Effects of digoxin on morbidity and mortality in diastolic heart failure: the ancillary digitalis investigation group trial.

Pubmed ID: 16864724

Pubmed Central ID: PMC2628473

Journal: Circulation

Publication Date: Aug. 1, 2006

Affiliation: University of Alabama at Birmingham, 1530 3rd Ave S, CH-19, Suite 219, Birmingham AL 35294-2041, USA. aahmed@uab.edu

MeSH Terms: Humans, Male, Female, Aged, Middle Aged, Heart Failure, Hospitalization, Treatment Outcome, Blood Pressure, Angiotensin-Converting Enzyme Inhibitors, Cardiotonic Agents, Morbidity, Survival Rate, Stroke Volume, Diuretics, Digoxin, Sinoatrial Node

Grants: K23 AG019211, K23 AG019211-04, 1-K23-AG19211-04, R37 AG018915

Authors: Love TE, Aronow WS, Ahmed A, Gheorghiade M, Young JB, Rich MW, Zile MR, Adams KF, Fleg JL, Kitzman DW

Cite As: Ahmed A, Rich MW, Fleg JL, Zile MR, Young JB, Kitzman DW, Love TE, Aronow WS, Adams KF Jr, Gheorghiade M. Effects of digoxin on morbidity and mortality in diastolic heart failure: the ancillary digitalis investigation group trial. Circulation 2006 Aug 1;114(5):397-403. Epub 2006 Jul 24.



BACKGROUND: About half of the 5 million heart failure patients in the United States have diastolic heart failure (clinical heart failure with normal or near-normal ejection fraction). Except for candesartan, no drugs have been tested in randomized clinical trials in these patients. Although digoxin was tested in an appreciable number of diastolic heart failure patients in the Digitalis Investigation Group ancillary trial, detailed findings from this important study have not previously been published. METHODS AND RESULTS: Ambulatory chronic heart failure patients (n = 988) with normal sinus rhythm and ejection fraction > 45% (median, 53%) from the United States and Canada (1991 to 1993) were randomly assigned to digoxin (n = 492) or placebo (n = 496). During follow-up with a mean length of 37 months, 102 patients (21%) in the digoxin group and 119 patients (24%) in the placebo group (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.63 to 1.07; P = 0.136) experienced the primary combined outcome of heart failure hospitalization or heart failure mortality. Digoxin had no effect on all-cause or cause-specific mortality or on all-cause or cardiovascular hospitalization. Use of digoxin was associated with a trend toward a reduction in hospitalizations resulting from worsening heart failure (HR, 0.79; 95% CI, 0.59 to 1.04; P = 0.094) but also a trend toward an increase in hospitalizations for unstable angina (HR, 1.37; 95% CI, 0.99 to 1.91; P = 0.061). CONCLUSIONS: In ambulatory patients with chronic mild to moderate diastolic heart failure and normal sinus rhythm receiving angiotensin-converting enzyme inhibitor and diuretics, digoxin had no effect on natural history end points such as mortality and all-cause or cardiovascular hospitalizations.