Τhe role of sacubitril/valsartan therapy on renal function and glucose metabolism in chronic heart failure patients

Heart failure (HF) is a complex clinical syndrome characterized by abnormalities in cardiac structure and function, dynamic remodelling, and perturbations of the neurohumoral axis. Recently, the angiotensin receptor neprilysin inhibitor (ARNi) class has been successfully tested in chronic systolic HF, improving morbidity and mortality. This treatment approach represents a potential shift in the treatment of HF from partial neurohumoral system inhibition to an integrated composite neurohumoral system modulation. As a substantial number of chronic HF patients show co-morbidities, especially diabetes mellitus and kidney dysfunction, this review is mainly focused on the role of ARNi on renal function and glucose metabolism. Emerging data support that sacubitril/valsartan might enhance glycaemic control in patients with diabetes and heart failure with reduced ejection fraction (HFrEF); while it improves kidney function. This was attributed to the combined effects of angiotensin blockade and augmentation of other neprilysin substrates by neprilysin inhibition and down titration of diuretic therapy. An understanding of emerging novel therapeutic class may provide important insights into the expected on-target and off-target effects when this agent is more widely prescribed.