title: Comparative associations between angiotensin converting enzyme inhibitors, angiotensin receptor blockers and their combination, and outcomes in patients with heart failure and reduced ejection fraction.
abstract: BACKGROUND
  Angiotensin converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) are recommended in heart failure with reduced ejection fraction (HFREF), but there is limited data on ARB vs. ACE-I and their combination in unselected populations. The purpose of this study was to compare the associations between the use of ACE-I, ARB and their combination, and outcomes in HFREF.
  
  
  RESULTS
  We prospectively studied 22,947 patients with HFREF (ejection fraction<40%) enrolled in the Swedish Heart Failure Registry who received ACE-I but not ARB (n=15,801, 69%), ARB but not ACE-I (n=4335, 19%), their combination (n=571, 2%) or neither (n=2240, 10%). As compared with ACE-I alone, the hazard ratios (HRs) for ARB alone for all-cause mortality was 0.97 (95% CI=0.91-1.03; p=0.27), for HF hospitalization 1.08 (CI=1.02-1.15; p<0.01) and for the composite outcome 1.03 (CI=0.99-1.08; p=0.15). ACE-I and ARB combination had for death HR=0.98 (95% CI=0.84-1.14; p=0.76), for HF hospitalization HR=1.49 (CI=1.33-1.68; p<0.01) and for the composite outcome HR=1.35 (CI=1.21-1.50; p<0.01). Use of neither ACE-I nor ARB was associated with HR for death 1.41 (CI=1.33-1.50; p<0.01), for HF hospitalization 1.16 (CI=1.08-1.25; p<0.01) and for the composite outcome 1.28 (CI=1.21-1.35; p<0.01).
  
  
  CONCLUSIONS
  This large generalizable analysis confirms the current recommendation of using ACE-I as first choice in HFREF. ARB can be considered an alternative in patients who cannot use ACE-I but should not routinely replace ACE-I. The combination of ACE-I and ARB was not associated with additional benefit over either one alone, and may potentially be harmful.
authors.affiliation: Karolinska Institute, Department of Medicine, Cardiology Unit, Stockholm, Sweden; Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy. Electronic address: gianluigi.savarese@gmail.com.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Savarese
authors.affiliation: Karolinska Institute, Department of Medicine, Cardiology Unit, Stockholm, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Edner
authors.affiliation: Department of Cardiology and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Dahlström
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Perrone-Filardi
authors.affiliation: Karolinska Institute, Department of Medicine, Cardiology Unit, Stockholm, Sweden.
authors.forename: Camilla
authors.initials: C
authors.lastname: Hage
authors.affiliation: Karolinska Institute, Department of Medicine, Cardiology Unit, Stockholm, Sweden.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cosentino
authors.affiliation: Karolinska Institute, Department of Medicine, Cardiology Unit, Stockholm, Sweden.
authors.forename: Lars H
authors.initials: LH
authors.lastname: Lund
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D013318:Stroke Volume / Q000187:drug effects; D013548:Sweden / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors
keywords: Angiotensin converting enzyme inhibitors; Angiotensin receptor blockers; Heart failure with reduced ejection fraction; Prognosis; Registry