title: Digoxin and reduction in mortality and hospitalization in heart failure: a comprehensive post hoc analysis of the DIG trial.
abstract: OBJECTIVE
  To determine the effects of digoxin on all-cause mortality and heart failure (HF) hospitalizations, regardless of ejection fraction, accounting for serum digoxin concentration (SDC).
  
  
  RESULTS
  This comprehensive post-hoc analysis of the randomized controlled Digitalis Investigation Group trial (n=7788) focuses on 5548 patients: 1687 with SDC, drawn randomly at 1 month, and 3861 placebo patients, alive at 1 month. Overall, 33% died and 31% had HF hospitalizations during a 40-month median follow-up. Compared with placebo, SDC 0.5-0.9 ng/mL was associated with lower mortality [29 vs. 33% placebo; adjusted hazard ratio (AHR), 0.77; 95% confidence interval (CI), 0.67-0.89], all-cause hospitalizations (64 vs. 67% placebo; AHR, 0.85; 95% CI, 0.78-0.92) and HF hospitalizations (23 vs. 33% placebo; AHR, 0.62; 95% CI, 0.54-0.72). SDC> or =1.0 ng/mL was associated with lower HF hospitalizations (29 vs. 33% placebo; AHR, 0.68; 95% CI, 0.59-0.79), without any effect on mortality. SDC 0.5-0.9 reduced mortality in a wide spectrum of HF patients and had no interaction with ejection fraction >45% (P=0.834) or sex (P=0.917).
  
  
  CONCLUSIONS
  Digoxin at SDC 0.5-0.9 ng/mL reduces mortality and hospitalizations in all HF patients, including those with preserved systolic function. At higher SDC, digoxin reduces HF hospitalization but has no effect on mortality or all-cause hospitalizations.
authors.affiliation: University of Alabama at Birmingham, VA Medical Center, 1530 3rd Avenue South, CH-19, Ste-219, Birmingham, AL 35294-2041, USA. aahmed@uab.edu
authors.forename: Ali
authors.initials: A
authors.lastname: Ahmed
authors.forename: Michael W
authors.initials: MW
authors.lastname: Rich
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Love
authors.forename: Donald M
authors.initials: DM
authors.lastname: Lloyd-Jones
authors.forename: Inmaculada B
authors.initials: IB
authors.lastname: Aban
authors.forename: Wilson S
authors.initials: WS
authors.lastname: Colucci
authors.forename: Kirkwood F
authors.initials: KF
authors.lastname: Adams
authors.forename: Mihai
authors.initials: M
authors.lastname: Gheorghiade
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D002908:Chronic Disease; D004077:Digoxin / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D002316:Cardiotonic Agents; D004077:Digoxin