title: Digoxin therapy does not improve outcomes in patients with advanced heart failure on contemporary medical therapy.
abstract: BACKGROUND
  The impact of digoxin on outcomes of patients with advanced heart failure (HF) receiving optimal contemporary therapy is not known.
  
  
  RESULTS
  We retrospectively reviewed data of 455 advanced HF patients referred for transplant evaluation (age, 52+/-12 years; ejection fraction, 18.3+/-8%); 227 (49.9%) were on digoxin at baseline. Primary outcome was death (n=101), urgent transplantation (n=14), or ventricular assist device implantation (n=4); secondary outcomes included HF and all-cause hospitalizations. Digoxin use was evaluated (1) in the original cohort; (2) in a propensity score-matched subset (n=322); (3) as a time-dependent covariate; and (4) after adjustment for Seattle Heart Failure Score. Patients were on optimal therapy: angiotensin-II modulation, 92.5%; beta-blockers, 91.2%; aldosterone antagonists, 45.6%; and devices, 71.0%. After a median of 27 months, 83 of 277 (36.6%) patients treated with digoxin versus 36 of 228 (15.8%) patients without digoxin met primary outcome (hazard ratio [HR], 2.28; 95% CI, 1.51 to 3.43; P<0.001). This risk persisted in the matched subset (HR, 1.73; 95% CI, 1.09 to 2.75; P=0.021) and with time-varying digoxin use (HR, 2.05; 95% CI, 1.23 to 3.41; P=0.011). Digoxin was associated with higher risk among patients in sinus rhythm compared with atrial fibrillation. Digoxin was not associated with improvement in either all-cause or HF hospitalization rates. These results were similar across sex and race and when adjusted for Seattle Heart Failure Score and renal function.
  
  
  CONCLUSIONS
  This study suggests that digoxin therapy may be of no benefit in patients with advanced HF referred for cardiac transplantation who received optimal medical therapy. Treatment with digoxin should be used cautiously in such patients because of risk for adverse outcomes.
authors.affiliation: Center for Heart Failure Therapy, Emory University Hospital, Atlanta, GA 30322, USA.
authors.forename: Vasiliki V
authors.initials: VV
authors.lastname: Georgiopoulou
authors.forename: Andreas P
authors.initials: AP
authors.lastname: Kalogeropoulos
authors.forename: Grigorios
authors.initials: G
authors.lastname: Giamouzis
authors.forename: Syed A
authors.initials: SA
authors.lastname: Agha
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Rashad
authors.forename: Sana
authors.initials: S
authors.lastname: Waheed
authors.forename: Sonjoy
authors.initials: S
authors.lastname: Laskar
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Smith
authors.forename: Javed
authors.initials: J
authors.lastname: Butler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002316:Cardiotonic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D018592:Cross-Over Studies; D004077:Digoxin / Q000009:adverse effects / Q000627:therapeutic use*; D004452:Echocardiography; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology* / Q000601:surgery; D016027:Heart Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain; D012017:Referral and Consultation; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013318:Stroke Volume; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D002316:Cardiotonic Agents; D020097:Natriuretic Peptide, Brain; D004077:Digoxin