Study Background and Disease Burden
Heart failure with reduced ejection fraction (HFrEF) remains a major contributor to morbidity and mortality globally, posing ongoing therapeutic challenges despite advances in guideline-directed medical therapy. The burden of HFrEF necessitates continued search for cost-effective, efficacious treatments that can improve survival and reduce hospitalizations. Historically, cardiac glycosides such as digoxin and digitoxin have been part of heart failure management; however, their use declined due to concerns over safety signals and the advent of newer agents. The DIGIT-HF trial was conceived to reassess the efficacy and safety of digitoxin when added to contemporary heart failure therapy in symptomatic patients with left ventricular ejection fraction ≤40%.
