Digoxin Carries More Than 200 Years of Controversy, Especially in Atrial Fibrillation

Approximately 6.5 million Americans are prescribed digoxin, a cardiac glycoside with a long, fascinating history. Given the drug’s prevalence, any potential problems related to its use are generally propelled into the public health arena.

A new editorial and review published in the September/October 2014 issue of the American Journal of Therapeutics discussed several historical and recent concerns associated with digoxin. Among the authors’ findings were the following key points:

• The foxglove-derived medication has been trailed by controversies since its original discovery in 1785.
• Typically, digoxin’s low therapeutic-to-toxic ratio of approximately 2 to 1 is at the center of every related controversy.
• Various digoxin preparations, such as stropanthis and ouabain, have been withdrawn, mainly due to their unpredictable differences.
• Much of digoxin’s toxicity has been attributed to its combined use with quinidine, a practice that is now discouraged and avoided.
• An analysis of 122,465 veterans determined that digoxin use was associated with an increased risk of death in patients with newly diagnosed atrial fibrillation (AF).
• The randomized AFFIRM trial found that patients treated with digoxin had an elevated risk of death, though a similar review of the same data that used different analytical techniques found no association between digoxin and increased mortality.
• Heart failure (HF), ischemia, and myocardial infraction, either alone or in combination, can lower the therapeutic-to-toxic ratio of digoxin, meaning the drug not only increases mortality, but also confounds study results.
• Most physicians prescribe digoxin only for rate control in HF patients, as evidence indicated the drug improves rate control and reduces HF-related rehospitalization in this population.
• Using alternative therapies seems reasonable and rational, but their effect on mortality is still unclear.
• Controlled, perspective, and randomized trials that evaluate digoxin’s safety and therapeutic benefit in AF are sorely needed.