title: Prognostic Implications of Changes in N-Terminal Pro-B-Type Natriuretic Peptide in Patients With Heart Failure.
abstract: BACKGROUND
  Natriuretic peptides (NP) have prognostic value in heart failure (HF), although the clinical importance of changes in NP from baseline is unclear.
  
  
  OBJECTIVE
  The authors assessed whether a reduction in N-terminal pro-B-type NP (NT-proBNP) was associated with a decrease in HF hospitalization and cardiovascular mortality (primary endpoint) in patients with HF and reduced ejection fraction, whether treatment with sacubitril/valsartan reduced NT-proBNP below specific partition values more than enalapril, and whether the relationship between changes in NT-proBNP and changes in the primary endpoint were dependent on assigned treatment.
  
  
  METHODS
  In PARADIGM-HF (Prospective Comparison of ARNI [Angiotensin Receptor-Neprilysin Inhibitor] with ACEI [Angiotensin-Converting-Enzyme Inhibitor] to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial), baseline NT-proBNP was measured in 2,080 patients; 1,292 had baseline values >1,000 pg/ml and were reassessed at 1 and 8 months. We related change in NT-proBNP to outcomes.
  
  
  RESULTS
  One month after randomization, 24% of the baseline NT-proBNP levels >1,000 pg/ml had fallen to ≤1,000 pg/ml. Risk of the primary endpoint was 59% lower in patients with a fall in NT-proBNP to ≤1,000 pg/ml than in those without such a fall. In sacubitril/valsartan-treated patients, median NT-proBNP was significantly lower 1 month after randomization than in enalapril-treated patients, and it fell to ≤1,000 pg/ml in 31% versus 17% of patients treated with sacubitril/valsartan and enalapril, respectively. There was no significant interaction between treatment and the relationship between change in NT-proBNP and the subsequent risk of the primary endpoint.
  
  
  CONCLUSIONS
  Patients who attained a significant reduction in NT-proBNP had a lower subsequent rate of cardiovascular death or HF hospitalization independent of the treatment group. Treatment with sacubitril/valsartan was nearly twice as likely as enalapril to reduce NT-proBNP to values ≤1,000 pg/ml. (Prospective Comparison of ARNI [Angiotensin Receptor-Neprilysin Inhibitor] with ACEI [Angiotensin-Converting-Enzyme Inhibitor] to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial) [PARADIGM-HF]; NCT01035255.).
authors.affiliation: Medical University of South Carolina and Ralph H. Johnson Veterans Administration Medical Center, Charleston, South Carolina. Electronic address: zilem@musc.edu.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Zile
authors.affiliation: Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Claggett
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
authors.forename: Margaret F
authors.initials: MF
authors.lastname: Prescott
authors.affiliation: University of Glasgow, Glasgow, United Kingdom.
authors.forename: John J V
authors.initials: JJ
authors.lastname: McMurray
authors.affiliation: Baylor University Medical Center, Dallas, Texas.
authors.forename: Milton
authors.initials: M
authors.lastname: Packer
authors.affiliation: Montreal Heart Institute and University of Montreal, Montreal, Quebec, Canada.
authors.forename: Jean L
authors.initials: JL
authors.lastname: Rouleau
authors.affiliation: University of Gothenburg, Gothenburg, Sweden.
authors.forename: Karl
authors.initials: K
authors.lastname: Swedberg
authors.affiliation: Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Akshay S
authors.initials: AS
authors.lastname: Desai
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
authors.forename: Jianjian
authors.initials: J
authors.lastname: Gong
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
authors.forename: Victor C
authors.initials: VC
authors.lastname: Shi
authors.affiliation: Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Solomon
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D015415:Biomarkers / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011379:Prognosis; D011446:Prospective Studies; D016037:Single-Blind Method; D013318:Stroke Volume; D016896:Treatment Outcome; D000068756:Valsartan / Q000008:administration & dosage*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D004656:Enalapril; D000068756:Valsartan
keywords: biomarker; chronic heart failure; natriuretic peptide; reduced ejection fraction