In a an article published in the October 31, 2002 issue of the New England Journal of Medicine, researchers report that treatment with digoxin may increase the rate of death in women with heart failure. This finding is regarded as surprising, as digoxin (and similar drugs in the digitalis group) are some of the oldest and most revered drugs in common usage for patients with heart failure, and it has stirred up strong feelings among cardiologists.
The authors, who are from Yale University, reached this startling conclusion after examining data from a previously-published clinical trial: the Digitalis Investigation Group (DIG) trial. In the DIG trial, men and women with heart failure were randomized to receive either digoxin or a placebo. The main findings of the DIG trial were that digoxin does not improve mortality in patients with heart failure, but it does seem to reduce the need for hospitalization in those patients. However, when the investigators later looked at gender-specific responses to digoxin, they found that women in the DIG trial who received digoxin had a 4% increase in cardiovascular death, as compared to women taking placebo.
Some have argued that the higher death rate in women might be just a statistical aberrancy, since the DIG study was not designed to examine gender differences in the response to digoxin,and doing the gender-specific analysis was done as an afterthought.
However, it may actually be true that digoxin is simply more dangerous in women than in men; that is, perhaps women are just more sensitive to digoxin.
What are doctors doing about digoxin in women?
Who knows? Quite possibly nothing, since the "experts" can't agree on its meaning.
The scientific bodies that devise official guidelines for the treatment of heart failure, for instance, will simply not be able to make a strong statement about using digoxin in women, since they do not pay much attention to post hoc data analyses. (There are sound statistical reasons for them to adopt this policy.) So it is unlikely that the guidelines, or physician habits, will be changed on the basis of this new finding. So it is unlikely that most doctors have changed their previous habits.
What should women with heart failure do if their doctor prescribes digoxin?
Women with heart failure do not labor under the same statistical constraints as scientific deliberative bodies. What they need to know is: what is likely to be the best thing for ME? These women need to keep in mind that only 20% of the controversy among doctors about this new finding is due to the fact that digoxin may be useful in some patients with heart failure. The other 80% is due to the fact that doctors are used to prescribing digoxin for heart failure, whether it does any good or not, and along comes a study messing with tradition. A controversy is to be expected.
In any case, here is what women with heart failure need to know about the use of digoxin:
- At best, the benefits from using digoxin in heart failure are relatively marginal; that is, digoxin may provide a modest reduction in the need for hospitalization.
- At worst, digoxin might substantially increase the risk of death.
- In the modern era, even taking the results of the DIG trial at face value, there are far more effective treatments for heart failure than digoxin. If beta blockers, ACE inhibitorsand diuretics are used to their full potential, it is likely that digoxin will not be needed (and may not be additionally effective) at all.
- According to every survey that has been done, beta blockers and ACE inhibitors (both of which not only improve symptoms but also increase survival) are grossly underutilized by doctors treating heart failure.
- Using digoxin in women with heart failure before beta blockers and ACE inhibitors have been added, and their doses maximized, probably ought to be considered bad medicine (since at the least it suggests the doctor is not well-versed in the modern treatment of heart failure.)
- If the use of beta blockers, ACE inhibitors and diuretics has been maximized, and full consideration of cardiac resynchronization therapy has been given, then (and only then) is it reasonable to consider adding digoxin in a woman with heart failure who has continuing symptoms. Only when you get to this point do you actually need to worry about the possible increase in mortality caused by digoxin.
By following this logic tree, women with heart failure will only rarely need to be concerned about a digoxin-induced mortality risk. Much more commonly, they will need to concern themselves with finding a doctor who actually knows what he/she is doing in the management of heart failure.
