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Are Digoxin’s Days as AF Treatment Numbered?

May 14, 2015

Digoxin might increase risk of death in patients with atrial fibrillation (AF) and congestive heart failure (CHF), according to the largest-ever study to assess the drug’s impact on all-cause mortality rates.

The review of 19 high-quality studies published over the last 2 decades included approximately 235,000 AF patients and more than 91,000 patients with CHF. The findings showed digoxin was associated with a 21% increase in risk of all-cause mortality. Among the roughly 117,000 patients with both conditions, the drug increased risk of death in patients with AF, but not in patients with CHF, which, said the researchers, suggested the drug does more harm when it’s used to manage heart rate issues.

Digoxin has a narrow therapeutic window that demands precise management and constant measurement of the drug’s serum levels in order to avoid interactions with other medications that can cause patient harm and potentially increase risk of death, noted the researchers. They referenced previous research that showed serum levels of 1.2 ng/ml or higher increased mortality risks, while levels below that threshold provided clinical benefit. The study also noted that digoxin has doubled rates of AF relapse following cardioversion and might also cause dangerous increases in heart rate. Risks of these potential adverse events are heightened by interactions with antiarrhythmic drugs, including amiodarone, quinidine, and dronedarone, said the study.

Clinical care guidelines support the use of digoxin to treat heart failure patients with impaired left-ventricular function and to regulate heart rhythm in AF patients, even though clinical research has yet to offer conclusive support for its use, said the study.

The drug has been used for decades in approximately 1 in 3 AF patients, according to Dr. Stefan Hohnloser, study co-author and a professor of cardiology at J. W. Goethe University in Frankfurt, Germany. But, he added, “My personal feeling is that the time of digoxin — particularly as a heart rate-controlling drug in AF — is over.”

“Our analysis, together with evidence from other studies, all point in the same direction — there is harm associated with the use of digoxin,” continued Dr. Hohnloser. “We need randomized controlled trials to examine the use of digoxin for both conditions and that test the drug versus a placebo or another active treatment.”

In the meantime, health-system pharmacists need to focus on the safe use of the drug by targeting patients who would benefit the most from the therapy. And if patients are treated with digoxin, careful monitoring, including measurements of plasma concentrations, is mandatory, said Dr. Hohnloser.

The study was published online in the European Heart Journal.


—Dan Cook



1. Vamos M, Erath JW, Hohnloser SH. Digoxin-associated mortality: a systematic review and meta-analysis of the literature. Eur Heart J. 2015 May 4. [Epub ahead of print]




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