Digitalis glycosides reduce worsening HF events in patients with HFrEF/HFmrEF
ESC Heart Failure 2026 – In a study-level meta-analysis, digitalis glycosides reduced the risk of the primary composite outcome of CV death or first worsening HF event compared with placebo in patients with HFrEF/HFmrEF.
This summary is based on the presentation of Kevin Damman, MD, PhD (Groningen, The Netherlands) at the ESC Heart Failure Congress 2026 - Efficacy and safety of digitalis glycosides in HF: a study level meta-analysis. Data from DIG, DIGIT-HF and DECISION.
Introduction and methods
Digitalis glycosides such as digoxin and digitoxin are one of the oldest drugs used in heart failure (HF). However, these drugs are no longer considered first line HF treatments since the introduction of new foundational therapies. Recently, new data have become available about the effects of digitalis glycosides in HF patients receiving contemporary background therapy.
The aim of this meta-analysis was to investigate the effect of digitalis glycosides in patients with HFrEF/HFmrEF.
In this study-level meta-analysis, data were pooled from 3 placebo-controlled RCTs comparing the effects of digitalis glycosides versus placebo in a total of 9013 patients with HFrEF/HFmrEF: DIG, DIGIT-HF and DECISION trials. The DIG trial (n=6800) evaluated the effects digoxin, DIGIT-HF trial (n=1212) evaluated the effects of low-dose digitoxin, whereas the DECISION trial (n=1001) evaluated the effects of low-dose digoxin. Patients in the DIGIT-HF and DECISION trials received contemporary HF background therapy. The prespecified primary analysis used fixed effect modelling to pool study level hazard ratios.
The primary composite outcome was CV death or first worsening HF event.
Main results
- Digitalis glycosides reduced the risk of the primary composite outcome of CV death or first worsening HF event compared with placebo (HR: 0.85: 95%CI: 0.80-0.90; P<0.001).
- There was no heterogeneity across the studies.
- Digitalis glycosides reduced the risk of first worsening HF event compared with placebo (HR: 0.75; 95%CI: 0.75-0.81; P<0.001).
- There was no effect on CV death (HR: 0.99; 95%CI: 0.92-1.07; P=0.81) or all-cause death (HR: 0.97; 95%CI: 0.90-1.04; P=0.41).
- In sensitivity analysis, the effects on the primary outcome were consistent across type of digitalis glycoside (digoxin vs. digitoxin) and treatment era (DIG vs. DIGIT-HF/DECISION).
Conclusion
In this study-level meta-analysis, digitalis glycosides reduced the risk of the primary composite outcome of CV death or first worsening HF event by 15% in patients with HFrEF/HFmrEF compared with placebo. The benefit was mainly driven by first worsening HF events. “These data support the use of low dose digitalis glycosides as additional medical therapy in HF patients with mildly reduced or reduced ejection fraction,” said Kevin Damman.
- Our reporting is based on the information provided at the ESC Heart Failure Congress 2026 -