Effects of digoxin at low serum concentrations on mortality and hospitalization in heart failure: a propensity-matched study of the DIG trial.
BACKGROUND
In heart failure (HF), digoxin at low serum digoxin concentrations (SDC) reduces all-cause mortality and HF hospitalizations. However, the effects of digoxin on other cause-specific outcomes have not been studied in a propensity-matched cohort.


METHODS
The Digitalis Investigation Group trial, conducted during 1991-1993, enrolled 7788 ambulatory chronic HF patients. This analysis focuses on 4843 patients: 982 receiving digoxin with low (0.5-0.9 ng/ml) SDC at one month, and 3861 receiving placebo and alive at one month. Propensity scores for low SDC, calculated using a non-parsimonious multivariable logistic regression model, were used to match 982 low-SDC patients with 982 placebo patients. Matched Cox regression analyses were used to determine the effect of digoxin at low SDC on outcomes.


RESULTS
All-cause mortality occurred in 315 placebo (rate, 1071/10,000 person-years) and 288 low-SDC digoxin (rate, 871/10,000 person-years) patients, respectively, during 2940 and 3305 years of follow up (hazard ratio {HR}, 0.81, 95% confidence interval {CI}, 0.68-0.98; p=0.028). Cardiovascular hospitalizations occurred in 493 placebo (2359/10,000 person-year) and 471 low-SDC digoxin (1963/10,000 person-year) patients, respectively during 2090 and 2399 years of follow up (HR, 0.82, 95% CI, 0.70-0.95; P=0.010). Low-SDC digoxin to placebo HR (95%CI) for HF mortality and HF hospitalizations were respectively, 0.65 (0.45-0.92; P=0.015) and 0.63 (0.52-0.77; P<0.0001). Low-dose digoxin (< or = 0.125 mg/day) was the strongest independent predictor of low SDC (adjusted odd ratio, 2.07, 95% CI 1.54-2.80).


CONCLUSIONS
Digoxin at low SDC significantly reduced mortality and hospitalizations in ambulatory chronic systolic and diastolic HF patients.
Ahmed
Ali
A
University of Alabama at Birmingham, 1530 3rd Ave South, CH-19, Ste-219 and VA Medical Center, Birmingham, AL 35294-2041, USA. aahmed@uab.edu
Pitt
Bertram
B
Rahimtoola
Shahbudin H
SH
Waagstein
Finn
F
White
Michel
M
Love
Thomas E
TE
Braunwald
Eugene
E
D000368:Aged; D004077:Digoxin / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000401:mortality*; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
D004077:Digoxin