Physicians' Academy for Cardiovascular Education

ARNI may reduce adverse kidney outcomes in HF patients

Angiotensin-neprilysin inhibition and renal outcomes across the spectrum of ejection fraction in heart failure

Literature - Mc Causland FR, Lefkowitz MP, Claggett B et al., - Eur J Heart Fail 2022, doi: 10.1002/ejhf.2421

Introduction and methods


Use of angiotensin-converting enzyme inhibitors (ACEi) or mineralocorticoid receptor antagonists (MRAs) in patients with HFrEF has been associated with a decline in eGFR in post-hoc analyses [1,2]. In HFpEF patients, no renal benefits were observed with MRAs and an accelerated decline in renal function was observed with RAS inhibition [3-5]. In post-hoc analyses of HFrEF and HFpEF trials, decline in eGFR slowed with treatment of combined angiotensin-neprilysin inhibition [6,7].

This analysis examined the effect of sacubitril/valsartan on hard renal outcomes in heart failure and explored treatment effects according to ejection fraction by pre-specified pooling of data from the PARADIGM-HF and PARAGON-HF trials.


PARADIGM-HF and PARAGON-HF were randomized, double-blind trials in which sacubitril/valsartan was compared to a RAS inhibitor in patients with symptomatic heart failure and elevated natriuretic peptides. PARADIGM-HF enrolled 8399 patients with LVEF ≤40% and PARAGON-HF enrolled 4796 patients with LVEF ≥45%. One of the exclusion criteria was an eGFR<30 mL/min/1.73 m2 (at screening) or <25 mL/min/1.73 m2 (at randomization), or decrease >35% between screening and randomization.


The primary renal outcome was a composite of ≥50% reduction in eGFR, ESRD or death from renal causes.

Main results


In this pooled analysis of PARADIGM-HF and PARAGON-HF consisting of patients with HFrEF and HFpEF, treatment with sacubitril/valsartan resulted in a reduction of the composite renal outcome and slowed the decline in eGFR compared with RAS inhibition.

The reduction in the renal composite outcome with use of sacubitril/valsartan compared with RAS inhibition was independent of baseline renal function and most pronounced in those with baseline EF between 30% and 60%.


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Find this article online at Eur J Heart Fail

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