title: Potential effects of digoxin on long-term renal and clinical outcomes in chronic heart failure.
abstract: BACKGROUND
  Digitalis glycosides are known to improve the hemodynamic and neurohormonal perturbations that contribute to heart failure (HF)-induced renal dysfunction (RD). The objective of this study was to determine if randomization to digoxin is associated with improvement in renal function (IRF) and to evaluate if patients with digoxin-induced IRF have improved clinical outcomes.
  
  
  RESULTS
  Patients in the Digitalis Investigation Group (DIG) dataset with protocol-driven 1-year serum creatinine levels (performed in a central laboratory; n = 980) were studied. IRF was defined as a postrandomization ≥20% increase in estimated glomerular filtration rate (eGFR). IRF occurred in 15.5% of the population (mean improvement in eGFR 34.5 ± 15.4%) and was more common in patients randomized to digoxin (adjusted odds ratio 1.6; P = .02). In patients without IRF, digoxin was not associated with reduced death or hospitalization (adjusted hazard ratio [HR] 0.96, 95% CI 0.8-1.2; P = .67). However, in the group with IRF, digoxin was associated with substantially improved hospitalization-free survival (adjusted HR 0.49, 95% CI 0.3-0.8; P = .006; P interaction = .026).
  
  
  CONCLUSIONS
  In this subset of the DIG trial, digoxin was associated with long-term improvement in kidney function and, in patients demonstrating this favorable renal response, reduction in death or hospitalization. Additional research is necessary to confirm these hypothesis-generating findings.
authors.affiliation: Department of Internal Medicine and Program of Applied Translational Research, Yale University School of Medicine, New Haven, Connecticut, USA. jeffrey.testani@yale.edu
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Testani
authors.forename: Meredith A
authors.initials: MA
authors.lastname: Brisco
authors.forename: W H Wilson
authors.initials: WH
authors.lastname: Tang
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Kimmel
authors.forename: Anjali
authors.initials: A
authors.lastname: Tiku-Owens
authors.forename: Paul R
authors.initials: PR
authors.lastname: Forfia
authors.forename: Steven G
authors.initials: SG
authors.lastname: Coca
mesh_terms: D059347:Cardio-Renal Syndrome / Q000188:drug therapy*; D002316:Cardiotonic Agents / Q000097:blood / Q000627:therapeutic use*; D003404:Creatinine / Q000032:analysis; D004077:Digoxin / Q000097:blood / Q000627:therapeutic use*; D005260:Female; D005919:Glomerular Filtration Rate; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D002316:Cardiotonic Agents; D004077:Digoxin; D003404:Creatinine