Author + information
- Received November 12, 2004
- Revision received February 8, 2005
- Accepted February 14, 2005
- Published online August 2, 2005.
- Kirkwood F. Adams Jr, MD, FACC⁎,⁎ (, )
- J. Herbert Patterson, PharmD†,
- Wendy A. Gattis, PharmD§,
- Christopher M. O’Connor, MD, FACC§,
- Craig R. Lee, PharmD†,
- Todd A. Schwartz, DrPH‡ and
- Mihai Gheorghiade, MD, FACC∥
- ↵⁎Reprint requests and correspondence:
Dr. Kirkwood F. Adams, Jr., UNC Heart Failure Program, 6110 Falconbridge Road, Suite 101, Chapel Hill, North Carolina 27517.
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 ≥1.2 ng/ml seem harmful.
Drs. Adams, Patterson, O’Connor, Gattis, and Gheorghiade have or have had consulting, research relationships, and speaker bureau support from GlaxoSmithKline related to carvedilol but not digoxin. The DIG is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the DIG Study Investigators. This manuscript was not prepared in collaboration with investigators of the DIG Study and does not necessarily reflect the opinions or views of the DIG Study or the NHLBI. The authors would like to dedicate this manuscript to the late Dr. Thomas W. Smith, whose sense of scholarship, high ideals, good nature, and untiring investigative efforts related to the use of digitalis in patients with heart failure inspired this work.
- Received November 12, 2004.
- Revision received February 8, 2005.
- Accepted February 14, 2005.
- American College of Cardiology Foundation