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European Heart Journal Advance Access originally published online on December 8, 2005
European Heart Journal 2006 27(2):178-186; doi:10.1093/eurheartj/ehi687
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© The European Society of Cardiology 2005. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Digoxin and reduction in mortality and hospitalization in heart failure: a comprehensive post hoc analysis of the DIG trial

Ali Ahmed1,*, Michael W. Rich2, Thomas E. Love3, Donald M. Lloyd-Jones4, Inmaculada B. Aban5, Wilson S. Colucci6, Kirkwood F. Adams7 and Mihai Gheorghiade4

1University of Alabama at Birmingham, VA Medical Center, 1530 3rd Avenue South, CH-19, Ste-219, Birmingham, AL35294-2041, USA
2Washington University, St Louis, MO, USA
3Case Western Reserve University, Cleveland, OH, USA
4Northwestern University, Chicago, IL, USA
5University of Alabama at Birmingham, Birmingham, AL, USA
6Boston University, Boston, MA, USA
7University of North Carolina, Chapel Hill, NC, USA

Received 17 October 2005; revised 14 November 2005; accepted 25 November 2005; online publish-ahead-of-print 8 December 2005.

* Corresponding author. Tel: +1 205 934 9632; fax: +1 205 975 7099. E-mail address: aahmed{at}uab.edu

See page 127 for the editorial comment on this article (doi:10.1093/eurheartj/ehi686)

Aims To determine the effects of digoxin on all-cause mortality and heart failure (HF) hospitalizations, regardless of ejection fraction, accounting for serum digoxin concentration (SDC).

Methods and results This comprehensive post-hoc analysis of the randomized controlled Digitalis Investigation Group trial (n=7788) focuses on 5548 patients: 1687 with SDC, drawn randomly at 1 month, and 3861 placebo patients, alive at 1 month. Overall, 33% died and 31% had HF hospitalizations during a 40-month median follow-up. Compared with placebo, SDC 0.5–0.9 ng/mL was associated with lower mortality [29 vs. 33% placebo; adjusted hazard ratio (AHR), 0.77; 95% confidence interval (CI), 0.67–0.89], all-cause hospitalizations (64 vs. 67% placebo; AHR, 0.85; 95% CI, 0.78–0.92) and HF hospitalizations (23 vs. 33% placebo; AHR, 0.62; 95% CI, 0.54–0.72). SDC≥1.0 ng/mL was associated with lower HF hospitalizations (29 vs. 33% placebo; AHR, 0.68; 95% CI, 0.59–0.79), without any effect on mortality. SDC 0.5–0.9 reduced mortality in a wide spectrum of HF patients and had no interaction with ejection fraction >45% (P=0.834) or sex (P=0.917).

Conclusions Digoxin at SDC 0.5–0.9 ng/mL reduces mortality and hospitalizations in all HF patients, including those with preserved systolic function. At higher SDC, digoxin reduces HF hospitalization but has no effect on mortality or all-cause hospitalizations.

Key Words: Digoxin • Heart failure • Preserved systolic function • Diastolic heart failure • Mortality • Hospitalization


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