title: Effectiveness of digoxin in reducing one-year mortality in chronic heart failure in the Digitalis Investigation Group trial.
abstract: Post hoc analyses of the Digitalis Investigation Group (DIG) trial indicate that digoxin at low (0.5 to 0.9 ng/ml) serum digoxin concentration (SDC) reduces mortality, which is eliminated at higher (>or=1 ng/ml) SDC, and that low-dose digoxin (<or=0.125 mg/day) predicts low SDC. In the DIG trial, patients with ambulatory chronic systolic and diastolic heart failure (HF) (n = 7,788) in normal sinus rhythm receiving angiotensin-converting enzyme inhibitors and diuretics were randomized to receive placebo (n = 3,899) or digoxin (n = 3,889). The median dose of digoxin (0.25 mg/day) and the target SDC (0.8 to 2.5 ng/ml) were higher than what are currently recommended, which in part may explain the lack of long-term mortality benefit of digoxin in the DIG trial. To test this hypothesis, we examined the effect of digoxin on short-term outcomes; 1-year all-cause mortality occurred in 392 and 448 patients respectively in the digoxin and placebo groups (hazard ratio for digoxin 0.87, 95% confidence interval [CI] 0.76 to 0.995, p = 0.043). Respective hazard ratios for cardiovascular and HF deaths were 0.87 (95% CI 0.76 to 1.01, p = 0.072) and 0.66 (95% CI 0.52 to 0.85, p = 0.001). All-cause hospitalization occurred in 1,411 and 1,529 patients receiving digoxin and placebo respectively (hazard ratio 0.89, 95% CI 0.83 to 0.96, p = 0.002). Respective hazard ratios for cardiovascular and HF hospitalizations were 0.82 (95% CI 0.75 to 0.89, p <0.0001) and 0.59 (95% CI 0.52 to 0.66, p <0.0001). In conclusion, digoxin reduced 1-year mortality and hospitalization in patients with chronic HF receiving angiotensin-converting enzyme inhibitors and diuretics. Randomized clinical trials are needed to determine the effect of low-dose digoxin in contemporary patients with chronic HF.
authors.affiliation: University of Alabama at Birmingham, Birmingham, Alabama, USA. aahmed@uab.edu
authors.forename: Ali
authors.initials: A
authors.lastname: Ahmed
authors.forename: Finn
authors.initials: F
authors.lastname: Waagstein
authors.forename: Bertram
authors.initials: B
authors.lastname: Pitt
authors.forename: Michel
authors.initials: M
authors.lastname: White
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
authors.forename: James B
authors.initials: JB
authors.lastname: Young
authors.forename: Shahbudin H
authors.initials: SH
authors.lastname: Rahimtoola
mesh_terms: D000368:Aged; D002170:Canada / Q000453:epidemiology; D002316:Cardiotonic Agents / Q000008:administration & dosage*; D002423:Cause of Death / Q000639:trends; D002908:Chronic Disease; D004077:Digoxin / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015996:Survival Rate / Q000639:trends; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D002316:Cardiotonic Agents; D004077:Digoxin