Can Cardiac Glycosides (Digoxin/Digitoxin) Return to Heart Failure Management?
Can Cardiac Glycosides (Digoxin/Digitoxin) Return to Heart Failure Management?
Source: Medscape Medical News | June 24, 2025
Key Points Summary:
1. Historical Context:
• Digoxin and digitoxin, derived from foxglove, have been used for centuries in cardiology.
• Based on the 1997 DIG trial, digoxin reduced HF hospitalizations, but had no effect on all-cause mortality.
• As modern therapies emerged, digoxin’s guideline status was downgraded from Class I to Class IIb.
. Key findings from the DIGIT-HF and DECISION trials—both re-evaluating the role of cardiac glycosides in HFrEF—are expected later this year, and will be essential in determining whether these agents merit renewed guideline support beyond limited use in patients with HFrEF and atrial fibrillation.
2. Modern Trials Exploring Revival:
DIGIT-HF Trial:
• Design: 1212 HFrEF patients receiving digitoxin or placebo + contemporary GDMT “Fantastic Four.
• Goal: Assess if low serum levels of digitoxin improve outcomes and are safe.
• Key Context:
• 40% on ARNI, 70% on MRA.
• 64% had ICDs; 25% had CRT.
• Preferred over digoxin for patients with renal impairment (digitoxin = hepatic clearance).
• Special interest in AF + HFrEF patients needing rate control when β-blockers are insufficient.
DECISION Trial:
• Over 1000 symptomatic HF patients (LVEF <50%).
• Uses low-dose digoxin (target 0.5–0.9 ng/mL), avoiding higher levels linked to mortality in the DIG trial.
• Enrolled more women to improve representation and analysis.
3. Why Revisit Cardiac Glycosides?
• Many HFrEF patients remain symptomatic despite full use of the “Fantastic Four”:
1. ARNI
2. Beta-blockers
3. MRAs
4. SGLT2 inhibitors
• In patients with AF and HFrEF, glycosides may still be valuable for rate control.
4. Guideline Perspective – AHA 2022 (U.S.):
• Cardiac glycosides can be considered in:
• Symptomatic HFrEF patients despite optimal GDMT.
• Patients who cannot tolerate full GDMT.
• Goal: reduce HF hospitalizations, not mortality.
Ongoing Questions & Caution:
• DIGIT-HF is stratified by AF status and may offer insight into digoxin’s role in AF + HFrEF.
• However, not all patients in the trial were receiving the complete GDMT at baseline.
• Experts caution that additional trials are needed before glycosides can regain strong guideline support.
