Real-life indications to digitoxin treatment in patients with heart failure and reduced ejection fraction

Background

The role of cardiac glycosides in the management of heart failure with reduced ejection fraction (HFrEF) is uncertain. Current guidelines recommend their use in patients with persistent symptoms despite optimized guideline-directed medical therapy (GDMT) or for rate control in those with concomitant atrial fibrillation (AF). The DIGIT-HF trial has renewed interest in digitoxin in patients with HFrEF, but real-world data on patient eligibility for digitoxin in contemporary heart failure (HF) populations are lacking.

Purpose

To assess eligibility for digitoxin in a real-world population of patients with HFrEF, followed in a tertiary outpatient HF clinic.

Methods

Patients attending our HF clinic between November 2024 and November 2025 were screened for inclusion. Eligibility for digitoxin was assessed according to the inclusion and exclusion criteria of the DIGIT-HF trial.

Results

Among 1.427 outpatients attending the HF clinic over the study period, 257 patients (age 72 ± 4.8 years, 69% male) with HFrEF were included for eligibility assessment (Figure 1). Most patients were in NYHA class II (61.5%), with a mean left ventricular ejection fraction (LVEF) of 32 ± 6.3%. Most patients were treated with a beta-blocker (86.0%), a mineralocorticoid receptor antagonist (76.7%), a sodium–glucose cotransporter 2 inhibitor (72.9%), and any renin-angiotensin-aldosterone system inhibitor (67.7%). 57% of patients had a defibrillator-based device (ICD or CRT-D). Hypertension (77.0%), chronic kidney disease (CKD, 50.2%) and diabetes (DM, 38.1%) were the most common comorbidities. AF was present in 26.8% of the population.

Estimated eligibility for digitoxin was 18.7%. Inclusion criteria (met by 30.7% of the population) had a greater impact on eligibility than exclusion criteria (88.3% of the population would have been eligible after applying exclusion criteria alone). The main inclusion criterion limiting eligibility was the combination of LVEF ≤ 40% and NYHA class I-II (met by 60.3% of the population). Without this criterion, 91% of the HFrEF population would have been eligible for inclusion. The three exclusion criteria most frequently limiting eligibility were: (1) recent (< 2 month ago) acute coronary syndrome, coronary revascularization, valve intervention, stroke or initiation of HF device therapy; (2) heart rate <60 bpm (except if cardiac resynchronization therapy in place); and (3) ongoing treatment with amiodarone at enrollment. Together, these criteria accounted for 53.3% of all exclusions. Patient characteristics by eligibility status are shown in Figure 2. Eligible patients were younger, had lower LVEF, and a higher prevalence of DM, AF, and advanced CKD than non-eligible patients. GDMT use was comparable between the two groups.

Conclusion

In a contemporary real-world cohort of patients with HFrEF, approximately 18.7% would be eligible for digitoxin according to the DIGIT-HF trial selection criteria.Consort diagram of the study populationFor image description, please refer to the figure legend and surrounding text.Patients characteristics by eligibilityFor image description, please refer to the figure legend and surrounding text.