The authors note that there have been several observational studies published since the DIG study that have raised concerns about the safety of digoxin therapy for AF or CHF. They say their analysis provides further evidence for a harmful effect of digoxin on mortality; it is however subject to a number of potential limitations. The majority of the included studies were observational and although they adjusted for potential confounders, the possibility of residual confounding cannot be excluded. There was no access to individual patient data, and only a few studies reported data on digoxin dose or plasma levels.
The authors call for randomised controlled trials of dose-adjusted digoxin and recommend that it be used with great caution (with plasma level monitoring) until such has been completed, particularly when administered for rate control in AF.