Sacubitril/valsartan (Entresto; Novartis) was shown to help preserve kidney function in patients with heart failure with reduced ejection fraction (HFrEF), with a more pronounced effect seen in a subgroup of patients who had both HFrEF and diabetes, according to a study published in The Lancet Diabetes & Endocrinology

The randomized, double-blind PARADIGM-HF study (N=8,399) evaluated sacubitril/valsartan 97mg/103mg twice daily vs enalapril 10mg twice daily in patients with mild-to-moderate chronic heart failure and systolic dysfunction. The secondary analysis looked at the change in estimated glomerular filtration rate (eGFR) over a 44-month follow-up period in patients with and without diabetes. 

The results showed that in patients with HFrEF without diabetes, eGFR decreased by 1.1mL/min/1.73m2, while those with diabetes saw a reduction in eGFR of 2.0mL/min per 1.73m2. Compared with the enalapril-treated group, those treated with sacubitril/valsartan were found to have significantly slower kidney decline (-1.3 vs -1.8mL/min/1.73m2 per year; P<0.0001). 

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Specifically, among patients with diabetes, the magnitude of effect with sacubitril/valsartan was found to be larger than in those without diabetes (+0.6 vs +0.3mL/min/1.73m2 per year; P=0.038). However, the incremental benefit seen in patients with diabetes was no longer significant when eGFR changes were adjusted for urinary cyclic guanosine monophosphate (P=0.41). 

The authors concluded that “in patients in whom the renin-angiotensin system is already maximally blocked, the addition of neprilysin inhibition attenuates the effect of diabetes to accelerate the deterioration of renal function that occurs in patients with chronic heart failure.”

Entresto combines sacubitril, a neprilysin inhibitor, and valsartan, an angiotensin II receptor blocker (ARB). It is currently indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA Class II–IV) and reduced ejection fraction. It is usually administered in conjunction with other heart failure therapies, in place of an ACE inhibitor or other ARB.

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