Ahmed A et al. (2006) Digoxin and reduction in mortality and hospitalization in heart failure: a comprehensive post hoc analysis of the DIG trial. Eur Heart J 27: 178–186

The DIG trial showed that digoxin reduced heart-failure (HF)-related hospitalizations, but not overall mortality, in HF patients with ejection fraction (EF) ≤45%. Low serum digoxin concentrations (SDCs) are associated with reduced mortality, but this correlation has not been demonstrated in patients with EFs >45%. Ahmed et al. investigated the effects of digoxin on all-cause mortality and HF-related hospitalization in HF patients with a range of EFs and SDCs.

This comprehensive post hoc analysis focused on 5,548 DIG trial patients receiving either placebo (n = 3,861) or digoxin at ≤0.125 mg/day, 0.25 mg/day or >0.25 mg/ day. Of the 1,687 digoxin-treated patients for whom data were available, 982 were classified by the authors as having low SDC (0.6–1.2 nM [0.5–0.9 ng/ml]) and 705 were classified as having high SDC (≥1.3 nM [1.0 ng/ml]).

KAPLAN–MEIER ANALYSIS and multivariate analysis showed that, compared with placebo, low SDC was associated with a significantly reduced risk of death (P <0.0001). HF-related hospitalization was significantly less likely in both low and high SDC patients than in placebo patients (P <0.0001 and P = 0.006, respectively); low SDC also reduced risk of all-cause hospitalization (P <0.0001). Factors predicting high SDC included increased age, female sex, diuretic use and digoxin dose ≥0.25 mg/day.

The authors conclude that digoxin, in addition to reducing HF-related hospitalization in chronic HF patients, also reduces all-cause mortality and all-cause hospitalization if given at doses that achieve an SDC of 0.6–1.2 nM. They recommend that digoxin should be used more widely at such doses in HF patients.