Intravenous Inotropes, Beta Blockers and Survival in Ambulatory Heart Failure Patients - A Contemporary Analysis of 3,311 Patients

Abstract

Purpose: Chronic inotrope therapy in advanced heart failure (HF) patients is most often considered palliative and associated with increased risk of mortality. Although chronic inotropes remain widely used questions remain as to current risk and the possible mitigating role of contemporary heart failure therapies. Here we examine survival on therapy of a large cohort of subjects treated with home inotrope therapy. Methods: Data were reviewed from the data base of a national home infusion provider. Subjects enrolled for home infusion of dobutamine or milrinone from 5/1/2009 to 6/14/2016 were included in the analysis. The data were fit to a cox proportional hazards model to evaluate the effect of inotrope and beta-blocker use on patients' survival, controlling for covariates age and gender. Step-wise elimination was used to construct the initial model, looking at the effects of Milrinone and supplemental beta-blockers relative to use of Dobutamine alone. Covariates in our model were found to vary continuously with time based on the distribution of Schoenfeld residuals after initial model fitting, so time-interacted co-variates were added to the model. Cox-Snell residuals were used to assess model fit. Data management and analysis were done in STATA 14.2. Results: The mean age of the cohort (n= 3,331) was 60.8±16.1 and 74% of the subjects were male. Milrinone was used in the majority of subjects (2,444 subjects (73.8%) and dobutamine was used in the remainder (867 subjects (26.2%). Eight-hundred and four (24.3%) subjects also received β blockers therapy. The mean duration of inotropic therapy was 133 days. Adjusted 180-day survival rate was 78.6%. The use of milrinone was associated with significantly better survival rate compared with dobutamine (HR= 0.557, p < 0.001). Of note β blocker therapy significantly improved survival rates with both agents (HR= 0.402, p = 0.016). Conclusion: Most available data on the use of chronic inotropes therapy was captured prior to our current era of neurohormonal-directed therapy and implanted defibrillators. In a large national contemporary cohort of advanced HF patients, milrinone was found to be superior to dobutamine and the addition of β blocker therapy was shown to further improve survival rates. Possible additive effects of other cardio-protective therapies should also be explored.