title: The impact of eplerenone at different levels of risk in patients with systolic heart failure and mild symptoms: insight from a novel risk score for prognosis derived from the EMPHASIS-HF trial.
abstract: OBJECTIVE
  Our objective was to create a simple prognostic risk score for patients with systolic heart failure and mild symptoms. We then assessed the efficacy of eplerenone across different categories of risk.
  
  
  RESULTS
  The Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure trial (EMPHASIS-HF) was an international randomized trial, comparing eplerenone with placebo in 2737 patients with systolic heart failure and mild symptoms. The primary outcome was a composite of cardiovascular death or hospitalization for heart failure, over a median 2.1 years follow-up. Using multivariable Cox modelling age, sex, systolic blood pressure, estimated glomerular filtration rate, diabetes, BMI, haemoglobin, prior heart failure (HF) hospitalization, prior myocardial infarction/coronary artery bypass surgery (CABG), and heart rate were identified as strong independent risk factors. Estimates from the model were converted into a simple integer risk score which was categorized into three groups of low-, medium-, and high risk. In placebo patients, the rates (per 100 patient-years) for the primary outcome were 7.6, 19.0, and 39.4 in the low-, medium-, and high-risk groups, respectively. On eplerenone, these rates were reduced to 5.6, 12.2, and 24.2, respectively. Eplerenone was beneficial across all risk categories and the hazard ratios were similar. The absolute treatment benefit was greatest among those at highest risk. Similar patterns emerged for all-cause mortality and for all HF hospitalizations.
  
  
  CONCLUSIONS
  This easy-to-use integer risk score should be of value in quantifying individual patient risk in patients with systolic HF and mild symptoms. The relative benefits of eplerenone appeared consistent across the whole spectrum of risk, including those at lower risk.
authors.affiliation: Department of Medical Statistics, London School of Hygiene & Tropical Medicine, London, UK.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Collier
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Pocock
authors.forename: John J V
authors.initials: JJ
authors.lastname: McMurray
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
authors.forename: Henry
authors.initials: H
authors.lastname: Krum
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
authors.forename: Karl
authors.initials: K
authors.lastname: Swedberg
authors.forename: Harry
authors.initials: H
authors.lastname: Shi
authors.forename: John
authors.initials: J
authors.lastname: Vincent
authors.forename: Bertram
authors.initials: B
authors.lastname: Pitt
mesh_terms: D000328:Adult; D000368:Aged; D016757:Death, Sudden, Cardiac / Q000209:etiology; D000077545:Eplerenone; D005260:Female; D054143:Heart Failure, Systolic / Q000188:drug therapy* / Q000401:mortality; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone
keywords: Heart failure; Prognosis; Risk score