Digoxin Again Linked to Death Risk in Atrial Fibrillation Patients

The largest and most recent analysis of digoxin has reaffirmed the drug’s association with a heightened risk of early death in patients with atrial fibrillation (AF) or congestive heart failure (CHF).

Published May 5, 2015, in the European Heart Journal, the study reviewed and analyzed 19 previous trials that examined the effect of digoxin on all-cause death in patients with AF or CHF. All of the studies were published between 1993 and 2014, and they enrolled a combined 235,047 AF patients and 91,379 CHF patients.

The research team found patients treated with digoxin had an overall 21% increased risk of all-cause death compared with those who did not receive the drug. Digoxin had a particularly notable effect on AF patients, as its use in this population was associated with a 29% increased risk of all-cause death. In CHF patients, digoxin use was linked to a 14% increase in mortality risk.

“Our analysis, together with evidence from other studies, all point in the same direction: there is harm associated with the use of digoxin,” said lead author Stefan Hohnloser, a cardiology professor at J.W. Goethe University in Frankfurt, Germany, in a press release.

The drug’s effect on the heart's rhythm and pumping ability may be partially responsible for triggering the mechanisms that lead to death, the study authors explained. These effects may be exacerbated by interactions with other drugs, such as dronedarone.

The authors acknowledged a need for more randomized, controlled studies on digoxin. Until such time, “digoxin should be used with great caution (including monitoring plasma levels), particularly when administered for rate control in AF,” they wrote.

An extract of the foxglove plant (digitalis), digoxin has sparked a number of concerns since it was first discovered in 1785. Much of the controversy surrounding the drug’s use has centered on its alarmingly low 2-to-1 therapeutic-to-toxic ratio, according to a review published in the September/October 2014 issue of the American Journal of Therapeutics.

Another recent study published in the Journal of the American College of Cardiology found newly diagnosed AF patients treated with digoxin were 1.2 times more likely to die early than those who received alternative AF treatments. In response to these findings, Craig Cocchio, PharmD, BCPS, noted the data only indicated an association, not causation, and emphasized randomized, controlled studies are needed to conclusively determine the risks.