Effect of age on mortality, hospitalizations and response to digoxin in patients with heart failure: the DIG study

J Am Coll Cardiol. 2001 Sep;38(3):806-13. doi: 10.1016/s0735-1097(01)01442-5.


Objectives: This study was designed to determine the effect of increasing age on mortality, hospitalizations and digoxin side effects in patients with heart failure (HF), and to determine whether the effect of digoxin on clinical outcomes varies as a function of age.

Background: The incidence and prevalence of HF increase with advancing age, but there are limited data on the clinical course and response to specific therapeutic interventions in elderly patients with HF.

Methods: The Digitalis Investigation Group (DIG) study was a prospective, randomized clinical trial involving 7,788 patients with HF randomized to digoxin or placebo and followed for an average of 37 months. In the present analysis, patients were stratified into five age categories: <50 years (n = 841), 50 to 59 years (n = 1,545), 60 to 69 years (n = 2,885), 70 to 79 years (n = 2,092) and > or =80 years (n = 425). Interactions between age and the following clinical outcomes were examined: total mortality, all-cause hospitalizations, HF hospitalizations, the composite of HF death or HF hospitalization, hospitalization for suspected digoxin toxicity and withdrawal from therapy because of side effects.

Results: Increasing age was an independent risk factor for total mortality, all-cause hospitalization, HF hospitalization, HF death or hospital admission, hospitalization for suspected digoxin toxicity and withdrawal from digoxin therapy (all p < 0.001). However, there were no significant interactions between age and digoxin treatment with respect to any of the major clinical end points.

Conclusions: Increasing age is associated with progressively worse clinical outcomes in patients with HF. However, the beneficial effects of digoxin in reducing all-cause admissions, HF admissions, and HF death or hospitalization are independent of age. Thus, digoxin remains a useful agent for the adjunctive treatment of HF due to impaired left ventricular systolic function in patients of all ages.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Anti-Arrhythmia Agents / therapeutic use*
  • Digoxin / therapeutic use*
  • Female
  • Heart Failure / drug therapy*
  • Heart Failure / mortality*
  • Hospitalization / statistics & numerical data
  • Humans
  • Male
  • Middle Aged
  • Multicenter Studies as Topic
  • Prognosis
  • Randomized Controlled Trials as Topic
  • Risk Factors
  • Survival Analysis


  • Anti-Arrhythmia Agents
  • Digoxin