The safety of digoxin as a pharmacological treatment of atrial fibrillation.

Digoxin has traditionally been the drug of choice for ventricular rate control in patients with chronic atrial fibrillation (AF), with or without heart failure (HF) with systolic dysfunction. In patients with permanent AF, digoxin monotherapy is ineffective to control ventricular rate during exercise, but the combination of digoxin with a beta-blocker or a non-dihydropyridine calcium channel antagonist can control heart rate both at rest and during exercise. Only a few randomised, controlled studies have evaluated the adverse effects of digoxin in patients with AF in a systematic way and side effects requiring drug withdrawal have rarely been reported. When reported, the most frequent adverse effects were cardiac arrhythmias (ventricular arrhythmias, AV block of varying degrees and sinus pauses). This evidence suggested that, in contrast to other antiarrhythmic drugs, digoxin is a safe drug in patients with AF. However, this safety profile can be erroneous due to the short follow-up of the studies and patient selection. Because patients with HF have been excluded in most studies, the safety profile of digoxin in this population has not been directly addressed. Early recognition that an arrhythmia is related to digoxin intoxication as well as recognition of concomitant medications or medical conditions that may directly alter the pharmacokinetic profile of digoxin, or indirectly alter its cardiac effects by pharmacodynamic interactions remain essential for safe and effective use of digoxin in patients with AF.