Effects of digoxin at low serum concentrations on mortality and hospitalization in heart failure: a propensity-matched study of the DIG trial.

Pubmed ID: 17382417

Pubmed Central ID: PMC2474767

Journal: International journal of cardiology

Publication Date: Jan. 11, 2008

Affiliation: 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

MeSH Terms: Humans, Male, Female, Aged, Middle Aged, Heart Failure, Hospitalization, Retrospective Studies, Digoxin

Grants: K23 AG019211, R01 HL085561, 1-R01-HL085561-01, K23 AG019211-04, R01 HL085561-01, 1-K23-AG19211-04, P-50-HL077100, P50 HL077100

Authors: White M, Love TE, Ahmed A, Pitt B, Waagstein F, Rahimtoola SH, Braunwald E

Cite As: Ahmed A, Pitt B, Rahimtoola SH, Waagstein F, White M, Love TE, Braunwald E. Effects of digoxin at low serum concentrations on mortality and hospitalization in heart failure: a propensity-matched study of the DIG trial. Int J Cardiol 2008 Jan 11;123(2):138-46. Epub 2007 Mar 23.

Studies:

Abstract

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.