Effect of eplerenone in patients with heart failure and reduced ejection fraction: potential effect modification by abdominal obesity: insight from the EMPHASIS-HF trial

Olivier, A. et al. (2017) Effect of eplerenone in patients with heart failure and reduced ejection fraction: potential effect modification by abdominal obesity: insight from the EMPHASIS-HF trial. European Journal of Heart Failure, 19(9), pp. 1186-1197. (doi: 10.1002/ejhf.792) (PMID:28303624)

138676.pdf - Accepted Version



Aims: An excessive production of aldosterone influences outcome in patients with heart failure (HF) and in obese patients. Findings from laboratory studies suggest that chronic aldosterone blockade maybe more beneficial in abdominally obese HF-prone rats. In the current study, we investigated if the clinical response to a mineralocorticoid receptor antagonist in mildly symptomatic HF patients varied by abdominal obesity. Methods and results: A total of 2587 NYHA class II, reduced ejection fraction HF (HFrEF) patients enrolled in the EMPHASIS-HF trial were randomly assigned to eplerenone and placebo. In this post hoc analysis, patients were categorized according to waist circumference (WC) (normal if WC < 102 cm in men and < 88 cm in women; abdominal obesity if WC ≥ 102 cm in men and ≥ 88 cm women). The potential statistical interaction between the treatment and WC was assessed on the primary endpoint of death from cardiovascular causes or hospitalization for HF and other secondary endpoints. Over a median follow-up of 21 months, a significant benefit of eplerenone for the primary outcome was noted in both normal [hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.61–0.98, P = 0.03] and increased (HR 0.48, 95% CI 0.37–0.63, P < 0.0001) WC subgroups, but the latter patients appeared to receive greater benefit than patients with normal WC (P for interaction = 0.01). This suggests a significant quantitative (treatment effect varies in magnitude by subgroup, but is always in same direction) rather than a qualitative interaction (direction of the treatment effect varies by subgroup) between eplerenone and WC in the adjusted analysis. Mean doses of eplerenone, blood pressure and serum potassium changes and adverse events were similar between WC subgroups. Conclusion: In EMPHASIS-HF, eplerenone improved outcomes in HFrEF patients with and without abdominal obesity, although the benefit appeared to be more pronounced among those with abdominal obesity. The findings are potentially hypothesis generating and need to be replicated in other HFrEF populations.

Item Type:Articles
Glasgow Author(s) Enlighten ID:McMurray, Professor John
Authors: Olivier, A., Pitt, B., Girerd, N., Lamiral, Z., Machu, J.-L., McMurray, J. J.V., Swedberg, K., van Veldhuisen, D. J., Collier, T. J., Pocock, S. J., Rossignol, P., Zannad, F., and Pizard, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:European Journal of Heart Failure
ISSN (Online):1879-0844
Published Online:16 March 2017
Copyright Holders:Copyright © 2017 Wiley
First Published:First published in European Journal of Heart Failure 19(9):1186-1197
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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