Effect of oral digoxin in high-risk heart failure patients: A pre-specified subgroup analysis of the DIG trial

Mihai Gheorghiade, Kanan Patel, Gerasimos Filippatos, Stefan D. Anker, Dirk J. Van Veldhuisen, John G.F. Cleland, Marco Metra, Inmaculada B. Aban, Stephen J. Greene, Kirkwood F. Adams, John J.V. McMurray, Ali Ahmed*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

59 Scopus citations


AimsIn the Digitalis Investigation Group (DIG) trial, digoxin reduced mortality or hospitalization due to heart failure (HF) in several pre-specified high-risk subgroups of HF patients, but data on protocol-specified 2-year outcomes were not presented. In the current study, we examined the effect of digoxin on HF death or HF hospitalization and all-cause death or all-cause hospitalization in high-risk subgroups during the protocol-specified 2 years of post-randomization follow-up.Methods and resultsIn the DIG trial, 6800 ambulatory patients with chronic HF, normal sinus rhythm, and LVEF ≤45% (mean age 64 years, 26% women, 17% non-whites) were randomized to receive digoxin or placebo. The three high-risk groups were defined as NYHA class III-IV symptoms (n = 2223), LVEF <25% (n = 2256), and cardiothoracic ratio (CTR) >55% (n = 2345). In all three high-risk subgroups, compared with patients in the placebo group, those in the digoxin group had a significant reduction in the risk of the 2-year composite endpoint of HF mortality or HF hospitalization: NYHA III-IV [hazard ratio (HR) 0.65; 95% confidence interval (CI) 0.57-0.75; P < 0.001], LVEF <25% (HR 0.61; 95% CI 0.53-0.71; P < 0.001), and CTR >55% (HR 0.65; 95% CI 0.57-0.75; P < 0.001). Digoxin-associated HRs (95% CI) for 2-year all-cause mortality or all-cause hospitalization for subgroups with NYHA III-IV, LVEF <25%, and CTR >55% were 0.88 (0.80-0.97; P = 0.012), 0.84 (0.76-0.93; P = 0.001), and 0.85 (0.77-0.94; P = 0.002), respectively. ConclusionsDigoxin improves outcomes in chronic HF patients with NYHA class III-IV, LVEF <25%, or CTR >55%, and should be considered in these patients. All rights reserved.

Original languageEnglish (US)
Pages (from-to)551-559
Number of pages9
JournalEuropean Journal of Heart Failure
Issue number5
StatePublished - May 2013


  • Digoxin
  • Heart Failure
  • High risk
  • Morbidity
  • Mortality

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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