Increased Mortality Among Patients Taking Digoxin: Analysis From the AFFIRM Study

Study Questions:

Does digoxin independently contribute to mortality in patients with atrial fibrillation (AF)?


This was a post-hoc analysis of the AFFIRM (Atrial Fibrillation Follow-Up Investigation of Rhythm Management) study, in which patients with AF were randomly assigned to a rate-control strategy (n = 2,027) or a rhythm-control strategy (n = 2,033). Mortality endpoints were compared in patients who did and did not receive digoxin during the study.


Overall, 69.4% of patients received digoxin during the study. The mortality rate during a mean follow-up of 3.5 years was 16.4%, with 49.7% of deaths being cardiovascular in nature. Among the patients who died, 56.3% were taking digoxin at the time of last follow-up. In a multivariate analysis that included multiple potential confounding variables, digoxin was independently associated with a 41% higher risk of all-cause mortality, a 35% higher risk of cardiovascular mortality, and a 61% higher risk of arrhythmic death. A significant association between digoxin use and all-cause mortality was found in patients with and without heart failure.


The authors concluded that digoxin is associated with a significantly heightened risk of death in patients with AF, regardless of heart failure status.


A large Swedish cohort study reported that digoxin was associated with a 42% higher risk of death in patients with AF without heart failure. Furthermore, a post-hoc analysis of the Valsartan Heart Failure Trial found that digoxin independently was associated with a 28% higher risk of death in patients with heart failure. The present study provides additional evidence that digoxin should be avoided for rate control in patients with AF, particularly since it is less effective than beta-blockers and calcium channel blockers.

Clinical Topics: Dyslipidemia, Heart Failure and Cardiomyopathies, Lipid Metabolism, Acute Heart Failure

Keywords: Risk, Multivariate Analysis, Follow-Up Studies, Digoxin, Fatty Acids, Valine, Tetrazoles, Calcium Channel Blockers, Heart Failure, Cardiotonic Agents

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