Digoxin may increase mortality in patients with atrial fibrillation (AF) and congestive heart failure (CHF), according to the new a meta-analysis. Researchers combined 19 studies, which included more than 235,000 patients with AF and 91,000 patients with CHF. Based on the analysis of adjusted mortality results from all 19 studies, digoxin use was associated with an increased relative risk of all-cause mortality (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.07-1.38; P < 0.01). Among AF patients alone, digoxin compared to no glycosides was associated with a 29% increased mortality risk (HR 1.29, 95% CI, 1.06-1.22). The hazard ratio for CHF was 1.14 (1.14; 95% CI, 1.06-1.36, P < 0.01). Among the 19 studies, there was only one randomized controlled trial of digoxin in CHF patients that did not show either a benefit or risk of the drug, although there was a reduced risk of hospitalization for CHF. The mechanism for the increased risk is unknown, but it may be due to a narrow therapeutic window for digoxin, as well as the drug’s proarrhythmic effects. The authors conclude that digoxin therapy, especially without proper serum level control, is associated with an increased mortality risk in patients with AF and CHF, with a higher risk in AF. They further state “digoxin should be used with great caution (including monitoring plasma levels), particularly when administered for rate control and in AF.” (Published online Eur Heart J 4 May 2015; doi: http://dx.doi.org/10.1093/eurheartj/ehv143).