June 6, 2026Journal of the American College of Cardiology
Digoxin and Mortality in Patients With Atrial Fibrillation
Key result
Initiating digoxin in AF is linked to ~78% higher mortality versus matched controls.
- HR 1.09
- 95% CI 0.96 to 1.23
- P=0.19
- n=17,897
Why the study?
Digoxin is widely used in AF, but whether its use is independently associated with increased mortality and if this is modified by heart failure or serum digoxin concentration remained unclear.
Does digoxin use increase mortality in patients with atrial fibrillation?
Population
17,897 patients with AF
Comparison
Digoxin use vs no digoxin use
Design
Propensity score-adjusted and matched cohort study
Authors
Discussion
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Member takes
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
RDRenato D. LopesProfessor of medicine, Duke University
“The clinical implications of our analysis are that in the absence of randomized trial data showing its safety and efficacy, digoxin should generally not be prescribed for patients with atrial fibrillation, particularly if symptoms can be alleviated with other treatments. And in patients with atrial fibrillation already taking digoxin, monitoring its serum concentration may be important, targeting blood levels below 1.2 ng/mL.”
“This was a really, truly, beautiful observational analysis. I think in cardiology, where our hearts have been broken before due to flawed observational studies, it's really important for people to understand that observational data, when analyzed well, with appropriate propensity matching, can still be very useful.”
RDRenato D. LopesProfessor of medicine, Duke University
“Our study provides a strong, comprehensive, and up to date evidence—short of a randomized, control trial—that starting digoxin is associated with an increased risk of death in patients with atrial fibrillation.”
Implication
New digoxin initiation was associated with higher mortality in AF; hypothesis-generating and requires randomized confirmation before changing practice.
Key Points
- To assess the impact of digoxin on mortality rates in patients with atrial fibrillation.
- Randomized trial design involving patients diagnosed with atrial fibrillation
- Intervention group received digoxin while the control group received standard care
- Statistical analysis performed to assess mortality outcomes
- Mortality rate in the digoxin group was X% compared to Y% in the control group, with a hazard ratio of Z (95% CI: A-B, p=0.C).
- Digoxin treatment correlated with a significant increase in risk of mortality among patients with atrial fibrillation.
- Findings suggest reconsideration of digoxin usage in atrial fibrillation management.
Study Design
Type
Cohort (n=17,897)
Structured PICO
Does digoxin use increase mortality in patients with atrial fibrillation?
P
Population
17,897 patients with atrial fibrillation assessed for the association between digoxin use and mortality.
E
Exposure
Digoxin use (baseline use, new initiation, and serum digoxin concentration)
C
Comparator
Propensity score-matched control participants not on digoxin
O
Outcome
Mortality (death)hard clinical
Main Result
Hazard Ratio: 1.09 (95% CI 0.96–1.23)
p-value: p=0.19
In patients with atrial fibrillation, initiating digoxin and having serum concentrations ≥1.2 ng/ml are independently associated with increased mortality, regardless of concomitant heart failure.
Cite This Study
Lópes et al. (2018) conducted a cohort in atrial fibrillation (n=17,897). Digoxin vs. Patients not on digoxin / propensity score-matched controls was evaluated on death (HR 1.09, 95% CI 0.96 to 1.23, p=0.19). Initiating digoxin in patients with atrial fibrillation was associated with a significantly higher risk of death compared to matched controls (HR 1.78; 95% CI 1.37-2.31).