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Efficacy and Safety of Digitalis Glycosides in Heart Failure: A Meta-Analysis
Kevin Damman1, Dirk J van Veldhuisen1, Johann Bauersachs2
1University of Groningen, Department of Cardiology, University Medical Center Groningen, Groningen, the Netherlands.
Insights
Digitalis glycosides reduce worsening heart failure events in patients with heart failure with mildly reduced ejection fraction (HFmrEF) or reduced ejection fraction (HFrEF). This therapy may be beneficial for managing HFmrEF and HFrEF outcomes.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Heart failure with mildly reduced ejection fraction (HFmrEF) and heart failure with reduced ejection fraction (HFrEF) are significant cardiovascular conditions.
- Digitalis glycosides are a class of drugs sometimes used as additional therapy for heart failure.
Purpose of the Study:
- To assess the impact of digitalis glycosides on clinical outcomes in patients diagnosed with HFmrEF or HFrEF.
- To determine the efficacy of digitalis glycosides in preventing cardiovascular death and worsening heart failure events.
Main Methods:
- A systematic review and meta-analysis of placebo-controlled randomized clinical trials was conducted.
- Studies included over 1000 patients and were published in English, with data extracted and analyzed using a fixed-effects model.
Main Results:
- Digitalis glycosides significantly reduced the composite outcome of cardiovascular death or worsening heart failure (HR, 0.85; 95% CI, 0.80-0.90).
- The primary benefit was driven by a reduction in worsening heart failure events (HR, 0.75; 95% CI, 0.69-0.81).
- No significant difference was observed in all-cause death or cardiovascular death alone.
Conclusions:
- Digitalis glycosides are associated with a reduced risk of worsening heart failure events in patients with HFmrEF or HFrEF.
- These findings support the use of digitalis glycosides as an additional therapy to mitigate worsening heart failure events in these patient populations.
Importance:
Digitalis glycosides may be used as additional therapy in patients with heart failure with mildly reduced ejection fraction (HFmrEF) or HF with reduced EF (HFrEF).
Objective:
To assess the effect of digitalis glycosides on clinical outcomes in patients with HFmrEF or HFrEF.
Data Sources And Study Selection:
PubMed was searched from inception to March 1, 2026, using medical subject headings and keywords related to digitalis glycosides and HF. The review was restricted to placebo-controlled randomized clinical trials including more than 1000 patients and articles published in the English language.
Data Extraction And Synthesis:
Data were extracted by 2 reviewers who followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline. Risk of bias was assessed with the Cochrane Risk of Bias tool (version 2). A fixed-effects model was used to estimate the hazard ratios (HRs) with 95% CIs.
Main Outcomes And Measures:
The primary end point was the composite of time to cardiovascular death or first worsening HF event. Secondary outcomes included individual components of the composite outcome and time to all-cause death.
Results:
A total of 3 studies met the inclusion criteria and included 9013 patients with HFmrEF or HFrEF (weighted mean age, 64.5 [weighted SD, 11.2] years; 22% female and 78% male). The composite outcome of cardiovascular death or first worsening HF event occurred in 1852 of 4510 patients (41%) in the digitalis glycoside group vs 2037 of 4503 patients (45%) in the placebo group (HR, 0.85 [95% CI, 0.80-0.90]; P < .001). First worsening HF event occurred in 1183 (26%) patients in the digitalis glycoside group vs 1474 (33%) patients in the placebo group (HR, 0.75 [95% CI, 0.69-0.81]; P < .001). There were 1224 cardiovascular events in the digitalis glycoside group vs 1224 in the placebo group (27% of participants in each group; HR, 0.99 [95% CI, 0.92-1.07]; P = .81) and there were 1466 vs 1497, respectively, all-cause deaths (32% of participants vs 33%; HR, 0.97 [95% CI, 0.90-1.04]; P = .41). There was no statistically significant heterogeneity by trial, type of digitalis glycoside treatment, or extent of background HF therapy.
Conclusions And Relevance:
Treatment with digitalis glycosides was associated with a lower risk of the composite of cardiovascular death or first worsening HF event in patients with HFmrEF or HFrEF, mainly through a lower risk of worsening HF events. There was no statistically significant interaction with important study characteristics, including the extent of HF background therapy or type of digitalis glycosides treatment. These results suggest digitalis glycosides may be used as additional medical therapy to reduce worsening HF events in patients with HFmrEF or HFrEF.
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