Digoxin for patients with atrial fibrillation and heart failure: paradise lost or not?
Key result
Digoxin use was associated with an increase in all-cause mortality among patients with atrial fibrillation (HR 1.41; 95% CI 1.19-1.67; P<0.001).
Why the study?
Does digoxin increase all-cause mortality in patients with atrial fibrillation with or without heart failure?
Population
4060 patients with atrial fibrillation and a high risk of stroke from the AFFIRM trial, including 26.5% with…
Comparison
Digoxin vs Patients not receiving digoxin
Design
Editorial
Follow-up
mean 3.5 years
Authors
Discussion
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Implication
This editorial cautions that while post hoc analyses suggest digoxin increases mortality in AF patients, these findings are limited by confounding and high target serum concentrations, suggesting low-dose digoxin may still have a role as a neurohormonal modulator in heart failure.
Structured PICO
Does digoxin increase all-cause mortality in patients with atrial fibrillation with or without heart failure?
P
Population
4,060 patients with atrial fibrillation and a high risk of stroke from the AFFIRM trial, followed for a mean of 3.5 years.
E
Exposure
Digoxin (used for rate or rhythm control, with target serum digoxin concentration ≥1.0 ng/mL encouraged in the protocol)
C
Comparator
Patients not receiving digoxin
O
Outcome
All-cause mortalityhard clinical
Main Result
Hazard Ratio: 1.41 (95% CI 1.19–1.67)
p-value: p=<0.001
This editorial cautions that while post hoc analyses suggest digoxin increases mortality in AF patients, these findings are limited by confounding and high target serum concentrations, suggesting low-dose digoxin may still have a role as a neurohormonal modulator in heart failure.
Limitations
- Post hoc analysis not performed by the original investigators
- Patients were not randomized to digoxin therapy
- Propensity-adjusted analyses may not have accounted for important clinical parameters like renal function or heart failure severity
- High target serum digoxin concentrations in the trial protocol may have caused toxicity
- Treatment with digoxin was not randomized
- Unclear if propensity adjustments adequately controlled for important clinical parameters like renal function and HF severity
- High target serum digoxin concentrations (≥1.0 ng/mL) may have led to unrecognized digoxin toxicity
Cite This Study
Veldhuisen et al. (2013) conducted an editorial in Atrial fibrillation (n=4,060). Digoxin vs. No digoxin was evaluated on All-cause mortality (HR 1.41, 95% CI 1.19-1.67, p=<0.001). Digoxin use was associated with an increase in all-cause mortality among patients with atrial fibrillation (HR 1.41; 95% CI 1.19-1.67; P<0.001).