Interpreting the DIGIT-HF trial: Time for a new look at digitalis?

The DIGIT-HF (Digitoxin to Improve Outcomes in Patients With Advanced Chronic Heart Failure; N Engl J Med 2025; 393(12):1155-1165) trial compared digitoxin with placebo, added to guideline-directed medical therapy in patients with heart failure with reduced ejection fraction (HFrEF). Compared with placebo, digitoxin reduced the incidence of the composite endpoint of death from any cause or first hospitalization for worsening heart failure by 18% over a median follow-up of 36 months (hazard ratio 0.82, 95% confidence interval 0.69-0.98). There were no statistically significant differences in the rates of all-cause mortality, first hospitalization, or serious adverse events.