Digitalis Glycosides May Reduce Worsening HF Events in HFmrEF and HFrEF: Study
Netherlands: A new meta-analysis published in JAMA reported that treatment with digitalis glycosides was associated with a lower risk of the combined outcome of cardiovascular death or first worsening heart failure event in patients with heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with reduced ejection fraction (HFrEF).
The observed benefit was mainly attributed to a reduction in worsening heart failure episodes. Researchers also noted that the benefit remained consistent, irrespective of background heart failure therapy or the specific digitalis glycoside used, indicating that these agents could serve as supportive therapy for slowing the progression of heart failure.
The study was conducted by Kevin Damman from the University of Groningen, Department of Cardiology, University Medical Center Groningen, the Netherlands, along with colleagues.
Digitalis glycosides, such as digoxin and digitoxin, have long been used in the treatment of heart failure, but their clinical benefit in the modern treatment era remains uncertain. To evaluate their efficacy and safety in patients with HFmrEF or HFrEF, researchers conducted a meta-analysis of placebo-controlled randomized clinical trials.
The investigators searched PubMed through March 1, 2026, and included English-language trials enrolling more than 1000 participants. Data extraction and quality assessment were independently performed by two reviewers following PRISMA guidelines and the Cochrane Risk of Bias tool version 2.
A total of three large trials involving 9013 patients were included in the analysis. The weighted mean age was 64.5 years, and 22% of participants were women. The primary outcome was cardiovascular death or first worsening heart failure event, while secondary outcomes included cardiovascular events and all-cause mortality.
The following were the key findings of the study:
- The composite endpoint of cardiovascular death or first worsening heart failure event occurred in 41% of patients receiving digitalis glycosides compared with 45% in the placebo group.
- Treatment with digitalis glycosides was associated with a 15% lower risk of the primary composite outcome (HR 0.85).
- First worsening heart failure events occurred in 26% of patients treated with digitalis glycosides versus 33% in the placebo group.
- Digitalis glycoside therapy reduced the risk of worsening heart failure events by 25% (HR 0.75).
- Cardiovascular death rates were similar between the digitalis glycoside and placebo groups, with 1224 events reported in each arm.
- No significant difference in all-cause mortality was observed between patients receiving digitalis glycosides and those receiving a placebo.
- The benefits of treatment remained consistent regardless of trial characteristics, type of digitalis glycoside used, or the extent of background heart failure therapy.
The authors concluded that digitalis glycosides may offer additional therapeutic value in reducing worsening heart failure events among patients with HFmrEF or HFrEF, although they do not appear to improve survival outcomes.
Reference:
Damman K, van Veldhuisen DJ, Bauersachs J, et al. Efficacy and Safety of Digitalis Glycosides in Heart Failure: A Meta-Analysis. JAMA. Published online May 10, 2026. doi:10.1001/jama.2026.7886
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