Renal function stratified dose comparisons of eplerenone versus placebo in the EMPHASIS‐HF trial

Ferreira, J. P. et al. (2019) Renal function stratified dose comparisons of eplerenone versus placebo in the EMPHASIS‐HF trial. European Journal of Heart Failure, 21(3), pp. 345-351. (doi: 10.1002/ejhf.1400) (PMID:30768732)

182952.pdf - Accepted Version



Background: Current heart failure guidelines recommend target eplerenone dose of 50 mg/day. We have examined the effect of different eplerenone doses based on pre‐specified renal function stratification in the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS‐HF). Methods and results: In EMPHASIS‐HF, the target dose of eplerenone/placebo was stratified at randomization according to estimated glomerular filtration rate (eGFR): 50 mg/day if eGFR ≥ 50 mL/min/1.73 m2 and ≤ 25 mg/day if eGFR 30–49 mL/min/1.73 m2. Patients remained within these dose ranges during the trial (as per stratification). The primary outcome was a composite of heart failure hospitalization or cardiovascular mortality. Eplerenone was superior to placebo within each respective eGFR stratum [eplerenone vs. placebo in the eGFR ≥ 50 mL/min/1.73 m2 stratum: hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.45–0.74; and eplerenone vs. placebo in the eGFR 30–49 mL/min/1.73 m2 stratum: HR 0.62, 95% CI 0.49–0.78; Pinteraction = 0.89]. Despite receiving lower eplerenone doses, patients in the eGFR 30–49 mL/min/1.73 m2 stratum more often had hyperkalaemia, renal failure events, and drug discontinuation. Conclusion: In EMPHASIS‐HF the eplerenone dose was stratified according to renal function and the treatment effect was not influenced by renal function: 25 mg/day in patients with eGFR 30–49 mL/min/1.73 m2 was as effective as 50 mg/day in patients with eGFR > =50 mL/min/1.73 m2. However, patients with impaired renal function experienced more adverse events, despite reveiving lower eplerenone doses. Current guidelines do not recommend tailoring the dose of eplereone according to renal function but the current data suggest they should.

Item Type:Articles
Additional Information:Funding: The EMPHASIS‐HF study was sponsored by Pfizer.
Glasgow Author(s) Enlighten ID:McMurray, Professor John
Authors: Ferreira, J. P., Abreu, P., McMurray, J. J.V., van Veldhuisen, D. J., Swedberg, K., Pocock, S. J., Vincent, J., Lins, K., Rossignol, P., Pitt, B., and Zannad, F.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:European Journal of Heart Failure
ISSN (Online):1879-0844
Published Online:15 February 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in European Journal of Heart Failure 21(3);345-351
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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