title: Clinical benefit of eplerenone in patients with mild symptoms of systolic heart failure already receiving optimal best practice background drug therapy: analysis of the EMPHASIS-HF study.
abstract: BACKGROUND
  In EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure), eplerenone significantly reduced major cardiovascular events versus placebo in 2737 patients with mild symptoms of heart failure and an ejection fraction of <35%, in addition to recommended therapy. However, it is not known whether such benefits were preserved in patients receiving optimal background drug therapy, that is, high doses of angiotensin-converting enzyme inhibitor (ACEi, or angiotensin receptor blocker), β-blocker, or both drug classes.
  
  
  RESULTS
  We further analyzed EMPHASIS-HF according to the use and dose of these background drug classes. Patients receiving ≥ 50% of target dose were considered to be receiving high doses; patients on <50% or no drug comprised the low-dose group. The primary end point of the study (cardiovascular death/heart failure hospitalization), as well as all-cause mortality, was evaluated in this way. The beneficial clinical effects of eplerenone (as observed in the main study) were preserved for the EMPHASIS-HF primary end point in patients receiving higher doses of ACEi or angiotensin receptor blocker, β-blocker, or both (hazard ratio for eplerenone versus placebo, ACEi/angiotensin receptor blocker: high dose, 0.67; low dose, 0.65; β-blockers: high dose, 0.55; low dose, 0.72; both ACEi/angiotensin receptor blocker and β-blocker: high dose, 0.59; low dose, 0.68; P value for interaction 0.80, 0.15, and 0.53, respectively), as well as for all-cause mortality. There were no major safety issues, except a borderline increased risk of hypotension with eplerenone in those on high-dose ACEi or ACEi/β-blocker.
  
  
  CONCLUSIONS
  Eplerenone provides substantial benefit on major events (with an acceptable safety profile) in patients with mild symptoms of systolic heart failure, even in those already receiving high doses of standard background therapies.
authors.affiliation: CCRE Therapeutics, Monash University, Melbourne, Australia. henry.krum@monash.edu
authors.forename: Henry
authors.initials: H
authors.lastname: Krum
authors.forename: Harry
authors.initials: H
authors.lastname: Shi
authors.forename: Bertram
authors.initials: B
authors.lastname: Pitt
authors.forename: John
authors.initials: J
authors.lastname: McMurray
authors.forename: Karl
authors.initials: K
authors.lastname: Swedberg
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
authors.forename: John
authors.initials: J
authors.lastname: Vincent
authors.forename: Stuart
authors.initials: S
authors.lastname: Pocock
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
mesh_terms: D018674:Adrenergic Antagonists / Q000008:administration & dosage*; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D019985:Benchmarking; D004359:Drug Therapy, Combination; D000077545:Eplerenone; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D018674:Adrenergic Antagonists; D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone
keywords: ACE inhibitor; aldosterone; angiotensin receptor blocker; eplerenone; heart failure; β-blocker