PMID- 23810881
OWN - NLM
STAT- MEDLINE
DCOM- 20131210
LR  - 20220309
IS  - 1558-3597 (Electronic)
IS  - 0735-1097 (Linking)
VI  - 62
IP  - 17
DP  - 2013 Oct 22
TI  - Safety and efficacy of eplerenone in patients at high risk for hyperkalemia 
      and/or worsening renal function: analyses of the EMPHASIS-HF study subgroups 
      (Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart 
      Failure).
PG  - 1585-93
LID - S0735-1097(13)02512-6 [pii]
LID - 10.1016/j.jacc.2013.04.086 [doi]
AB  - OBJECTIVES: The study sought to investigate the safety and efficacy of eplerenone 
      in patients at high risk for hyperkalemia or worsening renal function (WRF) in 
      EMPHASIS-HF, a trial that enrolled patients at least 55 years old with heart 
      failure and reduced ejection fraction (HF-REF), in New York Heart Association 
      (NYHA) functional class II and with an estimated glomerular filtration rate 
      (eGFR) >30 ml/min/1.73 m(2) and serum potassium <5.0 mmol/l. Patients were 
      receiving optimal therapy and most had been hospitalized for a cardiovascular 
      reason within 180 days of inclusion. BACKGROUND: Underuse of eplerenone in 
      patients with HF-REF may be due to fear of inducing hyperkalemia or WRF in 
      high-risk patients. METHODS: This was a pre-specified analysis of subgroups of 
      patients at high risk of hyperkalemia or WRF (patients >/= 75 years of age, with 
      diabetes, with eGFR <60 ml/min/1.73 m(2), and with systolic blood pressure < 
      median of 123 mm Hg), examining the major safety measures (potassium >5.5, >6.0, 
      and <3.5 mmol/l; hyperkalemia leading to study-drug discontinuation or 
      hospitalization; and hospitalization for WRF) as well as the primary outcome 
      (hospitalization for HF or cardiovascular mortality). RESULTS: In all high-risk 
      subgroups, patients treated with eplerenone had an increased risk of potassium 
      >5.5 mmol/l but not of potassium >6.0 mmol/l, and of hospitalization for 
      hyperkalemia or discontinuation of study medication due to adverse events. 
      Eplerenone was effective in reducing the primary composite endpoint in all 
      subgroups. CONCLUSIONS: In patients with chronic HF-REF, in NYHA functional class 
      II, and meeting specific inclusion and exclusion criteria, including an eGFR >30 
      ml/min/1.73 m(2) and potassium <5.0 mmol/l, eplerenone was both efficacious and 
      safe when carefully monitored, even in subgroups at high risk of developing 
      hyperkalemia or WRF. (A Comparison Of Outcomes In Patients In New York Heart 
      Association [NYHA] Class II Heart Failure When Treated With Eplerenone Or Placebo 
      In Addition To Standard Heart Failure Medicines [EMPHASIS-HF Study]; 
      NCT00232180).
CI  - Copyright (c) 2013 American College of Cardiology Foundation. Published by Elsevier 
      Inc. All rights reserved.
FAU - Eschalier, Romain
AU  - Eschalier R
AD  - Centre d'Investigation Clinique Inserm CIC-P 9501, Centre Hospitalier 
      Universitaire de Nancy, Nancy, France; Clermont University, Universite 
      d'Auvergne, UMR6284, and the Department of Cardiology, Clermont-Ferrand, France.
FAU - McMurray, John J V
AU  - McMurray JJ
FAU - Swedberg, Karl
AU  - Swedberg K
FAU - van Veldhuisen, Dirk J
AU  - van Veldhuisen DJ
FAU - Krum, Henry
AU  - Krum H
FAU - Pocock, Stuart J
AU  - Pocock SJ
FAU - Shi, Harry
AU  - Shi H
FAU - Vincent, John
AU  - Vincent J
FAU - Rossignol, Patrick
AU  - Rossignol P
FAU - Zannad, Faiez
AU  - Zannad F
FAU - Pitt, Bertram
AU  - Pitt B
CN  - EMPHASIS-HF Investigators
LA  - eng
SI  - ClinicalTrials.gov/NCT00232180
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20130627
PL  - United States
TA  - J Am Coll Cardiol
JT  - Journal of the American College of Cardiology
JID - 8301365
RN  - 0 (Mineralocorticoid Receptor Antagonists)
RN  - 27O7W4T232 (Spironolactone)
RN  - 6995V82D0B (Eplerenone)
SB  - IM
CIN - J Am Coll Cardiol. 2013 Oct 22;62(17):1594-5. PMID: 23810879
MH  - Aged
MH  - Aged, 80 and over
MH  - Eplerenone
MH  - Female
MH  - Heart Failure/blood/*drug therapy/mortality
MH  - Hospitalization/*trends
MH  - Humans
MH  - Hyperkalemia/blood/*chemically induced/mortality
MH  - Kidney Function Tests/trends
MH  - Male
MH  - Middle Aged
MH  - Mineralocorticoid Receptor Antagonists/adverse effects/*therapeutic use
MH  - Renal Insufficiency, Chronic/blood/*chemically induced/mortality
MH  - Risk Factors
MH  - Spironolactone/adverse effects/*analogs & derivatives/therapeutic use
MH  - Survival Rate/trends
MH  - Treatment Outcome
OTO - NOTNLM
OT  - ACE-I
OT  - ARB
OT  - BB
OT  - CI
OT  - CKD
OT  - DM
OT  - HF-REF
OT  - HR
OT  - MRA
OT  - SBP
OT  - WRF
OT  - angiotensin receptor blocker
OT  - angiotensin-converting enzyme inhibitor
OT  - beta-adrenergic receptor blocking agent
OT  - chronic kidney disease
OT  - confidence interval
OT  - diabetes
OT  - diabetes mellitus
OT  - eGFR
OT  - efficacy
OT  - elderly
OT  - eplerenone
OT  - estimated glomerular filtration rate
OT  - hazard ratio
OT  - heart failure with a reduced left ventricular ejection fraction
OT  - mineralocorticoid receptor antagonist
OT  - safety
OT  - systolic blood pressure
OT  - worsening renal function
EDAT- 2013/07/03 06:00
MHDA- 2013/12/16 06:00
CRDT- 2013/07/02 06:00
PHST- 2013/01/04 00:00 [received]
PHST- 2013/04/13 00:00 [revised]
PHST- 2013/04/15 00:00 [accepted]
PHST- 2013/07/02 06:00 [entrez]
PHST- 2013/07/03 06:00 [pubmed]
PHST- 2013/12/16 06:00 [medline]
AID - S0735-1097(13)02512-6 [pii]
AID - 10.1016/j.jacc.2013.04.086 [doi]
PST - ppublish
SO  - J Am Coll Cardiol. 2013 Oct 22;62(17):1585-93. doi: 10.1016/j.jacc.2013.04.086. 
      Epub 2013 Jun 27.