Abstract 10213: Digoxin Use and Risk of Mortality in Hypertensive Patients With Atrial Fibrillation: The LIFE Study

Background: Digoxin (dig) is widely used for rate control of atrial fibrillation (AF). However, recent studies have reported conflicting results on the association of dig use in AF with mortality. Moreover, the relationship of dig use to mortality in hypertensive patients with AF has not been examined. Methods: Risk of all-cause mortality was examined in relation to in-treatment use of dig in 937 hypertensive patients in AF at baseline (n=134) or who developed AF during follow-up (n=803) with data on dig use at baseline and during treatment, randomly assigned to losartan- or atenolol-based treatment. Results: During 4.7±1.1 years follow-up, 167 patients died (17.8%) and 372 (39.7%) were on dig at some time. In univariate Cox analyses, in-treatment dig use, entered as a time-varying covariate, was associated with a 61% higher risk of death (95% CI 18-119%). After adjusting for other univariate predictors of death in this population, including age, diabetes, history of ischemic heart disease, stroke or heart failure, baseline Cornell product, QRS duration, heart rate, serum glucose, creatinine and HDL, and a propensity score for dig use entered as standard covariates, and for in-treatment heart rate, systolic pressure and Sokolow-Lyon voltage treated as time-varying covariates, dig use was no longer a significant predictor of mortality (HR 1.06, 95% CI 0.75-1.51, p=0.745). In parallel analyses excluding the 175 patients on dig at baseline, in-treatment dig use was no longer a univariate (HR 1.10, 95% CI 0.71-1.68) or multivariate (HR 0.85, 95% CI 0.54-1.34) predictor of death. Similarly, if the 45 patients with a history of heart failure were excluded, in-treatment dig use was of borderline significance in univariate analyses (HR 1.38, 95% CI 0.99-1.93) but was not a significant predictor of death in multivariate Cox analyses (HR 0.97, 95% CI 0.67-1.41). Conclusions: In hypertensive patients with existing or new AF, dig use is not associated with a significantly increased risk of all-cause mortality after adjusting for other independent predictors of death and for the factors associated with the propensity to use dig in this population. These findings suggest that factors other than dig use may account for the increased mortality found with dig use in some studies.