Clinical Trials The Effect of Digoxin on the Quality of Life in Patients With Heart Failure ELLIS LADER, MD,* DEBRA EGAN, PhD, † SALLY HUNSBERGER, PhD, ‡ REKHA GARG, MD, MS, § SUSAN CZAJKOWSKI, PhD, † FRANCES MCSHERRY, MS || New York, New York; Bethesda, Maryland; Indianapolis, Indiana; Perry Point, Maryland ABSTRACT Background: The Digitalis Investigation Group (DIG) trial was a randomized double-blind placebo-controlled study that examined the effect of digoxin on mortality in 7,788 patients with heart failure and sinus rhythm. A prespecified substudy evaluated the effect of digoxin therapy on health-related quality of life (HQOL) in a subset of these patients. Methods: Patients in the DIG trial had clinical heart failure and were randomized to either digoxin or placebo in addition to their baseline diuretic and angiotensin-converting enzyme therapy (n = 7,788). The patients in this substudy had HQOL measured using a self- administered questionnaire employing scales that measured general health, physical func- tioning, depression, anger, anxiety, life satisfaction, and disease specific measures. A subjective assessment by the investigator and a 6-minute walk test evaluated functional status. HQOL was measured at baseline and at the 4- and 12-month follow-up visits. Results: The baseline characteristics of the patients in the quality of life substudy (n = 589) were comparable to the remaining patients in the study (n = 7,199) by age and other clinical measures, including history of prior myocardial infarction or etiology of heart failure; heart failure was of shorter duration and the ejection fraction was slightly better than in the main trial. Within the substudy, patients receiving digoxin (n = 298) or placebo (n = 291) were also similar in baseline characteristics. There was no statistically significant difference in any HQOL measure between the digoxin and the placebo groups at baseline. At the 4-month visit, only perceived health was improved in the digoxin group. At 12 months, there was no statistically significant difference in perceived health, physical functioning, Minnesota Living with Heart Failure, depression, anxiety, anger, Ladder of Life, or the 6-minute walk between the digoxin and placebo groups. Conclusion: In this subset of the DIG population, digoxin therapy had no effect on the HQOL in patients with heart failure in sinus rhythm. Key Words: Exercise tolerance, 6-minute walk test, DIG trial. From the *New York University School of Medicine, New York, New York; † National Heart, Lung, and Blood Institute and ‡ National Cancer Institute, National Institutes of Health, Bethesda, Maryland; § Eli Lilly and Company, Indianopolis, Indiana; and || Perry Point VA Medical Center, Perry Point, Maryland. Manuscript received May 14, 2001; revised manuscript received November 6, 2002; revised manuscript accepted November 11, 2002. The study was conducted by the National Heart, Lung, and Blood Institute of the National Institutes of Health, and the Department of Veterans Affairs Cooperative Studies program; Glaxo Wellcome supplied digoxin and placebo. Reprint requests: Cooperative Studies Program Coordinating Center, Research–151 E, PO Box 1010, Perry Point, MD 21902-1010. Copyright 2003, Elsevier Inc. All rights reserved. 1071-9164/03/0901–0002$30.00/0 doi:10.1054/jcaf.2003.7 Journal of Cardiac Failure Vol. 9 No. 1 2003 4