Treatment with digitoxin in addition to guideline-directed medical therapy reduces the risk of hospitalization for worsening heart failure (HF) or all-cause death compared with placebo in patients with HF with reduced ejection fraction (HFrEF). This finding comes from the DIGIT-HF trial, which was presented at the ESC Congress 2025 and simultaneously published in The New England Journal of Medicine.

Accordingly, Udo Bavendiek, Johann Bauersachs and colleagues conducted the double-blind, placebo-controlled DIGIT-HF trial, in which 1,240 patients with HFrEF were randomly assigned to receive digitoxin (starting dose of 0.07 mg daily) or placebo, in addition to guideline-directed medical therapy. During follow-up (median 36 months), a primary outcome event of all-cause death or admission to hospital for worsening HF occurred in 39.5% of patients in the digitoxin group compared with 44.1% of patients in the placebo group (HR 0.82, 95% CI 0.69–0.98, P = 0.03). Serious adverse events occurred in 4.7% and 2.8% of patients in each group, respectively.