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


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.
Ahmed
Ali
A
University of Alabama at Birmingham, 1530 3rd Ave S, CH-19, Suite 219, Birmingham AL 35294-2041, USA. aahmed@uab.edu
Rich
Michael W
MW
Fleg
Jerome L
JL
Zile
Michael R
MR
Young
James B
JB
Kitzman
Dalane W
DW
Love
Thomas E
TE
Aronow
Wilbert S
WS
Adams
Kirkwood F
KF
Gheorghiade
Mihai
M
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002316:Cardiotonic Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D004077:Digoxin / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D004232:Diuretics / Q000627:therapeutic use; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality* / Q000503:physiopathology; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D008875:Middle Aged; D009017:Morbidity; D012849:Sinoatrial Node / Q000502:physiology; D013318:Stroke Volume / Q000502:physiology; D015996:Survival Rate; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D002316:Cardiotonic Agents; D004232:Diuretics; D004077:Digoxin