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J Am Coll Cardiol, 2001; 38:806-813
© 2001 by the American College of Cardiology Foundation
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CLINICAL STUDY: HEART FAILURE

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

Michael W. Rich, MD, FACC*, Frances McSherry, MS{dagger}, William O. Williford, PhD{dagger}, Salim Yusuf, MD, FACC{ddagger} for the Digitalis Investigation Group

* Cardiovascular Division, Washington University, St. Louis, Missouri, USA
{dagger} Veterans Administration Medical Center, Perry Point, Maryland, USA
{ddagger} Hamilton General Hospital, Toronto, Ontario, Canada

Manuscript received December 31, 2000; revised manuscript received May 14, 2001, accepted May 23, 2001.

Reprint requests and correspondence: Dr. Michael W. Rich, Associate Professor of Medicine, Washington University School of Medicine, Cardiovascular Division, 660 South Euclid Avenue, Box 8086, St. Louis, Missouri 63110
mrich{at}im.wustl.edu

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 ≥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.

Abbreviations and Acronyms
  ACE = angiotensin-converting enzyme
  DIG = Digitalis Investigation Group
  HF = heart failure
  LVEF = left ventricular ejection fraction




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