Sacubitril/valsartan in Heart Failure and Beyond—From Molecular Mechanisms to Clinical Relevance

Abstract

As the ultimate pathophysiological event, heart failure (HF) may arise from various cardiovascular (CV) conditions, including sustained pressure/volume overload of the left ventricle, myocardial infarction or ischemia, and cardiomyopathies. Sacubitril/valsartan (S/V; formerly termed as LCZ696), a first-in-class angiotensin receptor/neprilysin inhibitor, brought a significant shift in the management of HF with reduced ejection fraction by modulating both renin-angiotensin-aldosterone system (angiotensin II type I receptor blockage by valsartan) and natriuretic peptide system (neprilysin inhibition by sacubitril) pathways. Besides, the efficacy of S/V has been also investigated in the setting of other CV pathologies which are during their pathophysiological course and progression deeply interrelated with HF. However, its mechanism of action is not entirely clarified, suggesting other off-target benefits contributing to its cardioprotection. In this review article our goal was to highlight up-to-date clinical and experimental evidence on S/V cardioprotective effects, as well as most discussed molecular mechanisms achieved by this dual-acting compound. Although S/V was extensively investigated in HF patients, additional large studies are needed to elucidate its effects in the setting of other CV conditions. Furthermore, with its antiinflamatory potential, this agent should be investigated in animal models of inflammatory heart diseases, such as myocarditis, while it may possibly improve cardiac dysfunction as well as inflammatory response in this pathophysiological setting. Also, discovering other signalling pathways affected by S/V should be of particular interest for basic researches, while it can provide additional understanding of its cardioprotective mechanisms.

Predicting Hospital Readmissions in Patients Receiving Novel-Dose Sacubitril/Valsartan Therapy: A Competing-Risk, Causal Mediation Analysis

“…A clear and early benefit of S/V was to reduce hospital readmissions of HF patients due to any causes. 7 McMurray et al and Desai et al pointed out all-cause readmission at 3 months or 1 year. 9 Unfortunately, there remained poor understanding of novel-dose S/V.…”

“…A clear and early benefit of S/V was to reduce hospital readmissions of HF patients due to any causes. 7 McMurray et al and Desai et al pointed out that S/V was superior to enalapril in improving HF patient outcomes. 3,8 Lately, Carnicelli et al reported that patients with higher adherence to S/V showed a significant reduction in all-cause readmission at 3 months or 1 year.…”

Predicting hospital readmissions in patients receiving novel-dose Sacubitril/Valsartan therapy: A competing-risk, causal mediation analysis

“…A clear and early benefit of S/V was to reduce hospital readmissions of HF patients due to any causes 11 . McMurray et al and Desai et al pointed out that S/V was superior to enalapril in improving HF patient outcomes 4,5 .…”

Vitamin D on Cardiac Function in Heart Failure: A Systematic Review and Meta-Analysis of 10 RCTs

“…Heart failure (HF) is a potential outcome of end stage of heart disease. It impairs the cardiac circulation due to a systolic and/or diastolic function damage of the heart [ 1 , 2 ]. HF occurs mainly due to remodeling of heart muscle cells [ 3 ].…”