Is foxglove effective in heart failure?
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.


CONCLUSIONS
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.
North West Heart Centre, University Hospital of South Manchester, Manchester, UK.
Parminder S
PS
Chaggar
North West Heart Centre, University Hospital of South Manchester, Manchester, UK.
Steven M
SM
Shaw
North West Heart Centre, University Hospital of South Manchester, Manchester, UK.
Simon G
SG
Williams
D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D002316:Cardiotonic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004070:Digitalis; D004077:Digoxin / Q000009:adverse effects / Q000627:therapeutic use*; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome
D000889:Anti-Arrhythmia Agents; D002316:Cardiotonic Agents; D004077:Digoxin
Arrhythmias; Digoxin; Heart failure; Renal dysfunction