Renal protection in chronic heart failure: focus on sacubitril/valsartan

Eur Heart J Cardiovasc Pharmacother. 2021 Sep 21;7(5):445-452. doi: 10.1093/ehjcvp/pvab030.


Chronic kidney disease (CKD) is highly prevalent in patients with chronic heart failure (CHF) and increases the risk of overall and cardiovascular (CV) mortality. Despite evidence supporting the effectiveness of angiotensin-converting enzyme inhibitors (ACE-Is), angiotensin receptor blockers, and mineralocorticoid receptor antagonists in decreasing mortality in patients with CHF, CKD hampers the optimization of standard pharmacologic therapy for heart failure. Therefore, other treatment options are needed to optimize treatment outcomes in CHF patients with CKD. The first-in-class angiotensin receptor-neprilysin inhibitor, sacubitril/valsartan, has a complementary activity that counteracts the potential unwanted long-term effects of over-activation of the renin-angiotensin-aldosterone system. Sacubitril/valsartan reduced the risk of CV mortality compared to standard therapy with an ACE-I in patients with heart failure with reduced ejection fraction (HFrEF) in the PARADIGM-HF trial and has been shown to be safe and effective in a broad range of HFrEF patients. However, data on the efficacy and tolerability of sacubitril/valsartan in patients with more advanced CKD are limited. This review discusses the evidence for the role of sacubitril/valsartan in providing additional renal benefit in patients with HFrEF. Data from clinical trials and real-world experience in patients with HFrEF and advanced CKD support the benefits of dual angiotensin/neprilysin inhibition across the breadth of kidney disease stages, including patients with significant renal impairment that was not reported in the pivotal PARADIGM-HF trial, and suggests a central role for the cardiac benefits of sacubitril/valsartan in nephroprotection.

Keywords: Chronic heart failure; Chronic kidney disease; Renal function; Renoprotection; Sacubitril/valsartan.

Publication types

  • Review

MeSH terms

  • Aminobutyrates
  • Biphenyl Compounds
  • Heart Failure* / diagnosis
  • Heart Failure* / drug therapy
  • Humans
  • Stroke Volume
  • Tetrazoles / adverse effects
  • Valsartan / therapeutic use


  • Aminobutyrates
  • Biphenyl Compounds
  • Tetrazoles
  • sacubitril
  • Valsartan