PMID- 28303624
OWN - NLM
STAT- MEDLINE
DCOM- 20180522
LR  - 20180601
IS  - 1879-0844 (Electronic)
IS  - 1388-9842 (Linking)
VI  - 19
IP  - 9
DP  - 2017 Sep
TI  - Effect of eplerenone in patients with heart failure and reduced ejection
      fraction: potential effect modification by abdominal obesity. Insight from the
      EMPHASIS-HF trial.
PG  - 1186-1197
LID - 10.1002/ejhf.792 [doi]
AB  - 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.
CI  - (c) 2017 The Authors. European Journal of Heart Failure (c) 2017 European Society
      of Cardiology.
FAU - Olivier, Arnaud
AU  - Olivier A
AD  - Inserm CIC Plurithematique 1433, UMRS 1116 Inserm, CHRU Nancy,
      Vandoeuvre-les-Nancy, France.
AD  - Cardiovascular Department, CHRU Nancy, Vandoeuvre-les-Nancy, France.
AD  - F-CRIN INI-CRCT, France.
FAU - Pitt, Bertram
AU  - Pitt B
AD  - University of Michigan, School of Medicine, Ann Arbor, MI, USA.
FAU - Girerd, Nicolas
AU  - Girerd N
AD  - Inserm CIC Plurithematique 1433, UMRS 1116 Inserm, CHRU Nancy,
      Vandoeuvre-les-Nancy, France.
AD  - F-CRIN INI-CRCT, France.
AD  - Universite de Lorraine, Nancy, France.
AD  - Federation de Recherche 3209, Vandoeuvre-les-Nancy, France.
FAU - Lamiral, Zohra
AU  - Lamiral Z
AD  - Inserm CIC Plurithematique 1433, UMRS 1116 Inserm, CHRU Nancy,
      Vandoeuvre-les-Nancy, France.
AD  - F-CRIN INI-CRCT, France.
FAU - Machu, Jean-Loup
AU  - Machu JL
AD  - Inserm CIC Plurithematique 1433, UMRS 1116 Inserm, CHRU Nancy,
      Vandoeuvre-les-Nancy, France.
AD  - F-CRIN INI-CRCT, France.
FAU - McMurray, John J V
AU  - McMurray JJV
AD  - University of Glasgow, Glasgow, UK.
FAU - Swedberg, Karl
AU  - Swedberg K
AD  - University of Gothenburg, Gothenburg, Sweden.
FAU - van Veldhuisen, Dirk J
AU  - van Veldhuisen DJ
AD  - University Medical Center, Groningen, the Netherlands.
FAU - Collier, Timothy J
AU  - Collier TJ
AD  - London School of Hygiene and Tropical Medicine, London, UK.
FAU - Pocock, Stuart J
AU  - Pocock SJ
AD  - London School of Hygiene and Tropical Medicine, London, UK.
FAU - Rossignol, Patrick
AU  - Rossignol P
AD  - Inserm CIC Plurithematique 1433, UMRS 1116 Inserm, CHRU Nancy,
      Vandoeuvre-les-Nancy, France.
AD  - F-CRIN INI-CRCT, France.
AD  - Universite de Lorraine, Nancy, France.
AD  - Federation de Recherche 3209, Vandoeuvre-les-Nancy, France.
FAU - Zannad, Faiez
AU  - Zannad F
AD  - Inserm CIC Plurithematique 1433, UMRS 1116 Inserm, CHRU Nancy,
      Vandoeuvre-les-Nancy, France.
AD  - Cardiovascular Department, CHRU Nancy, Vandoeuvre-les-Nancy, France.
AD  - F-CRIN INI-CRCT, France.
AD  - Universite de Lorraine, Nancy, France.
AD  - Federation de Recherche 3209, Vandoeuvre-les-Nancy, France.
FAU - Pizard, Anne
AU  - Pizard A
AD  - Inserm CIC Plurithematique 1433, UMRS 1116 Inserm, CHRU Nancy,
      Vandoeuvre-les-Nancy, France.
AD  - F-CRIN INI-CRCT, France.
AD  - Universite de Lorraine, Nancy, France.
AD  - Federation de Recherche 3209, Vandoeuvre-les-Nancy, France.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20170316
PL  - England
TA  - Eur J Heart Fail
JT  - European journal of heart failure
JID - 100887595
RN  - 0 (Mineralocorticoid Receptor Antagonists)
RN  - 27O7W4T232 (Spironolactone)
RN  - 4964P6T9RB (Aldosterone)
RN  - 6995V82D0B (eplerenone)
SB  - IM
CIN - Eur J Heart Fail. 2017 Sep;19(9):1198-1200. PMID: 28560824
MH  - Aged
MH  - Aldosterone/metabolism
MH  - Drug Monitoring/methods
MH  - Female
MH  - *Heart Failure, Systolic/complications/diagnosis/drug therapy/metabolism
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Mineralocorticoid Receptor Antagonists/administration & dosage/adverse effects
MH  - *Obesity, Abdominal/complications/diagnosis/metabolism
MH  - Spironolactone/administration & dosage/adverse effects/*analogs & derivatives
MH  - Stroke Volume
MH  - Treatment Outcome
MH  - *Ventricular Dysfunction, Left/diagnosis/metabolism/mortality
OTO - NOTNLM
OT  - *Abdominal obesity
OT  - *Eplerenone
OT  - *Heart failure with reduced ejection fraction
EDAT- 2017/03/18 06:00
MHDA- 2018/05/23 06:00
CRDT- 2017/03/18 06:00
PHST- 2016/05/12 00:00 [received]
PHST- 2017/01/17 00:00 [revised]
PHST- 2017/01/24 00:00 [accepted]
PHST- 2017/03/18 06:00 [pubmed]
PHST- 2018/05/23 06:00 [medline]
PHST- 2017/03/18 06:00 [entrez]
AID - 10.1002/ejhf.792 [doi]
PST - ppublish
SO  - Eur J Heart Fail. 2017 Sep;19(9):1186-1197. doi: 10.1002/ejhf.792. Epub 2017 Mar 
      16.