Renal effects of the angiotensin receptor neprilysin inhibitor LCZ696 in patients with heart failure and preserved ejection fraction

Eur J Heart Fail. 2015 May;17(5):510-7. doi: 10.1002/ejhf.232. Epub 2015 Feb 6.

Abstract

Background: Increases in serum creatinine with renin-angiotensin-aldosterone system (RAAS) inhibitors can lead to unnecessary discontinuation of these agents. The dual-acting angiotensin receptor neprilysin inhibitor LCZ696 improves clinical outcome patients with heart failure with reduced ejection fraction, and pilot data suggest potential benefit in heart failure with preserved ejection fraction (HFpEF). The effects of LCZ696 on renal function have not been assessed.

Methods and results: A total of 301 HFpEF patients were randomly assigned to LCZ696 or valsartan in the PARAMOUNT trial. We studied renal function [creatinine, estimated glomerular filtration rate (eGFR), cystatin C, and urinary albumin to creatinine ratio (UACR)] at baseline, 12 weeks, and after 36 weeks of treatment. Worsening renal function (WRF) was determined as an serum creatinine increase of >0.3 mg/dL and/or >25% between two time-points. Mean eGFR at baseline was 65.4 ± 20.4 mL/min per 1.73 m(2) . The eGFR declined less in the LCZ696 group than in the valsartan group (-1.5 vs. -5.2 mL/min per 1.73 m(2) ; P = 0.002). The incidence of WRF was lower in the LCZ696 group (12%) than in the valsartan group (18%) at any time-point, but this difference was not statistically significant (P = 0.18). Over 36 weeks, the geometric mean of UACR increased in the LCZ696 group (2.4-2.9 mg/mmol), whereas it remained stable in the valsartan group (2.1-2.0 mg/mmol; P for difference between groups = 0.016).

Conclusion: In patients with HFpEF, therapy with LCZ696 for 36 weeks was associated with preservation of eGFR compared with valsartan therapy, but an increase in UACR.

Keywords: Albumin excretion; Angiotensin receptor neprilysin inhibitor; LCZ696; Renal function.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aminobutyrates / therapeutic use*
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use
  • Angiotensin Receptor Antagonists / therapeutic use*
  • Creatinine / blood
  • Double-Blind Method
  • Female
  • Glomerular Filtration Rate
  • Heart Failure / drug therapy*
  • Heart Failure / physiopathology
  • Humans
  • Kidney / physiopathology*
  • Male
  • Middle Aged
  • Neprilysin / antagonists & inhibitors*
  • Stroke Volume*
  • Tetrazoles / therapeutic use*
  • Valsartan / therapeutic use

Substances

  • Aminobutyrates
  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin Receptor Antagonists
  • Tetrazoles
  • Valsartan
  • Creatinine
  • Neprilysin
  • sacubitril-valsartan