DIGitoxin to Improve ouTcomes in patients with advanced chronic Heart Failure (DIGIT-HF): Baseline characteristics compared to recent randomized controlled heart failure trials

Abstract

Aims: This report presents the baseline characteristics of patients enrolled in the DIGIT-HF trial and compares them with participants from recent trials with improved outcomes in patients with heart failure (HF) and a reduced ejection fraction (HFrEF).

Methods and results: DIGIT-HF, a randomized, double-blind, placebo-controlled, multicentre trial enrolling patients with symptomatic HFrEF (New York Heart Association [NYHA] functional class II and left ventricular ejection fraction [LVEF] ≤30%, or NYHA class III-IV and LVEF ≤40%), compares the efficacy and safety of digitoxin versus placebo in addition to standard treatment. Most baseline characteristics of the intention-to-treat population (1212 patients, mean age 66 ± 11 years, 20% women, mean LVEF 29 ± 7%) were similar to those in recent HFrEF trials. The distribution of NYHA class II, III, and IV was 30%, 66% and 4%, respectively, and indicates that the patients were sicker than in comparator HFrEF trials. Less patients had atrial fibrillation (27%) than those in recent HFrEF trials, but prescription rates of background therapy with beta-blockers (96%), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors (95%), mineralocorticoid receptor antagonists (76%), and diuretics (87%) were high and similar. Overall, 40% of patients were on angiotensin receptor-neprilysin inhibitors, 19% on sodium-glucose cotransporter 2 inhibitors, and 9% on ivabradine. Rates of implantable cardioverter-defibrillator (ICD, 64%) and cardiac resynchronization therapy (CRT, 25%) devices were much higher than in recent HFrEF trials.

Conclusions: Patients included in DIGIT-HF display a more severe HF symptom burden and higher rates of ICD/CRT implants compared to participants in recent HFrEF trials, while pharmacotherapy was largely similar.

Clinical trial registration: EudraCT (2013-005326-38).

Keywords: Cardiac glycosides; Digitoxin; HFrEF; Heart failure; Randomized clinical trial.

Figure 1

(A) New York Heart Association (NYHA) class in % of trial population. (B) Concomitant medication in % of trial population. (C) Device use in % by trial population. ACEi, angiotensin‐converting enzyme inhibitor; ARB, angiotensin receptor blocker; ARNI, angiotensin receptor–neprilysin inhibitor; BB, beta‐blocker; CRT, cardiac resynchronization therapy; ICD, implantable cardioverter‐defibrillator; MRA, mineralocorticoid receptor antagonist. *In PARADIGM‐HF ~50% of patients were allocated to ARNI per protocol.