Meta-analysis of digoxin use and risk of mortality in patients with atrial fibrillation

There is an ongoing debate on the safety of digoxin use in patients with atrial fibrillation (AF). To address this issue, the investigators assembled a synthesis of the available evidence on the relation between digoxin and all-cause mortality in patients with AF. PubMed and the Embase database were systematically searched to identify all eligible studies examining the association between digoxin use and the mortality risk in AF. Overall hazard ratios and 95% confidence intervals were calculated using the random-effects model. Eleven observational studies were identified that met the inclusion criteria, 5 of which additionally used propensity score matching for statistical adjustment. In total, 318,191 patients were followed up for a mean of 2.8 years. Overall, digoxin use was associated with a 21% increased risk for mortality (hazard ratio 1.21, 95% confidence interval 1.12 to 1.30). Sensitivity analyses found the results to be robust. In the propensity score-matched AF patients, digoxin use was associated with a 17% greater risk for mortality (hazard ratio 1.17, 95% confidence interval 1.13 to 1.22). When the AF cohort was grouped into patients with and without heart failure, the use of digoxin was associated with an increase in mortality in patients with and those without heart failure, and no significant heterogeneity was seen between the groups (p >0.10). In conclusion, the results suggest that digoxin use was associated with a greater risk for mortality in patients with AF, regardless of concomitant heart failure. A well-powered randomized trial is necessary to reveal the true effect of digoxin.