Digoxin for patients with atrial fibrillation and heart failure: paradise lost or not?

This editorial refers to ‘Increased mortality among patients taking digoxin—analysis from the AFFIRM study’, by M.G. Whitbeck et al. , doi:10.1093/eurheartj/ehs348 Digoxin is one of the oldest drugs in cardiovascular medicine, and it was traditionally used in patients with atrial fibrillation (AF) and heart failure (HF).1 In the last 20 years, the use of this drug has markedly declined, and in the most recent 2012 European Society of Cardiology (ESC) HF Guidelines,2 it is stated that for patients with HF and a left ventricular ejection fraction (LVEF) ≤40%, who are in sinus rhythm ‘digoxin may be used’. This recommendation is based on the Digitalis Investigation Group (DIG) trial,3 in which the effect of digoxin on outcome was examined in 6800 patients with HF. For HF patients with AF, other drugs (in particular beta-blockers) should be preferred,2 since they provide better rate control. In the 2010 ESC AF Guidelines,4 it is stated that digoxin is effective for long-term rate control at rest, but not during exercise. Prospective, randomized, placebo-controlled outcome studies examining the effect of digoxin in patients with AF (with or without HF) are not available. In the past, it was assumed that the beneficial effect of digoxin in HF was due to its (positive) inotropic properties, which were more pronounced at higher doses of the drug.1,5 However, a large number of studies in patients with HF has shown that positive inotropic drugs lead to an unfavourable effect on outcome, and these drugs are now contraindicated in patients with (chronic) HF. In contrast to this inotropic effect, digoxin also exerts potentially favourable autonomic- or neurohormonal-inhibiting properties,6,7 which primarily occur at lower serum digoxin concentrations (SDCs).1,5–7 This has been increasingly recognized in the last 25 years, …