title: Efficacy of Sacubitril/Valsartan Relative to a Prior Decompensation: The PARADIGM-HF Trial.
abstract: This study assessed whether the benefit of sacubtril/valsartan therapy varied with clinical stability.
  
  
  
  Despite the benefit of sacubitril/valsartan therapy shown in the PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial, it has been suggested that switching from an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker should be delayed until occurrence of clinical decompensation.
  
  
  
  Outcomes were compared among patients who had prior hospitalization within 3 months of screening (n = 1,611 [19%]), between 3 and 6 months (n = 1,009 [12%]), between 6 and 12 months (n = 886 [11%]), >12 months (n = 1,746 [21%]), or who had never been hospitalized (n = 3,125 [37%]).
  
  
  
  Twenty percent of patients without prior HF hospitalization experienced a primary endpoint of cardiovascular death or heart failure (HF) hospitalization during the course of the trial. Despite the increased risk associated with more recent hospitalization, the efficacy of sacubitril/valsartan therapy did not differ from that of enalapril according to the occurrence of or time from hospitalization for HF before screening, with respect to the primary endpoint or with respect to cardiovascular or all-cause mortality.
  
  
  
  Patients with recent HF decompensation requiring hospitalization were more likely to experience cardiovascular death or HF hospitalization than those who had never been hospitalized. Patients who were clinically stable, as shown by a remote HF hospitalization (>3 months prior to screening) or by lack of any prior HF hospitalization, were as likely to benefit from sacubitril/valsartan therapy as more recently hospitalized patients. (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF]; NCT01035255).
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts. Electronic address: ssolomon@rics.bwh.harvard.edu.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Solomon
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Brian
authors.initials: B
authors.lastname: Claggett
authors.affiliation: Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, Texas.
authors.forename: Milton
authors.initials: M
authors.lastname: Packer
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Akshay
authors.initials: A
authors.lastname: Desai
authors.affiliation: Medical University of South Carolina and Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, South Carolina.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Zile
authors.affiliation: University of Gothenburg, Gothenburg, Sweden.
authors.forename: Karl
authors.initials: K
authors.lastname: Swedberg
authors.affiliation: University of Montreal, Montreal, Quebec, Canada.
authors.forename: Jean
authors.initials: J
authors.lastname: Rouleau
authors.affiliation: Novartis, East Hanover, New Jersey.
authors.forename: Victor
authors.initials: V
authors.lastname: Shi
authors.affiliation: Novartis, East Hanover, New Jersey.
authors.forename: Martin
authors.initials: M
authors.lastname: Lefkowitz
authors.affiliation: University of Glasgow, Glasgow, United Kingdom.
authors.forename: John J V
authors.initials: JJV
authors.lastname: McMurray
mesh_terms: D000368:Aged; D000613:Aminobutyrates / Q000627:therapeutic use*; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D002318:Cardiovascular Diseases / Q000401:mortality; D016022:Case-Control Studies; D018450:Disease Progression; D004311:Double-Blind Method; D004338:Drug Combinations; D057915:Drug Substitution; D004656:Enalapril / Q000627:therapeutic use; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D015260:Neprilysin / Q000037:antagonists & inhibitors; D013777:Tetrazoles / Q000627:therapeutic use*; D016896:Treatment Outcome; D000068756:Valsartan
chemical_list: D000613:Aminobutyrates; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001713:Biphenyl Compounds; D004338:Drug Combinations; D013777:Tetrazoles; D004656:Enalapril; D000068756:Valsartan; D015260:Neprilysin; C549068:sacubitril and valsartan sodium hydrate drug combination
keywords: heart failure; neprilysin inhibition; renin angiotensin system