Digoxin in Atrial Fibrillation: The Beat Goes on


Despite the most recent meta-analysis published this week in the British Medical Journal, digoxin use in atrial fibrillation remains limited.

Although the TREAT-AF study suggested that digoxin has a negative impact on patient survival, the drug's pursuit of a more prominent role in atrial fibrillation treatment continues.

A new meta-analysis published in BMJ sought to "clarify the impact of digoxin on death and clinical outcomes across all observational and randomized controlled trials."1

Digoxin’s role in heart failure is supported by randomized trials and large observational cohorts, but data from similarly designed trials on the drug's role in atrial fibrillation are limited, particularly for outcomes such as mortality, hospital admission, and cardiovascular complications.

By analyzing all available observational and experimental studies, the authors believed that stronger recommendations for digoxin use in atrial fibrillation could be made.

Without question, the available data for their analysis largely stemmed from observational studies, rather than randomized trials. This was particularly true for the treatment of atrial fibrillation, where the authors found no suitable studies for their meta-analysis.

Therefore, reviewing the available data yielded the same result: digoxin use in heart failure and atrial fibrillation is associated with increased mortality.

As the authors noted several times throughout their manuscript, observational trials are subject to significant confounders, biases, and high heterogeneity. But when the data were controlled for such factors and propensity matched, the results remained the same.

It was only when the authors selected exclusively randomized trials of patients with heart failure, not atrial fibrillation, that digoxin caused no change in mortality, but may have reduced the risk of cardiovascular-related hospitalization.

The tone of the manuscript was overtly optimistic regarding digoxin. For instance, the authors argued that beta-blockers used in atrial fibrillation do not decrease mortality or have any effect on morbidity.

"In this context, clinicians have only a single other choice of rate control treatment—namely, digoxin—as calcium channel blockers can have negatively inotropic effects in failing heart," they wrote.

This heavy-handed statement may take some clinicians by surprise, but most would not change their practice, despite the authors' arguments.

Digoxin has its place in both heart failure and atrial fibrillation treatment, and this meta-analysis should not change that.


1. Ziff Oliver J, Lane Deirdre A, Samra Monica, Griffith Michael, Kirchhof Paulus, Lip Gregory Y H et al. Safety and efficacy of digoxin: systematic review and meta-analysis of observational and controlled trial data. BMJ. 2015;351:h4451.

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