Angiotensin-Neprilysin Inhibition and Renal Outcomes in Heart Failure With Preserved Ejection Fraction

Finnian R. Mc Causland*, Martin P. Lefkowitz, Brian Claggett, Nagesh S. Anavekar, Michele Senni, Mauro Gori, Pardeep S. Jhund, Martina M. McGrath, Milton Packer, Victor Shi, Dirk J. Van Veldhuisen, Faiez Zannad, Josep Comin-Colet, Marc A. Pfeffer, John J. V. McMurray, Scott D. Solomon

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)


Background: In patients with heart failure, chronic kidney disease is common and associated with a higher risk of renal events than in patients without chronic kidney disease. We assessed the renal effects of angiotensin/neprilysin inhibition in patients who have heart failure with preserved ejection fraction enrolled in the PARAGON-HF trial (Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction).

Methods: In this randomized, double-blind, event-driven trial, we assigned 4822 patients who had heart failure with preserved ejection fraction to receive sacubitril/valsartan (n=2419) or valsartan (n=2403). Herein, we present the results of the prespecified renal composite outcome (time to first occurrence of either: >= 50% reduction in estimated glomerular filtration rate (eGFR), end-stage renal disease, or death from renal causes), the individual components of this composite, and the influence of therapy on eGFR slope.

Results: At randomization, eGFR was 63 +/- 19 mL.min(-1).1.73 m(-2). At study closure, the composite renal outcome occurred in 33 patients (1.4%) assigned to sacubitril/valsartan and 64 patients (2.7%) assigned to valsartan (hazard ratio, 0.50 [95% CI, 0.33-0.77];P=0.001). The treatment effect on the composite renal end point did not differ according to the baseline eGFR (= 60 mL.min(-1).1.73 m(-2) (P-interaction=0.92). The decline in eGFR was less for sacubitril/valsartan than for valsartan (-2.0 [95% CI, -2.2 to -1.9] versus -2.7 [95% CI, -2.8 to -2.5] mL.min(-1).1.73 m(-2) per year).

Conclusions: In patients with heart failure with preserved ejection fraction, sacubitril/valsartan reduced the risk of renal events, and slowed decline in eGFR, in comparison with valsartan.

Registration: URL:; Unique identifier: NCT01920711.

Original languageEnglish
Pages (from-to)1236-1245
Number of pages10
Issue number13
Publication statusPublished - 29-Sep-2020


  • heart failure
  • renal insufficiency
  • chronic
  • treatment outcome
  • LCZ696

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