Digoxin Use and Subsequent Clinical Outcomes in Patients With Atrial Fibrillation With or Without Heart Failure in the ENGAGE AF‐TIMI 48 Trial
Key result
Baseline digoxin use in patients with atrial fibrillation without heart failure was significantly associated with an increased risk of sudden cardiac death (HR 1.51).
Why the study?
Does digoxin use increase the risk of sudden cardiac death and mortality in patients with atrial fibrillation with or without heart failure?
Population
21,105 patients with atrial fibrillation with or without heart failure enrolled in the ENGAGE AF-TIMI 48 trial
Comparison
Digoxin use at baseline vs No digoxin use at baseline
Design
Cohort
Follow-up
median 2.8 years
Authors
Discussion
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Implication
Digoxin may warrant caution in AF; leaves open whether RCTs can confirm mortality signals after HF adjustment.
Key Points
- This research aims to examine the clinical outcomes associated with digoxin use in patients with atrial fibrillation, focusing on those with and without heart failure.
- Analyzed clinical outcomes from ENGAGE AF‐TIMI 48 trial with a median follow-up of 2.8 years.
- Evaluated 21,105 patients, with a subgroup of 6,327 (30%) using digoxin at baseline.
- Calculated hazard ratios for sudden cardiac death across different patient groups, including propensity matching.
- In patients without heart failure, digoxin use was associated with sudden cardiac death (adjusted HR 1.51; 95% CI 1.10–2.08).
- In patients with heart failure, digoxin use was linked to increased all-cause death, cardiovascular death, and sudden cardiac death (P < 0.01 for each).
- No association was found between digoxin use and noncardiovascular death, stroke/systemic embolism, or myocardial infarction.
Study Design
Type
Observational (n=21,105)
Multicenter
Yes
Structured PICO
Does digoxin use increase the risk of sudden cardiac death and mortality in patients with atrial fibrillation with or without heart failure?
P
Population
21,105 patients aged 21 years and older with atrial fibrillation and a CHADS2 score ≥2, with or without heart failure, followed for a median of 2.8 years.
E
Exposure
Digoxin use at baseline
C
Comparator
No digoxin use at baseline
O
Outcome
Sudden cardiac deathhard clinical
Main Result
Hazard Ratio: 1.51 (95% CI 1.1–2.08)
Absolute Event Rate: 1.2% vs 0.7%
p-value: p=0.01
Digoxin use in patients with atrial fibrillation is associated with an increased risk of sudden cardiac death and other mortality outcomes, regardless of the presence of heart failure.
Limitations
- Observational post hoc analysis subject to residual confounding
- Dose and drug concentrations of digoxin were not available
- Digoxin use was primarily considered at baseline
- Lack of documentation of arrhythmia, family history of SCD, and genetic tests for SCD events
- Results may not be generalized to low-risk patients with AF
- Residual confounding cannot be excluded
Cite This Study
Eisen et al. (2017) conducted an observational in Atrial Fibrillation (n=21,105). Digoxin vs. No digoxin was evaluated on Sudden cardiac death in patients without heart failure (HR 1.51, 95% CI 1.10-2.08, p=0.01). Baseline digoxin use in patients with atrial fibrillation without heart failure was significantly associated with an increased risk of sudden cardiac death (HR 1.51).