title: Independence of the blood pressure lowering effect and efficacy of the angiotensin receptor neprilysin inhibitor, LCZ696, in patients with heart failure with preserved ejection fraction: an analysis of the PARAMOUNT trial.
abstract: OBJECTIVE
  The first in class angiotensin receptor neprilysin inhibitor, LCZ696 has been shown to reduce levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), reduce left atrial size and improve New York Heart Association (NYHA) class in patients with heart failure with preserved ejection fraction (HFpEF). We examined whether the effects of LCZ696 were independent of systolic blood pressure (SBP) lowering.
  
  
  RESULTS
  In the Prospective comparison of ARNi (angiotensin receptor neprilysin inhibitor) with ARB (angiotensin receptor blocker) on Management Of heart failUre with preserved ejectioN fracTion (PARAMOUNT) trial 301 patients were randomly assigned to LCZ696 or valsartan. We examined the relationship between SBP lowering and LCZ696 on NT-proBNP level, left atrial size, NYHA class and estimated glomerular filtration rate (eGFR). By 12 weeks blood pressure was reduced by 9 mmHg (SD 15)/5 mmHg (SD 11) in patients receiving LCZ696 in comparison with 3 mmHg (SD 17)/2 mmHg (SD 12) in those receiving valsartan. The change in NT-proBNP was poorly correlated with change in SBP (LCZ696, r = 0.17, P = 0.06; valsartan, r = 0.05, P = 0.58) After adjustment for change in SBP, the ratio of change in NT-proBNP at 12 weeks for LCZ696 vs. valsartan was 0.76 (95% CI 0.63-0.93, P = 0.008), and similar to the ratio not adjusting for SBP (0.76, 95% CI 0.63-0.92, P = 0.006); P for interaction was 0.38). Similarly, reduction in left atrial volume index at 36 weeks, improvement in NYHA class and eGFR were all independent of the change in SBP.
  
  
  CONCLUSIONS
  In patients with HFpEF, the effect of the angiotensin receptor neprilysin inhibitor LCZ696 on NT-proBNP, left atrial volume, functional class, and eGFR was independent of reduction in SBP.
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA; BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Pardeep S
authors.initials: PS
authors.lastname: Jhund
authors.forename: Brian
authors.initials: B
authors.lastname: Claggett
authors.forename: Milton
authors.initials: M
authors.lastname: Packer
authors.forename: Michael R
authors.initials: MR
authors.lastname: Zile
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
authors.forename: Burkert
authors.initials: B
authors.lastname: Pieske
authors.forename: Martin
authors.initials: M
authors.lastname: Lefkowitz
authors.forename: Victor
authors.initials: V
authors.lastname: Shi
authors.forename: Toni
authors.initials: T
authors.lastname: Bransford
authors.forename: John J V
authors.initials: JJ
authors.lastname: McMurray
authors.forename: Scott D
authors.initials: SD
authors.lastname: Solomon
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000613:Aminobutyrates / Q000627:therapeutic use*; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects*; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D005919:Glomerular Filtration Rate; D006325:Heart Atria; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood; D015260:Neprilysin / Q000037:antagonists & inhibitors; D010446:Peptide Fragments / Q000097:blood; D011446:Prospective Studies; D013318:Stroke Volume; D013777:Tetrazoles / Q000627:therapeutic use*; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068756:Valsartan
chemical_list: D000613:Aminobutyrates; D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D004338:Drug Combinations; D010446:Peptide Fragments; D013777:Tetrazoles; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D000068756:Valsartan; D015260:Neprilysin; D014633:Valine; C549068:sacubitril and valsartan sodium hydrate drug combination
keywords: Blood pressure; Heart failure; NT-proBNP; Neprilysin inhibitor; Preserved ejection fraction