title: Digoxin and risk of death in adults with atrial fibrillation: the ATRIA-CVRN study.
abstract: BACKGROUND
  Digoxin remains commonly used for rate control in atrial fibrillation, but limited data exist supporting this practice and some studies have shown an association with adverse outcomes. We examined the independent association between digoxin and risks of death and hospitalization in adults with incident atrial fibrillation and no heart failure.
  
  
  RESULTS
  We performed a retrospective cohort study of 14,787 age, sex, and high-dimensional propensity score-matched adults with incident atrial fibrillation and no previous heart failure or digoxin use in the AnTicoagulation and Risk factors In Atrial fibrillation-Cardiovascular Research Network (ATRIA-CVRN) study within Kaiser Permanente Northern and Southern California. We examined the independent association between newly initiated digoxin and the risks of death and hospitalization using extended Cox regression. During a median 1.17 (interquartile range, 0.49-1.97) years of follow-up among matched patients with atrial fibrillation, incident digoxin use was associated with higher rates of death (8.3 versus 4.9 per 100 person-years; P<0.001) and hospitalization (60.1 versus 37.2 per 100 person-years; P<0.001). Incident digoxin use was independently associated with a 71% higher risk of death (hazard ratio, 1.71; 95% confidence interval, 1.52-1.93) and a 63% higher risk of hospitalization (hazard ratio, 1.63; 95% confidence interval, 1.56-1.71). Results were consistent in subgroups of age and sex and when using intent-to-treat or on-treatment analytic approaches.
  
  
  CONCLUSIONS
  In adults with atrial fibrillation, digoxin use was independently associated with higher risks of death and hospitalization. Given other available rate control options, digoxin should be used with caution in the management of atrial fibrillation.
authors.affiliation: From the Department of Medicine, Yale University School of Medicine, New Haven, CT (J.V.F.); Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena (K.R., T.N.H.); Departments of Medicine (M.F., A.S.G.) and Epidemiology and Biostatistics (A.S.G.), University of California, San Francisco; Division of Research, Kaiser Permanente Northern California, Oakland (N.U., N.K.P., A.S.G); Division of Cardiology, Kaiser Permanente Santa Clara Medical Center, CA (A.S.); Clinical Epidemiology Unit, Massachusetts General Hospital, Boston (L.H.B., D.E.S.); Harvard Medical School, Boston, MA (D.E.S.); and Department of Health Research and Policy, Stanford University School of Medicine, CA (A.S.G.).
authors.forename: James V
authors.initials: JV
authors.lastname: Freeman
authors.affiliation: From the Department of Medicine, Yale University School of Medicine, New Haven, CT (J.V.F.); Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena (K.R., T.N.H.); Departments of Medicine (M.F., A.S.G.) and Epidemiology and Biostatistics (A.S.G.), University of California, San Francisco; Division of Research, Kaiser Permanente Northern California, Oakland (N.U., N.K.P., A.S.G); Division of Cardiology, Kaiser Permanente Santa Clara Medical Center, CA (A.S.); Clinical Epidemiology Unit, Massachusetts General Hospital, Boston (L.H.B., D.E.S.); Harvard Medical School, Boston, MA (D.E.S.); and Department of Health Research and Policy, Stanford University School of Medicine, CA (A.S.G.).
authors.forename: Kristi
authors.initials: K
authors.lastname: Reynolds
authors.affiliation: From the Department of Medicine, Yale University School of Medicine, New Haven, CT (J.V.F.); Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena (K.R., T.N.H.); Departments of Medicine (M.F., A.S.G.) and Epidemiology and Biostatistics (A.S.G.), University of California, San Francisco; Division of Research, Kaiser Permanente Northern California, Oakland (N.U., N.K.P., A.S.G); Division of Cardiology, Kaiser Permanente Santa Clara Medical Center, CA (A.S.); Clinical Epidemiology Unit, Massachusetts General Hospital, Boston (L.H.B., D.E.S.); Harvard Medical School, Boston, MA (D.E.S.); and Department of Health Research and Policy, Stanford University School of Medicine, CA (A.S.G.).
authors.forename: Margaret
authors.initials: M
authors.lastname: Fang
authors.affiliation: From the Department of Medicine, Yale University School of Medicine, New Haven, CT (J.V.F.); Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena (K.R., T.N.H.); Departments of Medicine (M.F., A.S.G.) and Epidemiology and Biostatistics (A.S.G.), University of California, San Francisco; Division of Research, Kaiser Permanente Northern California, Oakland (N.U., N.K.P., A.S.G); Division of Cardiology, Kaiser Permanente Santa Clara Medical Center, CA (A.S.); Clinical Epidemiology Unit, Massachusetts General Hospital, Boston (L.H.B., D.E.S.); Harvard Medical School, Boston, MA (D.E.S.); and Department of Health Research and Policy, Stanford University School of Medicine, CA (A.S.G.).
authors.forename: Natalia
authors.initials: N
authors.lastname: Udaltsova
authors.affiliation: From the Department of Medicine, Yale University School of Medicine, New Haven, CT (J.V.F.); Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena (K.R., T.N.H.); Departments of Medicine (M.F., A.S.G.) and Epidemiology and Biostatistics (A.S.G.), University of California, San Francisco; Division of Research, Kaiser Permanente Northern California, Oakland (N.U., N.K.P., A.S.G); Division of Cardiology, Kaiser Permanente Santa Clara Medical Center, CA (A.S.); Clinical Epidemiology Unit, Massachusetts General Hospital, Boston (L.H.B., D.E.S.); Harvard Medical School, Boston, MA (D.E.S.); and Department of Health Research and Policy, Stanford University School of Medicine, CA (A.S.G.).
authors.forename: Anthony
authors.initials: A
authors.lastname: Steimle
authors.affiliation: From the Department of Medicine, Yale University School of Medicine, New Haven, CT (J.V.F.); Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena (K.R., T.N.H.); Departments of Medicine (M.F., A.S.G.) and Epidemiology and Biostatistics (A.S.G.), University of California, San Francisco; Division of Research, Kaiser Permanente Northern California, Oakland (N.U., N.K.P., A.S.G); Division of Cardiology, Kaiser Permanente Santa Clara Medical Center, CA (A.S.); Clinical Epidemiology Unit, Massachusetts General Hospital, Boston (L.H.B., D.E.S.); Harvard Medical School, Boston, MA (D.E.S.); and Department of Health Research and Policy, Stanford University School of Medicine, CA (A.S.G.).
authors.forename: Niela K
authors.initials: NK
authors.lastname: Pomernacki
authors.affiliation: From the Department of Medicine, Yale University School of Medicine, New Haven, CT (J.V.F.); Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena (K.R., T.N.H.); Departments of Medicine (M.F., A.S.G.) and Epidemiology and Biostatistics (A.S.G.), University of California, San Francisco; Division of Research, Kaiser Permanente Northern California, Oakland (N.U., N.K.P., A.S.G); Division of Cardiology, Kaiser Permanente Santa Clara Medical Center, CA (A.S.); Clinical Epidemiology Unit, Massachusetts General Hospital, Boston (L.H.B., D.E.S.); Harvard Medical School, Boston, MA (D.E.S.); and Department of Health Research and Policy, Stanford University School of Medicine, CA (A.S.G.).
authors.forename: Leila H
authors.initials: LH
authors.lastname: Borowsky
authors.affiliation: From the Department of Medicine, Yale University School of Medicine, New Haven, CT (J.V.F.); Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena (K.R., T.N.H.); Departments of Medicine (M.F., A.S.G.) and Epidemiology and Biostatistics (A.S.G.), University of California, San Francisco; Division of Research, Kaiser Permanente Northern California, Oakland (N.U., N.K.P., A.S.G); Division of Cardiology, Kaiser Permanente Santa Clara Medical Center, CA (A.S.); Clinical Epidemiology Unit, Massachusetts General Hospital, Boston (L.H.B., D.E.S.); Harvard Medical School, Boston, MA (D.E.S.); and Department of Health Research and Policy, Stanford University School of Medicine, CA (A.S.G.).
authors.forename: Teresa N
authors.initials: TN
authors.lastname: Harrison
authors.affiliation: From the Department of Medicine, Yale University School of Medicine, New Haven, CT (J.V.F.); Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena (K.R., T.N.H.); Departments of Medicine (M.F., A.S.G.) and Epidemiology and Biostatistics (A.S.G.), University of California, San Francisco; Division of Research, Kaiser Permanente Northern California, Oakland (N.U., N.K.P., A.S.G); Division of Cardiology, Kaiser Permanente Santa Clara Medical Center, CA (A.S.); Clinical Epidemiology Unit, Massachusetts General Hospital, Boston (L.H.B., D.E.S.); Harvard Medical School, Boston, MA (D.E.S.); and Department of Health Research and Policy, Stanford University School of Medicine, CA (A.S.G.).
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Singer
authors.affiliation: From the Department of Medicine, Yale University School of Medicine, New Haven, CT (J.V.F.); Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena (K.R., T.N.H.); Departments of Medicine (M.F., A.S.G.) and Epidemiology and Biostatistics (A.S.G.), University of California, San Francisco; Division of Research, Kaiser Permanente Northern California, Oakland (N.U., N.K.P., A.S.G); Division of Cardiology, Kaiser Permanente Santa Clara Medical Center, CA (A.S.); Clinical Epidemiology Unit, Massachusetts General Hospital, Boston (L.H.B., D.E.S.); Harvard Medical School, Boston, MA (D.E.S.); and Department of Health Research and Policy, Stanford University School of Medicine, CA (A.S.G.). Alan.S.Go@kp.org.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Go
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects*; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D002140:California; D016009:Chi-Square Distribution; D004077:Digoxin / Q000009:adverse effects*; D005260:Female; D006760:Hospitalization; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D057216:Propensity Score; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000889:Anti-Arrhythmia Agents; D004077:Digoxin
keywords: arrhythmia; atrial fibrillation; digoxin; morbidity; mortality