Digoxin treatment in heart failure--unveiling risk by cluster analysis of DIG data.
BACKGROUND
Digoxin has been shown to reduce heart failure (HF) hospitalizations with no overall effect on mortality in HF patients. We used cluster analysis to delineate the clinical characteristics of HF patients in whom digoxin therapy was associated with improved or worsened clinical outcomes.


METHODS
The Digitalis Investigation Group (DIG) database was partitioned into 20 clusters. Multivariate Cox regression analyses was used, to identify clusters in which digoxin was associated with either an increase (Mortality(dig)HR>1), decrease (Mortality(dig)HR<1), or no association with all cause mortality (Mortality(dig)HR-NS); and separately, with an increase (HFA(dig)HR>1), decrease (HFA(dig)HR<1), or no association (HFA(dig)HR-NS) with HF admissions (HFA).


RESULTS
We identified 938 patients in the Mortality(dig)HR>1 group, 6818 patients in the Mortality(dig)HR-NS group, and none in Mortality(dig)HR<1 group. The Mortality(dig)HR>1 group had a higher prevalence of females, diabetes mellitus, hypertension, higher age, systolic blood pressure (SBP), heart rate and ejection fraction (EF), compared to the Mortality(dig)HR-NS group. Similarly, 6325 patients clustered in the HFA(dig)HR<1 group, 1431 patients in the HFA(dig)HR-NS group, and none in the HFA(dig)HR>1 group. The HFA(dig)HR-NS group had a higher prevalence of females and hypertension, higher SBP, body mass index and EF; and lower prevalence of peripheral edema and third heart sound, compared with the HFA(dig)HR<1 group.


CONCLUSIONS
Thus, the baseline characteristics of patients who did not have reduction in HF hospitalization or who had increased mortality were very similar and included females with hypertension, higher EF and higher SBP. Thus, use of digoxin in patients with this profile may need to be avoided.
Ather
Sameer
S
Baylor College of Medicine, Houston TX, United States.
Peterson
Leif E
LE
Divakaran
Vijay G
VG
Deswal
Anita
A
Ramasubbu
Kumudha
K
Giorgberidze
Irakli
I
Blaustein
Alvin
A
Wehrens
Xander H T
XH
Mann
Douglas L
DL
Bozkurt
Biykem
B
D000368:Aged; D016000:Cluster Analysis; D016208:Databases, Factual; D004077:Digoxin / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality* / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012737:Sex Factors; D016896:Treatment Outcome
D004077:Digoxin
Circulation. 2006 Aug 1;114(5):397-403
16864724
J Am Coll Cardiol. 2001 Sep;38(3):806-13
11527638
Control Clin Trials. 1996 Feb;17(1):77-97
8721804
Am J Cardiol. 2008 Nov 15;102(10):1356-60
18993155
Am J Cardiol. 2008 Dec 15;102(12):1681-6
19064024
Circ Heart Fail. 2008 Sep;1(3):208-9
19808292
N Engl J Med. 1997 Feb 20;336(8):525-33
9036306
J Am Coll Cardiol. 2005 Sep 20;46(6):e1-82
16168273
J Gerontol A Biol Sci Med Sci. 2007 Mar;62(3):323-9
17389731
N Engl J Med. 2002 Oct 31;347(18):1403-11
12409542
Circulation. 2009 Apr 14;119(14):1977-2016
19324967
JAMA. 2003 Feb 19;289(7):871-8
12588271
Int J Cardiol. 2009 Jan 9;131(2):149-50
19046787