Relationship of serum digoxin concentration to mortality and morbidity in women in the digitalis investigation group trial: a retrospective analysis.

Pubmed ID: 16053964

Journal: Journal of the American College of Cardiology

Publication Date: Aug. 2, 2005

Affiliation: Department of Medicine and Radiology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27517, USA. kfa@med.unc.edu

MeSH Terms: Humans, Female, Aged, Age Factors, Middle Aged, Survival Analysis, Risk Assessment, Proportional Hazards Models, Heart Failure, Treatment Outcome, Confidence Intervals, Multivariate Analysis, Prognosis, Severity of Illness Index, Cardiotonic Agents, Retrospective Studies, Digoxin, Dose-Response Relationship, Drug, Probability, Drug Administration Schedule, Biological Availability, Maximum Tolerated Dose

Authors: Gheorghiade M, Adams KF, Patterson JH, Gattis WA, O'Connor CM, Lee CR, Schwartz TA

Cite As: Adams KF Jr, Patterson JH, Gattis WA, O'Connor CM, Lee CR, Schwartz TA, Gheorghiade M. Relationship of serum digoxin concentration to mortality and morbidity in women in the digitalis investigation group trial: a retrospective analysis. J Am Coll Cardiol 2005 Aug 2;46(3):497-504.

Studies:

Abstract

OBJECTIVES: The purpose of this study was to investigate the relationship of serum digoxin concentration (SDC) and outcomes in women with heart failure (HF). BACKGROUND: Controversy continues concerning the clinical utility of digoxin in women with HF. METHODS: Our analysis was retrospective with data from the Digitalis Investigation Group (DIG) trial. The principal study analysis reviewed 4,944 patients with HF due to systolic dysfunction who survived for at least 4 weeks (all 3,366 patients randomized to placebo and the 1,578 of 3,372 patients randomized to digoxin who had serum concentration measured 6 to 30 h [inclusive] after the last dose of study drug at 4 weeks). RESULTS: Continuous multivariable analysis demonstrated a significant linear relationship between SDC and mortality in women (p = 0.008) and men (p = 0.002, p = 0.766 for gender interaction). Averaging hazard ratios (HRs) across serum concentrations from 0.5 to 0.9 ng/ml in women produced a HR for death of 0.8 (95% confidence interval [CI] 0.62 to 1.13, p = 0.245) and for death or hospital stay for worsening HF of 0.73 (95% CI 0.58 to 0.93, p = 0.011). In contrast, SDCs from 1.2 to 2.0 ng/ml were associated with a HR for death for women of 1.33 (95% CI 1.001 to 1.76, p = 0.049). CONCLUSIONS: Retrospective analysis of data from the DIG trial indicates a beneficial effect of digoxin on morbidity and no excess mortality in women at serum concentrations from 0.5 to 0.9 ng/ml, whereas serum concentrations > or =1.2 ng/ml seem harmful.