Popular Heart Failure Drug May be Dangerous for Women, Yale Researchers Report

Digoxin, a drug commonly used to treat patients in heart failure, may pose an increased risk of death for women, according to researchers at Yale School of Medicine.

Published in the October 31 issue of the New England Journal of Medicine, the study showed that digoxin had a different effect on men than women. Although digoxin had no effect on the risk of death in men, women who were taking the drug had a higher risk than women who were taking a placebo (33.1 percent versus 28.9 percent). After accounting for other characteristics that differed between women who were taking digoxin and those who were not, digoxin significantly increased women’s relative risk of death by 23 percent.

“These data suggest that digoxin acts differently in men than women,” said Harlan Krumholz, professor of medicine at Yale School of Medicine, director of the Yale-New Haven Hospital Center for Outcomes Research and Evaluation, and the senior author on the study.

“Although digoxin appeared to have no clinically meaningful effect on mortality among men, we found that there was a suggestion of increased harm associated with digoxin use in women,” said the study’s first author, Saif Rathore, lecturer in the Department of Internal Medicine. “This pattern persisted after we accounted for factors that differed between men and women taking digoxin and those who had been taking placebo.”

The study team used data from the Digitalis Investigation Group (DIG) Trial, a National Heart, Lung, and Blood Institute-sponsored trial of digoxin that was conducted between 1991 and 1996. The DIG trial’s main results had shown that digoxin was similar to placebo in terms of reducing mortality, but did decrease patients’ risk of hospitalization over an average of 37 months of follow-up.

Digoxin, also marketed as Lanoxin, is one of the most commonly prescribed medications in the United States. “More than 25 million prescriptions for digoxin are filled in the United States each year. Although some of these are for patients who have atrial fibrillation, a heart rhythm disorder, we think a large proportion of these are for patients with heart failure, and presumably half are being filled by women,” Rathore said.

Krumholz said the findings have important implications for clinical practice. “Additional evidence is needed to confirm our findings because the DIG trial was not designed to specifically test whether digoxin acted similarly in men and women,” he said. “However, given that digoxin’s only benefit in heart failure patients without atrial fibrillation is a small reduction in hospitalizations, I think the chance that the drug may increase a woman’s risk of dying is enough to reconsider its role in treating heart failure for women, particularly given the other drugs, such as beta-blockers, which are available to treat heart failure today.”

“Women with heart failure who are taking digoxin should talk with their physicians about whether they should continue with this drug,” Krumholz said.

In addition to Krumholz and Rathore, Yongfei Wang, statistical analyst in the Department of Internal Medicine, was an author of the study.

(The National Heart, Lung, and Blood Institute issued this disclaimer: The Digitalis Investigation Group study was conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the Digitalis Investigation Group Investigators. This study was not prepared in collaboration with the investigators of the Digitalis Investigation Group and does not necessarily reflect the opinions or the views of the Digitalis Investigation Group or the NHLBI.)

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