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Effectiveness of digoxin in reducing one-year mortality in chronic heart failure in the Digitalis Investigation Group

1, Ali Ahmed, Finn Waagstein

  • 1University of Alabama at Birmingham, Birmingham, Alabama, USA. aahmed@uab.edu

The American Journal of Cardiology
|December 23, 2008
PubMed

Insights

Low-dose digoxin significantly reduced mortality and hospitalization in patients with chronic heart failure (HF). Higher serum digoxin concentrations negated this benefit, indicating a narrow therapeutic window for digoxin in HF management.

Area of Science:

  • Cardiology
  • Pharmacology

Background:

  • Post hoc analyses of the Digitalis Investigation Group (DIG) trial suggest digoxin reduces mortality at low serum digoxin concentrations (SDC) (0.5-0.9 ng/ml).
  • Higher SDCs (>=1 ng/ml) eliminated the mortality benefit, and low-dose digoxin (
  • The original DIG trial used higher median digoxin doses and target SDCs than currently recommended, potentially explaining the lack of long-term mortality benefit.

Purpose of the Study:

  • To test the hypothesis that higher SDCs in the DIG trial obscured the mortality benefit of digoxin.
  • To examine the effect of digoxin on short-term outcomes (1-year mortality and hospitalization) in patients with chronic heart failure (HF).
  • To evaluate digoxin's efficacy in patients receiving contemporary HF therapies like angiotensin-converting enzyme inhibitors and diuretics.

Main Methods:

  • Analysis of data from the DIG trial, which randomized 7,788 patients with chronic HF in normal sinus rhythm to placebo or digoxin.
  • Patients were receiving angiotensin-converting enzyme inhibitors and diuretics.
  • Short-term outcomes, including 1-year all-cause mortality and hospitalization, were assessed.

Main Results:

  • Digoxin use was associated with a significant reduction in 1-year all-cause mortality (hazard ratio [HR] 0.87, p=0.043).
  • Digoxin significantly reduced cardiovascular and HF hospitalizations (HR 0.82, p<0.0001 and HR 0.59, p<0.0001, respectively).
  • A trend towards reduced cardiovascular deaths was observed (HR 0.87, p=0.072), and HF deaths were significantly reduced (HR 0.66, p=0.001).

Conclusions:

  • Digoxin demonstrated a significant benefit in reducing 1-year mortality and hospitalization in patients with chronic HF when used with ACE inhibitors and diuretics.
  • These findings support the potential efficacy of digoxin at optimized, lower serum concentrations.
  • Further randomized clinical trials are warranted to confirm the effect of low-dose digoxin in contemporary chronic HF populations.

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