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Is foxglove effective in heart failure?
Parminder S Chaggar1, Steven M Shaw1, Simon G Williams1
1North West Heart Centre, University Hospital of South Manchester, Manchester, UK.
Insights
Digoxin, a long-standing heart failure (HF) treatment, lacks definitive randomized evidence for efficacy as add-on therapy. Current data are conflicting, raising questions about its safety and optimal dosage in HF patients.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Digoxin is an established heart failure (HF) treatment, historically reducing HF admissions in patients with preserved ejection fraction.
- Current guidelines suggest digoxin for symptomatic HF despite optimal therapies, based on older trial data.
- Digoxin's use predates modern mortality-reducing HF treatments, necessitating a review of its efficacy and safety.
Purpose of the Study:
- To review historical and contemporary data on digoxin's efficacy and safety in heart failure (HF).
- To assess the current evidence base for digoxin as an add-on therapy in HF management.
Main Methods:
- Conducted multiple PubMed searches using terms like "digoxin," "heart failure," "efficacy," and "safety."
- Included randomized controlled trials and observational studies, excluding irrelevant or non-English articles.
- Manually searched reference lists of relevant articles for additional studies.
Main Results:
- Retrieved three randomized controlled trials and three large observational reports on digoxin in HF with sinus rhythm.
- Reviewed additional studies involving patients with HF and atrial fibrillation.
- Identified a lack of definitive randomized trials comparing digoxin with modern HF therapies.
Conclusions:
- Definitive randomized evidence for digoxin's efficacy as add-on HF therapy is lacking.
- Unanswered questions persist regarding optimal digoxin dosage and potential harm in some HF patients.
- Conflicting findings from observational studies highlight the need for further investigation into digoxin's role in HF.
Background:
Digoxin is the oldest known treatment for heart failure (HF) and has been demonstrated to reduce admissions for worsening heart failure in a large randomized trial recruiting patients in sinus rhythm with heart failure and ejection fraction <45%. This study forms the basis for current international guidelines recommending that digoxin should be considered in patients with symptomatic HF despite optimal doses of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β-blockers, and mineralocorticoid receptor antagonists in addition to device therapy, if indicated. However, digoxin predates mortality reducing HF therapies, and this article reviews the historical and recent data.
Methods:
Multiple PubMed searches were performed including, but not limited to, the search terms "digoxin," "heart failure," "efficacy," "treatment," "side-effects," "morbidity," "mortality," and "arrythmia." Articles were excluded if not relevant, not in English or without abstract. Reference lists of relevant articles were manually searched for further references. Due to the large number of articles retrieved, a selection was reviewed based on the authors' best judgement.
Results:
Three randomized controlled trials and three large contemporary observational reports of digoxin therapy in heart failure and sinus rhythm were retrieved. Other studies were noted that included patients with heart failure and atrial fibrillation, which were also reviewed.
Conclusion:
Definitive randomized evidence of digoxin efficacy as add-on therapy in HF is lacking because most landmark trials of modern HF disease modifying agents postdate the randomized studies of digoxin. Furthermore, questions remain regarding the optimum dose of digoxin and there are signals that digoxin may be harmful in some patients with HF. All contemporary data for digoxin in HF are derived from observational studies and the findings are conflicting. Despite two centuries of experience using cardiac glycosides to treat HF, fundamental questions regarding the efficacy and safety of digoxin in HF remain unanswered.
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