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Published on: February 26, 2013
Digoxin use and risk of mortality in hypertensive patients with atrial fibrillation
Peter M Okin1, Darcy A Hille, Kristian Wachtell
1aGreenberg Division of Cardiology, Weill Cornell Medical College, New York bMerck Research Laboratories, West Point, Pennsylvania, USA cDepartment of Medicine, Glostrup University Hospital, Glostrup, Denmark dDepartment of Cardiology, University of Oslo, Ullevål Hospital, Oslo, Norway eResearch Unit, Department of Medicine, Skellefteå Hospital Institution of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden fDepartment of Medicine, Sahlgrenska University Hospital/Östra, Göteborg, Sweden.
Insights
In hypertensive patients with atrial fibrillation, digoxin use was not linked to increased mortality after accounting for other risk factors. This suggests other elements may explain higher death rates observed in some digoxin studies.
Area of Science:
- Cardiology
- Clinical Pharmacology
Background:
- Digoxin is a common treatment for atrial fibrillation rate control.
- Conflicting data exists on digoxin's association with mortality in atrial fibrillation patients.
- The impact of digoxin on mortality in hypertensive atrial fibrillation patients remains unclear.
Purpose of the Study:
- To investigate the association between digoxin use and all-cause mortality in hypertensive patients with atrial fibrillation.
- To determine if digoxin use is an independent predictor of mortality in this specific patient population.
Main Methods:
- Post-hoc analysis of the Losartan Intervention For Endpoint Reduction in hypertension (LIFE) trial substudy.
- Included 937 hypertensive patients with left ventricular hypertrophy and atrial fibrillation.
- Used Cox regression with time-varying covariates and propensity score adjustment.
Main Results:
- Univariate analysis showed digoxin use was associated with a 61% higher risk of death.
- After adjusting for multiple confounders and propensity scores, digoxin use was not a significant predictor of mortality (HR 1.04).
- The association between digoxin and mortality disappeared after comprehensive statistical adjustment.
Conclusions:
- Digoxin use is not significantly associated with increased all-cause mortality in hypertensive patients with atrial fibrillation and left ventricular hypertrophy.
- Adjustments for mortality predictors and digoxin propensity factors eliminated the observed association.
- Findings suggest that unmeasured factors, not digoxin itself, may contribute to increased mortality in some studies.
Background:
Digoxin is widely used for rate control of atrial fibrillation. However, recent studies have reported conflicting results on the association of digoxin with mortality when used in patients with atrial fibrillation. Moreover, the relationship of digoxin use to mortality in hypertensive patients with atrial fibrillation has not been examined.
Methods And Results:
All-cause mortality was examined in relation to in-treatment digoxin use in 937 hypertensive patients with ECG left ventricular hypertrophy in atrial fibrillation at baseline (n = 134) or who developed atrial fibrillation during follow-up (n = 803), randomly assigned to losartan or atenolol-based treatment, in post-hoc analysis of a substudy of the Losartan Intervention For Endpoint Reduction in hypertension (LIFE) trial. During 4.7 ± 1.1 years of mean follow-up, 167 patients died (17.8%) and 372 (39.7%) were treated with digoxin. In univariate Cox analyses, in-treatment digoxin use, entered as a time-varying covariate, was associated with a 61% higher risk of dying (hazard ratio 1.61, 95% confidence interval 1.18-2.19, P = 0.003). 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 high-density lipoprotein cholesterol, and a propensity score for digoxin use entered as standard covariates, and for in-treatment heart rate, pulse pressure, and Sokolow-Lyon voltage treated as time-varying covariates, digoxin use was no longer a significant predictor of mortality (hazard ratio 1.04, 95% confidence interval 0.73-1.48, P = 0.839).
Conclusion:
In hypertensive patients with ECG left ventricular hypertrophy with existing or new atrial fibrillation, digoxin 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 digoxin in this population. These findings suggest that factors other than digoxin use may account for the increased mortality found with digoxin use in some studies.
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