Q&A

Digoxin increases mortality among women with congestive heart failure

J Fam Pract. 2003 February;52(2):94-117
By
Sharon See, PharmD
Patricio Bruno, DO, St.
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  • BACKGROUND: Is there a difference in the effect of digoxin for heart failure between women and men? This study is a subgroup analysis of the Digitalis Investigaton Group Trial (DIG), which, in 1997, showed that digoxin did not affect mortality in the treatment of heart failure. This subgroup analysis reexamined the data and looked for sex-based differences, which is important because women account for the majority of deaths from congestive heart failure.
  • POPULATION STUDIED: The researchers from the original DIG trial enrolled 6800 patients who had stable heart failure with an ejection fraction of 45% or less and who were in normal sinus rhythm. Overall, the women in the study were older than the men, had a shorter duration of heart failure, had a higher median ejection fraction, and had greater disease severity as classified by the New York Heart Association system. The reported results, however, adjust for these differences.
  • STUDY DESIGN AND VALIDITY: This is a post hoc analysis of the DIG trial, a randomized, double-blinded, placebo-controlled study of 5281 men and 1519 women randomized to receive either digoxin or placebo. This reanalysis of the DIG data looked at the outcomes separately for men and women.
  • OUTCOMES MEASURED: The primary outcome was death from any cause within an average of 37 months (range 24 to 48 months). Other outcomes included death from cardiovascular disease, death from worsening heart failure, and hospitalization for heart failure.
  • RESULTS: The investigators reported that women on digoxin had a significantly higher mortality compared with men (33.1% vs 35.2%, P=.034). Mortality was not significantly higher in women receiving digoxin compared with women receiving placebo (33.1% vs 28.9%, respectively; 95% confidence interval [CI], 20.5 to 8.8). However, after adjusting for other factors (eg, age, race, ejection fraction), digoxin use was associated with a significant increase in mortality in women compared with men (hazard ratio 1.23; 95% CI, 1.02–1.47; number needed to harm=22; 95% CI, 11–227).
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PRACTICE RECOMMENDATIONS

Digoxin increases mortality in women with congestive heart failure, compared with men; however, the clinical significance of this is unknown since gender is a nonmodifiable risk factor. More importantly, there is a suggestion of harm when looking at women treated with digoxin versus placebo. Since there are other therapies with definite benefit in congestive heart failure (angiotensin-converting enzyme inhibitors, beta-blockers, spironolactone), it is prudent to reconsider the use of digoxin in women with ejection fractions less than 45%.

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