ARNI reduces renal outcomes in patients with HFmrEF/HFpEF

Renal Outcomes in PARAGLIDE-HF and PARAGON-HF

News - Aug. 26, 2023

Presented at the ESC Congress 2023 by: Muthiah Vaduganathan, MD - Boston, MA, USA

Introduction and methods

The aim of this study was to investigate the effects of sacubitril/valsartan on renal outcomes in patients with HFmrEF/HFpEF of the PARAGLIDE-HF and PARAGON-HF trials.

This was a pre-specified participant-level pooled analysis of the PARAGLIDE-HF and PARAGON-HF trials (n=5262 participants). The renal outcomes were: the renal composite outcome, which was time to first ≥50% decline in eGFR from baseline, ESRD, or renal death; and the slope of serial eGFR measurements.

Both PARAGLIDE-HF (n=466) and PARAGON-HF (n=4796) evaluated the effects of sacubitril/valsartan in patients with HFmrEF or HFpEF. However, a higher risk patient population was included in the PARAGLIDE-HF trial (patients were enrolled within 30 days after worsening HF), whereas the patient population was more clinically stable in PARAGON-HF (where a sequential run-in period with treatment of valsartan and sacubitril/valsartan was included before randomization). The median follow-up period was 0.4 years in PARAGLIDE-HF and 2.9 years in PARAGON-HF.

Main results

  • Sacubitril/valsartan reduced the risk of the renal composite outcome compared with valsartan (HR: 0.60; 95%CI: 0.44-0.83; P=0.002). A statistical significant difference between the treatment groups was seen within 2 months after study randomization (at day 58). Beneficial effects with sacubitril/valsartan were seen in all three components of the composite outcome.
  • The effect of sacubitril/valsartan on the renal composite outcome was consistent in various subgroups, which included the different patient populations of the different trials, LVEF >60% or<60%, or eGFR ≥60mL/min/1.73m² or <60mL/min/1.73m².
  • Sacubitril/valsartan reduced the decline in eGFR over time compared with valsartan in patients of both trials (in the PARAGON-HF trial, between arm difference = 0.6 mL/min/1.73m²; 95%CI: 0.3-0.8; P<0.001; and in the PARAGLIDE-HF trial, between arm difference = 4.2 mL/min/1.73m²; 95%CI: 0.4-8.0; P=0.030).


This pooled analyses of the PARAGLIDE-HF and the PARAGON-HF trials demonstrated that sacubitril/valsartan compared with valsartan reduces the risk of clinically relevant renal events in patients with HFmrEF/HFpEF. This beneficial effect was seen in both high-risk patients hospitalized for acute HF as well as in patients in ambulatory care. The effects of sacubitril/valsartan on renal outcomes were seen within months after treatment initiation. Moreover, sacubitril/valsartan slowed the eGFR decline over time compared with valsartan.

- Our reporting is based on the information provided at the ESC Congress 2023 -

Watch the video with Muthiah Vaduganathan about this analysis

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