MP-453089-1 DIGOXIN AND RISK OF VENTRICULAR TACHYARRHYTHMIA AND DEATH IN ICD RECIPIENTS

Abstract

Digoxin continues to be used in patients with heart failure with reduced ejection fraction (HFrEF), especially among those with atrial fibrillation (AF) with difficult to control ventricular response. However, 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 implantable cardioverter defibrillator (ICD) recipients. We sought to assess whether digoxin use would be associated with increased risk of VT/VF in patients with HFrEF who were implanted with a primary prevention ICD in landmark clinical trials. Our study cohort consisted of patients with an ICD or cardiac resynchronization therapy-defibrillator (CRT-D) who were enrolled in the four landmark MADIT trials. Propensity score for digoxin at baseline was developed using a wide variety of baseline clinical measures with a logistic regression model stepwise variable selection approach. All potential variables which met a significance level <0.10 were included in the propensity score model. Additionally, a multivariate proportional hazards regression model was developed for the endpoint of VT/VF. This multivariate model was used along with propensity score quintile stratification for the endpoints of VT/VF, death and VT/VF/death. At baseline, 1155 of 4499 patients were on digoxin (26%). Propensity score variables are shown in Table 1. From statistical models using both multivariate adjustment and propensity score quintile stratification, patients prescribed digoxin exhibited a statistically significant 28% increased risk of VT/VF [HR 1.28 (1.10-1.50); p=0.002; Figure 1A], 38% increased risk of the composite of VT/VF or death [HR 1.38 (1.21-1.58); p<0.0001; Figure 1B]; and a 64% increased risk of death [HR 1.64; (1.32-2.04); p<0.0001]. Our findings suggest that digoxin use is associated with a significant increased risk of ventricular tachyarrhythmic events and death among ICD recipients. This adds to the growing evidence that digoxin use is associated with adverse outcomes in certain groups of patients and suggest a need for reconsideration on use of digoxin in HFrEF patients with an ICD.