[Digitalis for heart failure: welcome back?]

The use of cardiac glycosides (digitalis) for the treatment of heart failure with reduced ejection fraction (HFrEF) has steadily declined in the era of modern prognosis-improving pharmacotherapy, given the lack of conclusive evidence from clinical trials.

The evidence for the use of cardiac glycosides in HFrEF is presented based on both earlier and recent clinical trials, with corresponding recommendations.

The recently published DIGIT-HF trial demonstrated that low-dose digitoxin (serum concentrations of 8-18 ng/ml) reduced the primary outcome of all-cause death and heart failure hospitalizations in patients with symptomatic HFrEF well treated with guideline-recommended medical therapy. Patients with low blood pressure and higher heart rates appeared to derive particular benefit. This positive treatment effect was independent of age and sex as well as the presence of atrial fibrillation or impaired renal function. In contrast, digoxin did not significantly affect the primary outcomes in the earlier DIG or the recently completed DECISION trial, the latter involving low-dose digoxin and contemporary heart failure pharmacotherapy. Both trials demonstrated nominally favorable effects for digoxin on heart failure hospitalizations/visits (secondary outcome), which was further supported by a meta-analysis incorporating data from all three trials.

Digitoxin (at low serum concentrations) is recommended for patients with HFrEF and persistent symptoms despite standard therapy, since, in contrast to digoxin, there are positive trial data demonstrating a reduction in mortality and heart failure hospitalizations.