Digoxin and Mortality in Patients With Atrial Fibrillation

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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.

Original languageEnglish
Pages (from-to)1063-1074
Number of pages12
JournalJournal of the American College of Cardiology
Volume71
Issue number10
DOIs
Publication statusPublished - Mar 13 2018

Fingerprint

Digoxin
Atrial Fibrillation
Mortality
Confidence Intervals
Serum
Heart Failure
Social Adjustment
Risk-Taking
Sudden Death

Keywords

  • atrial fibrillation
  • digoxin
  • heart failure
  • mortality

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Digoxin and Mortality in Patients With Atrial Fibrillation. / for the.

In: Journal of the American College of Cardiology, Vol. 71, No. 10, 13.03.2018, p. 1063-1074.

Research output: Contribution to journalArticle

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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.",
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author = "{for the} and Lopes, {Renato D.} and Roberto Rordorf and {De Ferrari}, {Gaetano M.} and Sergio Leonardi and Laine Thomas and Wojdyla, {Daniel M.} and Peter Ridefelt and Lawrence, {John H.} and {De Caterina}, Raffaele and Dragos Vinereanu and Michael Hanna and Greg Flaker and Al-Khatib, {Sana M.} and Hohnloser, {Stefan H.} and Alexander, {John H.} and Granger, {Christopher B.} and Lars Wallentin",
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AU - Lopes, Renato D.

AU - Rordorf, Roberto

AU - De Ferrari, Gaetano M.

AU - Leonardi, Sergio

AU - Thomas, Laine

AU - Wojdyla, Daniel M.

AU - Ridefelt, Peter

AU - Lawrence, John H.

AU - De Caterina, Raffaele

AU - Vinereanu, Dragos

AU - Hanna, Michael

AU - Flaker, Greg

AU - Al-Khatib, Sana M.

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N2 - 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.

AB - 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.

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