Digoxin treatment in heart failure — Unveiling risk by cluster analysis of DIG data

BackgroundDigoxin 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.MethodsThe 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 (MortalitydigHR > 1), decrease (MortalitydigHR < 1), or no association with all cause mortality (MortalitydigHR − NS); and separately, with an increase (HFAdigHR > 1), decrease (HFAdigHR < 1), or no association (HFAdigHR − NS) with HF admissions (HFA).ResultsWe identified 938 patients in the MortalitydigHR > 1 group, 6818 patients in the MortalitydigHR − NS group, and none in MortalitydigHR < 1 group. The MortalitydigHR > 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 MortalitydigHR − NS group.Similarly, 6325 patients clustered in the HFAdigHR < 1 group, 1431 patients in the HFAdigHR − NS group, and none in the HFAdigHR > 1 group. The HFAdigHR − 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 HFAdigHR < 1 group.ConclusionThus, 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.