© 2006 European Society of Cardiology
Serum digoxin concentration and outcomes in women with heart failure: A bi-directional effect and a possible effect modification by ejection fraction
a Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Alabama at Birmingham Birmingham, Alabama, USA
b Section of Geriatrics, Veterans Affairs Medical Center Birmingham, Alabama, USA
c Department of Biostatistics, University of Alabama at Birmingham Birmingham, Alabama, USA
d Department of Epidemiology, University of Alabama at Birmingham Birmingham, Alabama, USA
e School of Public Health, Center for Heart Failure Research, University of Alabama at Birmingham Birmingham, Alabama, USA
f Center for Nursing Research, School of Nursing, University of Alabama at Birmingham Birmingham, Alabama, USA
g Cardiology Division, Department of Medicine, New York Medical College Valhalla, New York, USA
h National Heart, Lung and Blood Institute, National Institutes of Health Bethesda, Maryland, USA
* Corresponding author. University of Alabama at Birmingham, Division of Gerontology and Geriatric Medicine, 1530 3rd Avenue South, CH-19, Ste-219, Birmingham AL 35294-2041, USA. Tel.: +1 205 934 9632; fax: +1 205 975 7099. E-mail address: aahmed{at}uab.edu
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Abstract |
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Background: The association between serum digoxin concentration (SDC) and outcomes in women with heart failure (HF) has not been well studied.
Aims: To test the hypothesis that the effect of digoxin on outcomes in women with HF is bi-directional and dependent on SDC, as in men, and is modified by ejection fraction (EF).
Methods: We studied 1366 female participants of the Digitalis Investigation Group trial in whom data on SDC (ng/ml) were available. We calculated adjusted odds ratios (AOR) and Bonferroni-adjusted 97.5% confidence intervals (CI) for various outcomes at a median follow up of 41 months, in all women and stratified by EF 35%.
Results: Compared with placebo (26.9%), 40.3% with SDC
1.2 (AOR=1.80; CI=1.14–2.86; p=0.004) and 26.6% with SDC 0.5–1.1 (AOR=1.05; CI=0.73–1.51; p=0.762) died. Respective rates for HF-hospitalizations were: placebo (32.8%), SDC1.2 (38.0%) and SDC 0.5–1.1 (25.5%). For women with EF<35% (N=677), SDC 0.5–1.1 lowered odds for HF-hospitalizations (AOR=0.63; CI=0.39–1.00; p=0.026) without increasing odds for death (AOR=0.77; CI=0.47–1.26; p=0.233). In women with EF35% (N=689), SDC 0.5–1.1 had a borderline association with death (AOR=1.58; CI=0.92–2.72; p=0.058) but not with HF-hospitalization (AOR=0.95; CI=0.54–1.66; p=0.826).
Conclusions: As in men, in women with HF, digoxin has a bi-directional effect based on SDC, and the beneficial effects were significant only among women with EF<35%.
Key Words: Serum digoxin concentration • Outcomes • Women • Heart failure • Ejection fraction
Received April 21, 2005; Revised July 1, 2005; Accepted October 3, 2005