WEDNESDAY, Oct. 30, 2002 (HealthDayNews) -- A new analysis of a study that led to government approval of digitalis as a treatment for heart failure has raised the disturbing possibility that the drug does more harm than good for women.
Women given the drug, also known as digoxin, in the Digitalis Investigation Group (DIG) trial in the 1990s had a 23 percent higher risk of death than women given placebo, an inactive substance, says a report in tomorrow's issue of The New England Journal of Medicine. There was no comparable effect on the risk of death in men.
"For every 25 women treated with digoxin, there was one extra death," says Dr. Harlan Krumholz, a professor of medicine at the Yale School of Medicine and senior author of the study.
The finding, together with the limited benefit of the drug, is a compelling argument against the use of digoxin in women with heart failure, Krumholz says. The DIG trial found no overall reduction in deaths from heart failure, but there was a reduction in the number of hospitalizations, he notes.
Digitalis is derived from the foxglove plant. While digoxin drugs have been used since the 18th century, the U.S. Food and Drug Administration (FDA) gave approval for its use against heart failure only after the DIG trial was done.
"This subanalysis of the DIG trial raises the question of the safety and efficacy of digoxin in women," Krumholz says. "It does not say definitively that it is harmful, but it definitely says we do not know that it is safe and effective."
Cardiologists should turn to other drugs known to be effective in heart failure, such as ACE inhibitors and beta blockers, Krumholz says. From his point of view, digoxin is often used because it has been a part of medical practice for many decades. "Physicians over time become very used to the medication, while others that are known to be beneficial are underused," he says.
A different view is expressed by Dr. Mihai Gheorghiade, a professor of medicine at Northwestern University Medical School and co-author of an accompanying commentary. The new analysis "raises a hypothesis that needs to be tested," he says. "It is raising an important issue but not giving us conclusive data to adjust our clinical practice."
One obvious cause of the differing results among men and women is that women usually weigh less, Gheorghiade says. The digoxin dose was not adjusted for body weight in the DIG trial. "Women have smaller bodies, so if you use the same dose for men and women, it may have a different effect," he says.
Guidelines issued by the American Heart Association and other organizations take body weight into account, Gheorghiade says. "The guidelines suggest a low dose, period," he says.
The new finding "is not going to change the way I practice, but it will make me pay more attention to the dose I use," he says. "The message is that if you have women patients, make sure that if you use digoxin, the dose is very low -- the lowest dose possible."
However, Krumholz maintains the difference in body weight is not enough to account for the finding. "We can speculate about the mechanisms, but the truth is that we don't know what are the mechanisms," he says. "The question is where you put the burden of proof. We should take a step back and not use this drug in this setting because of this potential risk. If we came to the FDA today with this kind of data, I don't think they would approve it."
"Perhaps the reduction in the rate of hospitalization for heart failure among women could have been achieved without an increase in mortality if a lower dose had been used," Gheorghiade counters. "We should not abandon a therapy that may help women with heart failure."
What To Do
You can learn more about digoxin and its relatives from the National Library of Medicine. Learn about heart failure from the American Heart Association.
