Digoxin and Risk of Ventricular Tachyarrhythmia and Death in ICD Recipients

Area of Science:

• Cardiology
• Electrophysiology
• Pharmacology

Background:

• Digoxin use has been linked to adverse outcomes, including increased mortality.
• Limited data exist on digoxin's association with ventricular tachycardia/ventricular fibrillation (VT/VF) risk in heart failure patients with implantable cardioverter-defibrillators (ICDs).

Purpose of the Study:

• To assess the association between digoxin use and the risk of VT/VF in patients with heart failure with reduced ejection fraction and a primary prevention ICD.
• To evaluate the impact of digoxin on VT/VF, composite VT/VF or death, and all-cause mortality within landmark clinical trials.

Main Methods:

• Analysis of patients from 4 landmark Multicenter Automatic Defibrillator Implantation Trials (MADIT) with an ICD or cardiac resynchronization therapy-defibrillator.
• Propensity score quintile stratification and multivariable adjustment to compare digoxin versus no-digoxin therapy.
• Proportional hazards regression models incorporating adjustments for the competing risk of death for arrhythmia-specific endpoints.

Main Results:

• Digoxin use was associated with a statistically significant 48% increased risk of VT/VF (P < 0.001).
• Patients on digoxin showed a 42% increased risk of VT/VF or death (P < 0.001) and a 37% increased risk of all-cause mortality (P = 0.006).
• Digoxin use correlated with increased risk of appropriate ICD shocks (HR: 1.91) and a higher burden of VT/VF events (HR: 1.46).

Conclusions:

• Digoxin use is associated with an increased risk of ventricular tachyarrhythmia in heart failure patients with reduced ejection fraction and an ICD.
• The findings suggest a link between digoxin and increased mortality in this specific patient group.
• Caution is advised regarding digoxin use in heart failure patients with ICDs, particularly for primary prevention of sudden cardiac death.