title: Aspirin does not reduce the clinical benefits of the mineralocorticoid receptor antagonist eplerenone in patients with systolic heart failure and mild symptoms: an analysis of the EMPHASIS-HF study.
abstract: It is not known whether concomitant use of aspirin might attenuate the beneficial effects of mineralocorticoid receptor antagonists (MRAs). The purpose of this subgroup analysis was to explore the interaction between baseline aspirin treatment and the effect of eplerenone on the primary efficacy outcomes (composite of hospitalization for heart failure or cardiovascular mortality), its components, and safety markers [estimated glomerular filtration rate (eGFR), systolic blood pressure (SBP), and serum potassium >5.5 mmol/L] in the Eplerenone in Mild Patients Hospitalization and SurvIval Study in Heart Failure trial (EMPHASIS-HF).
  
  
  
  Patients with chronic heart failure, reduced ejection fraction (HFREF), and mild symptoms were enrolled in EMPHASIS-HF. We evaluated baseline characteristics according to aspirin use. We explored the interaction between aspirin and eplerenone, using Cox proportional hazards models providing adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) and P-values for interaction. Of the 2737 patients randomized, 1605 patients (58.6%) were taking aspirin. The beneficial effects of eplerenone on the primary endpoint were similar in patients not treated (adjusted HR 0.59, 95% CI 0.46-0.75) or treated (adjusted HR 0.71, 95% CI 0.59-0.87) with aspirin at baseline (interaction P-value = 0.19). We did not observe any significant modification of the safety markers by aspirin that was clinically meaningful.
  
  
  
  Aspirin use in patients with chronic systolic heart failure and mild symptoms did not substantially reduce the overall beneficial effects of the MRA eplerenone contrary to what has been described in some studies with ACE inhibitors.
authors.affiliation: Centre of Cardiovascular Research & Education in Therapeutics, Department of Epidemiology & Preventive Medicine, Monash University, Melbourne, Australia.
authors.forename: Ken Lee
authors.initials: KL
authors.lastname: Chin
authors.affiliation: London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Collier
authors.affiliation: University of Michigan School of Medicine, Ann Arbor, MI, USA.
authors.forename: Bertram
authors.initials: B
authors.lastname: Pitt
authors.affiliation: British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
authors.forename: John J V
authors.initials: JJ
authors.lastname: McMurray
authors.affiliation: Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.|National Heart and Lung Institute, Imperial College, London, UK.
authors.forename: Karl
authors.initials: K
authors.lastname: Swedberg
authors.affiliation: University of Groningen, 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: Stuart J
authors.initials: SJ
authors.lastname: Pocock
authors.affiliation: Pfizer, New York, USA.
authors.forename: John
authors.initials: J
authors.lastname: Vincent
authors.affiliation: Pfizer, New York, USA.
authors.forename: Eva
authors.initials: E
authors.lastname: Turgonyi
authors.affiliation: CHU and University Henri Poincaré, Nancy, France.
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
authors.affiliation: Centre of Cardiovascular Research & Education in Therapeutics, Department of Epidemiology & Preventive Medicine, Monash University, Melbourne, Australia.
authors.forename: Henry
authors.initials: H
authors.lastname: Krum
mesh_terms: D000368:Aged; D001241:Aspirin / Q000627:therapeutic use*; D001794:Blood Pressure; D002908:Chronic Disease; D004347:Drug Interactions; D000077545:Eplerenone; D005260:Female; D005919:Glomerular Filtration Rate; D054143:Heart Failure, Systolic / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011188:Potassium / Q000097:blood; D016016:Proportional Hazards Models; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013318:Stroke Volume
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D010975:Platelet Aggregation Inhibitors; D013148:Spironolactone; D000077545:Eplerenone; D001241:Aspirin; D011188:Potassium
keywords: Aldosterone; Aspirin; Bradykinin; Eplerenone; Heart failure