Physicians' Academy for Cardiovascular Education

Worsening of renal function in heart failure patients slowed down by ARNI, particularly in type 2 diabetic patients

Literature -

Renal Effects and Associated Outcomes During Angiotensin-Neprilysin Inhibition in Heart Failure

Damman K, Gori M, Claggett B, et al. J Am Coll Cardiol HF 2018; published online ahead of print

Effect of neprilysin inhibition on renal function in patients with type 2 diabetes and chronic heart failure who are receiving target doses of inhibitors of the renin-angiotensin system: a secondary analysis of the PARADIGM-HF trial.

Packer M, Claggett B, Lefkowitz MP, et al. Lancet Diabetes Endocrinol 2018; published online ahead of print

Introduction and methods

Sacubitril/valsartan has been associated with a reduced risk of death and hospitalization compared with enalapril in patients with heart failure and reduced ejection fraction (HFrEF), and with an increase of the urinary albumin/creatinine ratio (UACR) in patients with heart failure and preserved ejection fraction (HFpEF) [1,2].

In one of these analyses of the PARADIGM-HF (Prospective Comparison of ARNI with ACE inhibition to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial [3], the effects of sacubitril/valsartan and enalapril on renal function and outcomes were evaluated. The other analysis assessed the effects of the same study medication on renal function in patients with and those without type 2 diabetes (T2DM).

In the PARADIGM-HF study, patients with New York Heart Association II-IV, an EF <40%, and elevated biomarkers, were randomized to receive either enalapril 10 mg or sacubitril/valsartan 97/103 mg twice daily, in a 1:1 ratio, after a run-in phase to test for tolerability. Patients with an estimated glomerular filtration rate (eGFR) of <30 ml/min/1.73 m2 were excluded from the study. Other major exclusion criteria were symptomatic hypotension and hyperkalemia..

eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation [4]. In a subset of patients, urinary albumin and creatinine concentrations, measured in spot urine samples were used to calculate the urinary albumin and creatinine ratio (UACR). The pre-specified renal endpoint was time to first occurrence of any of:

Main results


In HFrEF patients, compared with enalapril, sacubitril/valsartan led to a slower rate of decrease in the eGFR, even in patients with CKD, despite causing a modest increase in UACR. Moreover, compared to enalapril, sacubitril/valsartan decelerated the deterioration of renal function in type 2 diabetic patients with HFrEF.


Show references

Find Damman et al. online at J Am Coll Cardiol HF Find Packer et al. online at J Am Coll Cardiol HF

Share this page with your colleagues and friends: