Renato D Lopes1, Roberto Rordorf2, Gaetano M De Ferrari2, Sergio Leonardi2, Laine Thomas3, Daniel M Wojdyla3, Peter Ridefelt4, John H Lawrence5, Raffaele De Caterina6, Dragos Vinereanu7, Michael Hanna6, Greg Flaker8, Sana M Al-Khatib3, Stefan H Hohnloser9, John H Alexander3, Christopher B Granger3, Lars Wallentin10. 1. Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina. Electronic address: renato.lopes@duke.edu. 2. Coronary Care Unit and Laboratory of Clinical and Experimental Cardiology-Fondazione IRCCS Policlinico San Matteo, and Department of Molecular Medicine, University of Pavia, Pavia, Italy. 3. Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina. 4. Department of Medical Sciences, Uppsala University, Uppsala, Sweden. 5. Bristol-Myers Squibb, Princeton, New Jersey. 6. Institute of Cardiology, G.d'Annunzio University, Chieti, Italy. 7. University of Medicine and Pharmacy Carol Davila, University and Emergency Hospital, Bucharest, Romania. 8. University of Missouri, Columbia, Missouri. 9. J.W. Goethe University, Frankfurt, Germany. 10. Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Uppsala Clinical Research Center, Uppsala, Sweden.
Abstract
BACKGROUND:Digoxin is widely used in patients with atrial fibrillation (AF). OBJECTIVES: The goal of this paper was to explore whether digoxin use was independently associated with increased mortality in patients with AF and if the association was modified by heart failure and/or serum digoxin concentration. METHODS: The association between digoxin use and mortality was assessed in 17,897 patients by using a propensity score-adjusted analysis and in new digoxin users during the trial versus propensity score-matched control participants. The authors investigated the independent association between serum digoxin concentration and mortality after multivariable adjustment. RESULTS: At baseline, 5,824 (32.5%) patients were receiving digoxin. Baseline digoxin use was not associated with an increased risk of death (adjusted hazard ratio [HR]: 1.09; 95% confidence interval [CI]: 0.96 to 1.23; p = 0.19). However, patients with a serum digoxin concentration ≥1.2 ng/ml had a 56% increased hazard of mortality (adjusted HR: 1.56; 95% CI: 1.20 to 2.04) compared with those not on digoxin. When analyzed as a continuous variable, serum digoxin concentration was associated with a 19% higher adjusted hazard of death for each 0.5-ng/ml increase (p = 0.0010); these results were similar for patients with and without heart failure. Compared with propensity score-matched control participants, the risk of death (adjusted HR: 1.78; 95% CI: 1.37 to 2.31) and sudden death (adjusted HR: 2.14; 95% CI: 1.11 to 4.12) was significantly higher in new digoxin users. CONCLUSIONS: In patients with AF taking digoxin, the risk of death was independently related to serum digoxin concentration and was highest in patients with concentrations ≥1.2 ng/ml. Initiating digoxin was independently associated with higher mortality in patients with AF, regardless of heart failure.
RCT Entities:
BACKGROUND:Digoxin is widely used in patients with atrial fibrillation (AF). OBJECTIVES: The goal of this paper was to explore whether digoxin use was independently associated with increased mortality in patients with AF and if the association was modified by heart failure and/or serum digoxin concentration. METHODS: The association between digoxin use and mortality was assessed in 17,897 patients by using a propensity score-adjusted analysis and in new digoxin users during the trial versus propensity score-matched control participants. The authors investigated the independent association between serum digoxin concentration and mortality after multivariable adjustment. RESULTS: At baseline, 5,824 (32.5%) patients were receiving digoxin. Baseline digoxin use was not associated with an increased risk of death (adjusted hazard ratio [HR]: 1.09; 95% confidence interval [CI]: 0.96 to 1.23; p = 0.19). However, patients with a serum digoxin concentration ≥1.2 ng/ml had a 56% increased hazard of mortality (adjusted HR: 1.56; 95% CI: 1.20 to 2.04) compared with those not on digoxin. When analyzed as a continuous variable, serum digoxin concentration was associated with a 19% higher adjusted hazard of death for each 0.5-ng/ml increase (p = 0.0010); these results were similar for patients with and without heart failure. Compared with propensity score-matched control participants, the risk of death (adjusted HR: 1.78; 95% CI: 1.37 to 2.31) and sudden death (adjusted HR: 2.14; 95% CI: 1.11 to 4.12) was significantly higher in new digoxin users. CONCLUSIONS: In patients with AF taking digoxin, the risk of death was independently related to serum digoxin concentration and was highest in patients with concentrations ≥1.2 ng/ml. Initiating digoxin was independently associated with higher mortality in patients with AF, regardless of heart failure.
Authors: Jordan L Lacoste; Thomas W Szymanski; Juan Carlo Avalon; Galen Kabulski; Utkarsh Kohli; Nassir Marrouche; Atul Singla; Sudarshan Balla; Arshad Jahangir Journal: Am J Cardiovasc Drugs Date: 2022-03-30 Impact factor: 3.283