title: Effect of eplerenone in patients with heart failure and reduced ejection fraction: potential effect modification by abdominal obesity. Insight from the EMPHASIS-HF trial.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Inserm CIC Plurithématique 1433, UMRS 1116 Inserm, CHRU Nancy, Vandoeuvre-lès-Nancy, France.|Cardiovascular Department, CHRU Nancy, Vandoeuvre-lès-Nancy, France.|F-CRIN INI-CRCT, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Olivier
authors.affiliation: University of Michigan, School of Medicine, Ann Arbor, MI, USA.
authors.forename: Bertram
authors.initials: B
authors.lastname: Pitt
authors.affiliation: Inserm CIC Plurithématique 1433, UMRS 1116 Inserm, CHRU Nancy, Vandoeuvre-lès-Nancy, France.|F-CRIN INI-CRCT, France.|Université de Lorraine, Nancy, France.|Fédération de Recherche 3209, Vandoeuvre-lès-Nancy, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Girerd
authors.affiliation: Inserm CIC Plurithématique 1433, UMRS 1116 Inserm, CHRU Nancy, Vandoeuvre-lès-Nancy, France.|F-CRIN INI-CRCT, France.
authors.forename: Zohra
authors.initials: Z
authors.lastname: Lamiral
authors.affiliation: Inserm CIC Plurithématique 1433, UMRS 1116 Inserm, CHRU Nancy, Vandoeuvre-lès-Nancy, France.|F-CRIN INI-CRCT, France.
authors.forename: Jean-Loup
authors.initials: JL
authors.lastname: Machu
authors.affiliation: University of Glasgow, Glasgow, UK.
authors.forename: John J V
authors.initials: JJV
authors.lastname: McMurray
authors.affiliation: University of Gothenburg, Gothenburg, Sweden.
authors.forename: Karl
authors.initials: K
authors.lastname: Swedberg
authors.affiliation: University Medical Center, Groningen, the Netherlands.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
authors.affiliation: London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Collier
authors.affiliation: London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Pocock
authors.affiliation: Inserm CIC Plurithématique 1433, UMRS 1116 Inserm, CHRU Nancy, Vandoeuvre-lès-Nancy, France.|F-CRIN INI-CRCT, France.|Université de Lorraine, Nancy, France.|Fédération de Recherche 3209, Vandoeuvre-lès-Nancy, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Rossignol
authors.affiliation: Inserm CIC Plurithématique 1433, UMRS 1116 Inserm, CHRU Nancy, Vandoeuvre-lès-Nancy, France.|Cardiovascular Department, CHRU Nancy, Vandoeuvre-lès-Nancy, France.|F-CRIN INI-CRCT, France.|Université de Lorraine, Nancy, France.|Fédération de Recherche 3209, Vandoeuvre-lès-Nancy, France.
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
authors.affiliation: Inserm CIC Plurithématique 1433, UMRS 1116 Inserm, CHRU Nancy, Vandoeuvre-lès-Nancy, France.|F-CRIN INI-CRCT, France.|Université de Lorraine, Nancy, France.|Fédération de Recherche 3209, Vandoeuvre-lès-Nancy, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Pizard
mesh_terms: D000368:Aged; D000450:Aldosterone / Q000378:metabolism; D016903:Drug Monitoring / Q000379:methods; D000077545:Eplerenone; D005260:Female; D054143:Heart Failure, Systolic / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects; D056128:Obesity, Abdominal / Q000150:complications / Q000175:diagnosis / Q000378:metabolism; D013148:Spironolactone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013318:Stroke Volume; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000450:Aldosterone; D000077545:Eplerenone
keywords: Abdominal obesity; Eplerenone; Heart failure with reduced ejection fraction