title: Digoxin treatment in heart failure--unveiling risk by cluster analysis of DIG data.
abstract: 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.
authors.affiliation: Baylor College of Medicine, Houston TX, United States.
authors.forename: Sameer
authors.initials: S
authors.lastname: Ather
authors.forename: Leif E
authors.initials: LE
authors.lastname: Peterson
authors.forename: Vijay G
authors.initials: VG
authors.lastname: Divakaran
authors.forename: Anita
authors.initials: A
authors.lastname: Deswal
authors.forename: Kumudha
authors.initials: K
authors.lastname: Ramasubbu
authors.forename: Irakli
authors.initials: I
authors.lastname: Giorgberidze
authors.forename: Alvin
authors.initials: A
authors.lastname: Blaustein
authors.forename: Xander H T
authors.initials: XH
authors.lastname: Wehrens
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Mann
authors.forename: Biykem
authors.initials: B
authors.lastname: Bozkurt
mesh_terms: 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
chemical_list: D004077:Digoxin
references.citation: Circulation. 2006 Aug 1;114(5):397-403
references.pmid: 16864724
references.citation: J Am Coll Cardiol. 2001 Sep;38(3):806-13
references.pmid: 11527638
references.citation: Control Clin Trials. 1996 Feb;17(1):77-97
references.pmid: 8721804
references.citation: Am J Cardiol. 2008 Nov 15;102(10):1356-60
references.pmid: 18993155
references.citation: Am J Cardiol. 2008 Dec 15;102(12):1681-6
references.pmid: 19064024
references.citation: Circ Heart Fail. 2008 Sep;1(3):208-9
references.pmid: 19808292
references.citation: N Engl J Med. 1997 Feb 20;336(8):525-33
references.pmid: 9036306
references.citation: J Am Coll Cardiol. 2005 Sep 20;46(6):e1-82
references.pmid: 16168273
references.citation: J Gerontol A Biol Sci Med Sci. 2007 Mar;62(3):323-9
references.pmid: 17389731
references.citation: N Engl J Med. 2002 Oct 31;347(18):1403-11
references.pmid: 12409542
references.citation: Circulation. 2009 Apr 14;119(14):1977-2016
references.pmid: 19324967
references.citation: JAMA. 2003 Feb 19;289(7):871-8
references.pmid: 12588271
references.citation: Int J Cardiol. 2009 Jan 9;131(2):149-50
references.pmid: 19046787