Eplerenone and new‐onset diabetes in patients with mild heart failure: results from the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS‐HF)

Abstract

AimsNo studies have examined the effect of mineralocorticoid receptor antagonist therapy on new-onset diabetes. In addition, though the combination of diabetes and chronic heart failure (CHF) carries a poor prognosis, few studies have examined predictors of new-onset diabetes in those with CHF. Methods and resultsIn patients with symptomatically mild CHF who participated in the placebo-controlled Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure, we examined the effect of the aldosterone antagonist, eplerenone, on physician-diagnosed diabetes using univariate Cox proportional hazard analysis. To identify predictors of newonset diabetes (measures of glycaemia were not available), data from trial arms were combined and multivariate Cox proportional hazard analyses and receiver operating characteristic curve analyses were conducted. At baseline, the mean age of 1846 initially non-diabetic patients was 69 years and mean left ventricular ejection fraction was 26%. Over 21 months, 69 (3.7%) developed diabetes (33 on eplerenone, 36 on placebo). Eplerenone had no effect on new-onset diabetes [hazard ratio (HR) 0.94, 95% confidence interval (CI) 0.59 -1.52] and no effect on the composite of new-onset diabetes or mortality (HR 0.80, 95% CI 0.64-1.01). Independent predictors of new-onset diabetes included digoxin therapy, higher serum alanine aminotransferase, longer duration of heart failure, current or previous smoker, higher waist circumference, lower age, and higher systolic blood pressure with a combined c-statistic of 0.74. ConclusionsEplerenone had no effect on new-onset diabetes in patients with CHF, but further large-scale studies are required to address this question comprehensively. Commonly recorded parameters provided useful information for predicting new-onset diabetes.--

Cost-effectiveness of eplerenone in patients with systolic heart failure and mild symptoms

“…New-onset diabetes, heart transplants, dialysis and kidney transplants were not included in the model because the rates were low and either similar or the same for both trial arms, meaning that inclusion would not change the model results 10. In addition, consideration was given to modelling the change in NYHA class as time progressed, but as there was no significant change in NYHA class between the two arms (p=0.14), the majority of patients remained in class II (≥75% of patients at all time points up to month 42 were in NYHA class on both arms) and available evidence to extrapolate beyond the trial is limited, this was not included.…”

Mineralocorticoid receptors and the heart, multiple cell types and multiple mechanisms: a focus on the cardiomyocyte

“…MR antagonism reduces the risk of death and hospitalization in patients with chronic heart failure and can improve left ventricular hypertrophy regression and systolic blood pressure control in patients with mild heart failure when used in conjunction with an angiotensin-converting enzyme inhibitor [42,43]. More recently, the incidence of atrial fibrillation in patients with mild heart failure was effectively decreased by the second generation MR antagonist eplerenone [44][45][46]. These clinical trials clearly indicate the importance of including MR antagonists with current combination therapy in the treatment of heart failure and hypertension.…”

The Impact of Cardiovascular Drugs on Glycemic Control: A Review

“…75 Post-hoc analysis of the EMPHASIS-HF trial indicated that eplerenone had no impact on the incidence of diabetes (HR 0.90, 95% CI 0.59-1.52) in patients with left ventricular dysfunction after myocardial infarction. 76 …”