Digoxin is used in patients with HF and the rate of hospitalisations in that population is reduced according to the Digitalis Investigation Group study. Post hoc analysis of Digitalis Investigation Group indicated that digoxin, when used in the treatment of HF, may increase mortality by approximately 20% in women but not in men. Further randomised trials evaluating the interaction between digoxin and sex have not emerged.
It remains unclear whether digoxin should be used differently in the different sexes, and concerns about its use in women continue to appear in the literature. This study is to assess whether digoxin has a different effect on mortality risk for women than it does for men in patients with heart failure (HF).
This study uses the database of UK-based The Health Information Network population in a cohort study of the impact of digoxin exposure on mortality for men and women who carry the diagnosis of HF. Digoxin exposure was assessed based on prescribing data. Multivariable Cox proportional hazards models were used to assess whether there was an interaction between sex and digoxin affecting mortality hazard.
The study cohort consisted of 17?707 men and 19?227 women with the diagnosis of HF who contributed only time without digoxin exposure and 9487 men and 10?808 women with the diagnosis of HF who contributed time with digoxin exposure.
The absence of a large interaction between digoxin use and sex affecting mortality is the primary outcome of this study. Digoxin use was associated with a HR for mortality of 1.00 for men, while for women, the HR was also 1.00 (p value for interaction 0.65).
The results of sensitivity analyses were consistent with those of the primary analysis. There was no evidence of a different association between digoxin use and mortality in women compared with men. Sensitivity analyses did not affect this estimate materially. An interesting incidental finding of this study is that interventions known to reduce mortality in HF are used less in women than in men who have been diagnosed with HF.
The study did not identify a difference between the sexes in the hazard of death associated with the use of digoxin. These results are of use in the context of a clinical question that whether digoxin can be used as safely in women as it can in men, for which there are few randomised data. These results suggest that this drug, with its proven ability to reduce the need for hospitalisation, is still a viable therapeutic option in women with HF.
Observational data do not support the concern that there is a substantial increased risk of mortality due to the use of digoxin in women. This finding is consistent with previous observational studies but discordant with results from a post hoc analysis of a randomised controlled trial of digoxin versus placebo.