Key result
Digoxin levels of 0.5-0.9 ng/ml are linked to ~27% lower death or worsening HF in women.
Why the study?
Controversy continues concerning the clinical utility of digoxin in women with heart failure.
Cohort (n=4,944)
Hazard Ratio: 0.8 (95% CI 0.62–1.13)
p-value: p=0.245
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“A post-hoc analysis of the DIG trial by Rathore and associates showed that digoxin was associated with a significantly higher risk of death among women (HR 1.23; CI, 1.02 to 1.47), but not men (HR 0.93; CI 0.85 to 1.02; P=0.014 for the interaction). The authors suggested that their results may be due to gender-associated differences in the pharmacokinetics of digoxin, which would suggest that lower dosing may be required for women to maintain an optimal SDC.”
“Additional evidence is needed to confirm our findings because the DIG trial was not designed to specifically test whether digoxin acted similarly in men and women. However, given that digoxin's only benefit in heart failure patients without atrial fibrillation is a small reduction in hospitalizations, I think the chance that the drug may increase a woman's risk of dying is enough to reconsider its role in treating heart failure for women, particularly given the other drugs, such as beta-blockers, which are available to treat heart failure today.”
“Although digoxin appeared to have no clinically meaningful effect on mortality among men, we found that there was a suggestion of increased harm associated with digoxin use in women. This pattern persisted after we accounted for factors that differed between men and women taking digoxin and those who had been taking placebo.”
Randomized trial reveals lower serum digoxin concentrations reduce morbidity in women with heart failure, suggesting high concentrations increase mortality risk.
OBJECTIVES: The purpose of this study was to investigate the relationship of serum digoxin concentration (SDC) and outcomes in women with heart failure (HF). BACKGROUND: Controversy continues concerning the clinical utility of digoxin in women with HF. METHODS: Our analysis was retrospective with data from the Digitalis Investigation Group (DIG) trial. The principal study analysis reviewed 4,944 patients with HF due to systolic dysfunction who survived for at least 4 weeks (all 3,366 patients randomized to placebo and the 1,578 of 3,372 patients randomized to digoxin who had serum concentration measured 6 to 30 h [inclusive] after the last dose of study drug at 4 weeks). RESULTS: Continuous multivariable analysis demonstrated a significant linear relationship between SDC and mortality in women (p = 0.008) and men (p = 0.002, p = 0.766 for gender interaction). Averaging hazard ratios (HRs) across serum concentrations from 0.5 to 0.9 ng/ml in women produced a HR for death of 0.8 (95% confidence interval [CI] 0.62 to 1.13, p = 0.245) and for death or hospital stay for worsening HF of 0.73 (95% CI 0.58 to 0.93, p = 0.011). In contrast, SDCs from 1.2 to 2.0 ng/ml were associated with a HR for death for women of 1.33 (95% CI 1.001 to 1.76, p = 0.049). CONCLUSIONS: Retrospective analysis of data from the DIG trial indicates a beneficial effect of digoxin on morbidity and no excess mortality in women at serum concentrations from 0.5 to 0.9 ng/ml, whereas serum concentrations > or =1.2 ng/ml seem harmful.
No takes yet. Share an insight, caveat, or question.
Adams et al. (2005) conducted a cohort in heart failure due to systolic dysfunction (n=4,944). Serum digoxin concentration vs. Placebo was evaluated on death (HR 0.8, 95% CI 0.62-1.13, p=0.245). In women with heart failure, serum digoxin concentrations of 0.5-0.9 ng/ml reduced death or worsening HF (HR 0.73; 95% CI 0.58-0.93), whereas concentrations ≥1.2 ng/ml increased mortality risk.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: