Abstract Body (Do not enter title and authors here): Background
The therapeutic efficacy of the cardiac glycoside digitoxin among patients with heart failure (HF) and reduced ejection fraction (HFrEF) is not established. The DIGIT-HF trial investigated the efficacy and safety of digitoxin versus placebo in patients with HFrEF. Here, we examined the effects of digitoxin according to age.
Methods
DIGIT-HF is a randomized, double-blind, placebo-controlled, multicenter trial enrolling patients with symptomatic HFrEF (New York Heart Association [NYHA] class ≥ II and left ventricular ejection fraction [LVEF] ≤ 30%, or NYHA class ≥ III and LVEF ≤ 40%). Patients were randomized to digitoxin or placebo on top of standard of care. The primary outcome was a composite of time to all-cause death (ACD) and hospital admission for worsening HF (HFH). Key secondary outcomes were time to ACD (non-inferiority) as well as the rate of recurrent HFH and ACD.
Results
A total of 1240 patients were randomly assigned to receive either digitoxin or placebo, and a total of 1212 patients fulfilled the criteria of the intention-to-treat population. Patients were on average 66 years old with 20% being women and 27% suffering from atrial fibrillation. Mean LVEF was 29% and HF symptom burden was high (NYHA class ≥III 70%). The mean estimated GFR was 65 ml/min/1.73 qm. Patients had a well-implemented contemporary pharmacologic HF therapy and a high treatment rate with implantable cardioverter defibrillator- and cardiac-resynchronisation-therapy-devices. Patients were divided in four age categories based on quartiles: age ≤ 59 years (n=335, 27.6%; median 54), age 60-66 years (n=279, 23.0%; median 64), age 67-75 years (n=302, 24.9%; median 71), age > 75 years (n=296, 24.4%; median 79 ). Baseline parameters of the age groups between the treatment groups were well balanced (Table 1-3). With proceeding age, HF symptom burden (NYHA), rates of atrial fibrillation and parameters of ischemic heart disease were increased, whereas kidney function was worsened. Treatment rates with angiotensin receptor-neprilysin inhibitors, mineralocorticoid-receptor-antagonists, sodium-glucose cotransporter 2 inhibitors as well as implantable cardiac defibrillators were lower with increasing age.
Effects of digitoxin on outcomes according to age will be added after publication of main trial results (accepted presentation ESC Congress 2025, manuscript under review at renowned medical journal, current embargo).
Conclusions
To be added after publication of main trial results.