Effects of Digoxin in high risk chronic heart failure patients in the DIG trial: a pre specified subgroup analysis

摘要

Background: Despite a class IIa indication for Digoxin use inheart failure by both ACC/AHA and ESC, its use has been goingdown in the last decade. One of the reasons has been theresult of The Digitalis Investigation Group (DIG) Trial. Thisrandomized controlled study in 6800 patients of ambulatoryheart failure (age 21 yrs, LV ejection fraction 45%, normalsinus rhythm) failed to show a mortality benefit from Digoxinuse. It did however demonstrate a reduction in hospitalizationsoverall and for worsening heart failure.Objectives: Since more than half of these heart failurepatients had high risk features characterized by class IIIeIVsymptoms, or ejection fraction lower than 25% or with a CTratio more than 55% a subanalysis of DIG Trial data wasplanned to see the effect of Digoxin in this subcategory interms of the composite endpoints of mortality or hospitalizationsover 2 years.Patients and methods: From the dataset of DIG patientsobtained from the National Heart Blood and Lung Institute,4367 high risk patients (mean age 64 years, 26% females) wereanalyzed. There were 2223 (51%) with class IIIeIV symptoms,2256 (52%) with LVEF 55%. Allhigh risk feature groups were analyzed separately and alsotogether.Pearson chi square and Wicoxon rank sum tests showed nosignificant difference in the baseline characteristics, includingmedical history, cause of heart failure and drug use betweenthe three groups (except that dyspnea was more in the thosewith class IIeIV symptoms). Outcomes were assessed usingKaplan Meier and Cox proportional hazard analyses. Statisticalanalysis was two tailed in all cases and a p value of 55%, absolute riskreduction being 2%, 6% and 4% respectively. There was anabsolute risk reduction of 3% in favor of Digoxin if any of thethree high risk feature was present (p 0.001). Also, significantlyless patients receiving Digoxin experienced heartfailure related mortality or hospitalization. HR was 0.65(p 55%(absolute risk reductionof 11%, 12%, 11%, 10% respectively and 11% when anyof the high risk features were present; p ?0.001).Conclusion: Digoxin use reduced the primary endpoint ofall-cause and heart failure mortality or hospitalizations inhigh risk heart failure patients. This effect was primarilydriven by reduction in hospitalizations with no significanteffect on mortality.