LAUSR

Heart failure (HF) remains a large medical problem with an unacceptably high morbidity and mortality despite optimal medical and device treatment.1 Digoxin is the oldest drug in cardiovascular medicine, and in the most recent HF guidelines of the European Society of Cardiology (ESC) of 2016, it received a IIb-B recommendation,1 i.e. it may be considered in HF patients with reduced ejection fraction (HFrEF) who are in sinus rhythm, and still symptomatic despite treatment with an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) or an angiotensin-receptor neprilysin inhibitor (ARNI), a beta-blocker and a mineralocorticoid receptor antagonist (MRA), to reduce the risk of hospitalization. This IIb-B recommendation is much lower than the IA level digoxin still had in the 2001 American College of Cardiology/American Heart Association (ACC/AHA) guidelines,2 and along with this change, the use of digoxin has gradually declined from more than 60% in a large European study in the 1990s3 to less than 10% in a more recent trial in patients with HF and sinus rhythm (data from COMMANDER HF4). The use of digoxin has also declined in patients with atrial fibrillation (AF) (and HF), and in the 2016 ESC HF guidelines, digoxin is only recommended for the treatment of patients with HFrEF and AF to slow a rapid ventricular rate.1 Interestingly, not a single randomized clinical trial has ever been conducted in this AF population. The recommendation for digoxin is based on one large trial (Digitalis Investigation Group, DIG), published in 1997, that was conducted in almost 8000 patients in sinus rhythm.5 Patients in the DIG trial were on ACE inhibitors and diuretics, but not on beta-blockers, and the use of digoxin led to a 28% reduction in hospitalizations. Since its publication, a large number of subanalyses of the DIG trial have been conducted, which demonstrated that digoxin was more effective in more advanced HF,6 and in patients who had lower serum digoxin levels.7,8 In the present issue of the Journal, McMurray’s group from Glasgow report the results of another subanalysis of the DIG trial,