Time to clinical benefit of eplerenone among patients with heart failure and reduced ejection fraction: a subgroups analysis from EMPHASIS-HF trial

Monzo, L., Girerd, N., Duarte, K., Ferreira, J. P., McMurray, J. J.V. , van Veldhuisen, D. J., Swedberg, K., Pocock, S. J., Pitt, B. and Zannad, F. (2023) Time to clinical benefit of eplerenone among patients with heart failure and reduced ejection fraction: a subgroups analysis from EMPHASIS-HF trial. European Journal of Heart Failure, 25(8), pp. 1444-1449. (doi: 10.1002/ejhf.2952) (PMID:37370197)

Abstract

Aim: Eplerenone reduces the risk of cardiovascular death or first hospitalization for heart failure (HF) in patients with HF and a reduced ejection fraction (HFrEF), but it is still frequently underused in routine practice. We evaluated the time course of benefits of eplerenone after its initiation in HFrEF patients from EMPHASIS-HF trial. Methods and results: The EMPHASIS-HF trial was a double-blind randomized clinical trial assessing the effect of eplerenone in patients (N=2737, age 68.6±7.6 years, 22.3% women) with HFrEF and mild symptoms. The time trajectories for the effect of eplerenone vs. placebo on the primary composite end point (cardiovascular death or first hospitalization for HF) were investigated using Cox proportional hazards models with truncated data at each day post-randomization. Significant statistical reduction in the primary composite endpoint was observed 26 days after randomization (HR, 0.58; 95% CI, 0.34-1.00). Eplerenone was first associated with a significant reduction in the primary endpoint in 35 days or less in most subgroups, including patients with HF history ≥ 18 months (day 24), glomerular filtration rate < 60 ml/min (day 12), ischemic HF aetiology (day 28), age ≥ 65 (day 28), narrow QRS (day 30), higher MAGGIC score (day 35), lower potassium (day 30), left ventricular ejection fraction ≥ 30% (day 28) or already treated with betablockers (day 25). Conclusions: Eplerenone provides statistically significant and clinically meaningful benefits shortly after treatment initiation in most patients, irrespective of clinical profile. This result reinforces the need for an early initiation of eplerenone in HFrEF, as part of rapidly instituting guideline directed medical therapy.

• Item Type: Articles
• Additional Information: The EMPHASIS-HF trial was supported by Pfizer.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Ferreira, Mr Joao Pedro and McMurray, Professor John
• Authors: Monzo, L., Girerd, N., Duarte, K., Ferreira, J. P., McMurray, J. J.V., van Veldhuisen, D. J., Swedberg, K., Pocock, S. J., 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
• Publisher: Wiley
• ISSN: 1388-9842
• ISSN (Online): 1879-0844
• Published Online: 27 June 2023
• Copyright Holders: Copyright © 2023 European Society of Cardiology
• First Published: First published in European Journal of Heart Failure 25(8):1444-1449
• Publisher Policy: Reproduced in accordance with the publisher copyright policy