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Digoxin and Risk of Ventricular Tachyarrhythmia and Death in ICD Recipients
Amole Ojo1, Scott McNitt1, Bronislava Polonsky1
1Clinical Cardiovascular Research Center, University of Rochester Medical Center, Rochester, New York, USA.
Insights
Digoxin use in heart failure patients with an implantable cardioverter-defibrillator (ICD) is linked to a significantly higher risk of ventricular tachycardia/ventricular fibrillation (VT/VF) and all-cause mortality. This study highlights potential adverse outcomes associated with digoxin in this patient population.
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.
Background:
Some studies have shown digoxin use to be associated with adverse outcomes, including increased mortality. There are limited data on whether digoxin use is associated with increased risk of ventricular tachycardia/ventricular fibrillation (VT/VF) in heart failure patients with an implantable cardioverter-defibrillator (ICD).
Objectives:
This study sought to assess whether digoxin use is associated with increased risk of VT/VF in patients with heart failure with reduced ejection fraction with a primary prevention ICD in landmark clinical trials.
Methods:
The study cohort consisted of patients with an ICD or cardiac resynchronization therapy-defibrillator who were enrolled in 4 landmark MADIT trials (Multicenter Automatic Defibrillator Implantation Trials). We employed propensity score quintile stratification for treatment with digoxin as well as additional multivariable adjustment to assess the risk of digoxin vs no-digoxin therapy for the endpoints of first and recurrent VT/VF and all-cause mortality. The proportional hazards regression models for arrhythmia-specific endpoints incorporated adjustments for the competing risk of death.
Results:
At baseline, 1,155 of 4,499 patients were on digoxin (26%). After propensity score quintile stratification, patients prescribed digoxin were shown to exhibit a statistically significant 48% increased risk of VT/VF (P < 0.001), 42% increased risk of the composite of VT/VF or death (P < 0.001), and a 37% increased risk of all-cause mortality (P = 0.006). Digoxin use was also associated with increased risk of appropriate ICD shocks (HR: 1.91; P < 0.001) and with increased burden of VT/VF events (HR: 1.46; P = 0.001).
Conclusions:
Our findings suggests that digoxin use is associated with ventricular tachyarrhythmia and death in heart failure with reduced ejection fraction patients with an ICD.
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