are frequently used in patients with both diabetes and heart failure despite warnings against their use in this context. Metformin (Glucophage) is not recommended in patients requiring treatment for heart failure because such patients may be particularly susceptible to a serious condition called lactic acidosis.
Thiazolidinediones (Avandia or Actos) are not recommended for patients with significant heart failure symptoms because they may cause fluid retention and worsen symptoms. These warnings, approved by the FDA, are included in the package inserts for these medications.
Using data from the National Heart Care/National Heart Failure Project, a Centers for Medicare & Medicaid Services initiative to improve the care of Medicare patients hospitalized for heart failure between 1998 and 2001, the investigators studied the treatment of diabetes in more than 25,000 patients with heart failure. The researchers found that metformin or thiazolidinediones were prescribed to 13.5 percent of the patients in 1998-99. This practice nearly doubled-to 24.4 percent of patients-by 2000-01.
“The reasons for current patterns of treatment demonstrated in this study are unclear,” said senior author Harlan Krumholz, professor of medicine and director of the Yale-New Haven Hospital Center for Outcomes Research and Evaluation. “While it is possible that this practice reflects inadequate knowledge of the potential side-effects of these drugs, it is also possible that some physicians believe that the potential benefits outweigh the potential risks, despite the FDA warnings-and these physicians could be right.”
Frederick Masoudi, assistant professor of medicine at Denver Health Medical Center and the University of Colorado Health Sciences Center, and lead author on the study, said, “This study identifies a striking discordance between recommendations from the FDA and current practice patterns for the treatment of diabetes in patients with heart failure nationwide. Furthermore, the use of these drugs has increased dramatically over a relatively short period of time.”
Masoudi said that this study highlights the need for further data on the safety of using metformin and thiazolidinediones in patients with heart failure. “Additional research is urgently needed to determine whether this practice is safe. Until such data are available, physicians must either act contrary to the FDA recommendations or have fewer options for the effective treatment of diabetes in patients with heart failure.”
Although the care of patients with heart failure has been examined extensively, this study is one of the first to assess the approach to the care of conditions that commonly occur along with heart failure such as diabetes.
“Our findings have important implications for future research efforts,” said Krumholz. “A national surveillance system based upon large databases such as that used for this study could be helpful in assessing other patterns of care relevant to patient safety.”
Study authors include Masoudi, Krumholz, Yongfei Wang, statistical analyst, Yale University; Silvio Inzucchi, associate professor of medicine, Yale University; John Setaro, associate professor of medicine, Yale University, Edward Havranek, associate professor of medicine, Denver Health Medical Center and the University of Colorado Health Sciences Center; and JoAnne Foody, assistant professor of medicine, Yale University.