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Abstract: FR-OR132

Effect of Angiotensin-Neprilysin Inhibition on Renal Outcomes in Heart Failure with Preserved Ejection Fraction

Session Information

  • High-Impact Clinical Trials
    November 08, 2019 | Location: Ballroom C, Walter E. Washington Convention Center
    Abstract Time: 02:15 PM - 02:30 PM

Category: Hypertension and CVD

  • No subcategory defined


  • McCausland, Finnian R., Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Claggett, Brian, Harvard Medical School, Boston, Massachusetts, United States
  • Anavekar, Nagesh, University of Melbourne, Melbourne, Victoria, Australia
  • Gori, Mauro, ASST Papa Giovanni XXIII Bergamo, Bergamo, Italy
  • Jhund, Pardeep, University of Glasgow, Glasgow, United Kingdom
  • Lefkowitz, Martin P., Novartis, East Hanover, New Jersey, United States
  • McGrath, Martina M., Harvard University, Chestnut Hill, Massachusetts, United States
  • McMurray, John, University of Glasgow, Glasgow, United Kingdom
  • Pfeffer, Marc A., Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Shi, Victor, Novartis, East Hanover, New Jersey, United States
  • Van veldhuisen, Dirk J., UMC Groningen, Groningen, Netherlands
  • Zannad, Faiez, Inserm, CHU & Université de Lorraine, Vandoeuvre les Nancy, France
  • Solomon, Scott D., Brigham and Women's Hospital, Boston, Massachusetts, United States

Chronic Kidney Disease (CKD) confers an increased risk of cardiovascular (CV) and renal events in patients with heart failure and preserved left ventricular ejection fraction (HFpEF). We assessed the long-term renal effects of angiotensin/neprilysin inhibition, a prespecified secondary outcome, in patients with HFpEF enrolled in the PARAGON-HF trial.


In this randomized, double-blind, parallel group, active controlled, event-driven trial, we assigned 4,822 patients with chronic HFpEF to receive sacubitril/valsartan or valsartan. Key exclusion criteria included a baseline eGFR <30mL/min/1.73m2. The prespecified renal outcome, a key secondary endpoint, was the time to first occurrence of either a ≥50% reduction in eGFR relative to baseline, attainment of end-stage renal disease, or renal death. We also evaluated the effect of treatment on the change in eGFR during follow up, and the influence of eGFR on the efficacy of sacubitril/valsartan for reducing the primary composite outcome.


The mean age was 73±8 years; 52% were female. At baseline, mean (+/- SD) eGFR was 63±19 mL/min/1.73m2; 2,341 participants (49%) had CKD (eGFR <60 mL/min/1.73m2) and 43% had diabetes. At study closure, the composite renal outcome had occurred in significantly fewer patients in the sacubitril/valsartan group compared with the valsartan group (HR 0.50, 95% CI 0.33, 0.77, p = 0.002), and the mean decline in eGFR during follow up was less for the sacubitril/valsartan group (full results will be available for the ASN annual meeting). Patients with lower eGFR derived greater benefit from sacubitril/valsartan for reducing the primary composite outcome of total heart failure hospitalization or CV death.


In patients with chronic HFpEF, sacubitril/valsartan reduced the risk of clinically important renal events, and slowed the progression of kidney disease, compared with valsartan. (Funded by Novartis; PARAGON-HF number, NCT01920711.)


  • Commercial Support – Novartis