In 1997, the Digitalis Investigation Group trial found that treatment with digoxin did not decrease overall mortality among patients with heart failure but did decrease the risk of hospitalization for worsening heart failure. Rathore and associates conducted a post hoc subgroup analysis of the study data focused on sex-based differences in the outcome effects of digoxin therapy.
The analysis assessed 6,800 patients from the Digitalis Investigation Group study. These patients were randomly assigned to receive either digoxin or placebo and were followed for three years. The majority of patients were white, and only 22 percent of patients were women. Most patients had New York Heart Association functional class II or class III heart failure and were receiving 0.25 mg of digoxin daily. Compared with the male subjects, female participants were slightly older, had a slightly better ejection fraction, and were less likely to have an ischemic primary cause of congestive heart failure.
The three-year mortality rate among men was not significantly different in patients receiving digoxin and in patients receiving placebo (35.2 versus 36.9 percent, respectively). However, women receiving digoxin had a slightly higher mortality rate than those receiving placebo (33.1 versus 28.9 percent, respectively); this difference was of borderline statistical significance. Rates of hospitalization were decreased in both sexes with the use of digoxin, but the effect was more profound in men (-8.9 percent) than in women (-4.2 percent).
The authors conclude that their findings of increased mortality and a smaller reduction in the rate of hospitalization in women “raise strong concern about the appropriate role of digoxin therapy in women.”
editor’s note: Most clinical guidelines for heart failure advocate the use of digoxin; however, most practicing physicians are aware of the continuing clinical controversies surrounding this medication. The differences in cardiac disease between men and women have received a fair amount of press and medical attention in recent years. It is worth noting that the 95 percent confidence intervals for the mortality difference between digoxin and placebo in this study included zero for both men and women. Therefore, it is possible that the small differences in death rates for both sexes could be caused entirely by chance. While the media may trumpet the injurious effects of digoxin in women, physicians should be mindful of the statistical pitfalls in these reports.—b.z.