Meta-Analysis of Effects of Digoxin on Survival in Patients with Atrial Fibrillation or Heart Failure: An Update.

In 2015, 3 independent meta-analyses raised concerns about digoxin therapy being associated with an increased mortality risk in patients with atrial fibrillation (AF) and with heart failure (HF). Although several other studies have been published since then fostering these safety issues, the most recent 2016 European guidelines for AF still recommend this therapy as a class I indication. We performed an updated systematic review and random-effect meta-analysis on publications up to March 2018 reporting data on digoxin associated mortality in subjects with AF or HF. Based on the adjusted survival data of all identified 37 trials comprising a total of 825,061 patients, digoxin use was associated with an increased relative risk of all-cause mortality (hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.05 to 1.29, p <0.01). Treatment with digoxin was associated with an increased mortality risk in the subgroup of patients with AF (n = 627,620, HR 1.23, 95% CI, 1.17 to 1.30, p <0.01), and in the subgroup of patients with HF (n = 197,441, HR 1.11, 95% CI, 1.06 to 1.16, p<0.01). A sensitivity analysis of studies reporting data on new digoxin users (n = 41,687) demonstrated an even higher risk for all-cause mortality compared with patients not receiving cardiac glycosides (HR 1.47, 95% CI, 1.15 to 1.88, p <0.01). In conclusion, this updated meta-analysis confirms that digoxin use is associated with increased mortality in patients with AF or HF.