Angiotensin receptor blocker neprilysin inhibitors

Abstract

Heart failure (HF) is a clinical syndrome that results from a structural or functional cardiac disorder that reduces the ability of the ventricle of the heart to fill with, or eject, blood. It is a multifaceted clinical condition that affects up to 2% of the population in the developed world, and is linked to significant morbidity and mortality; it is therefore considered a major concern for public health. Regarding the mechanism of HF, three neurohumoral factors - the renin-angiotensin-aldosterone system, the sympathetic nervous system, and natriuretic peptides — are related to the pathology of chronic HF (CHF), and the targets of treatment. Angiotensin receptor blocker and neprilysin inhibitor (angiotensin-receptor neprilysin inhibitor), namely sacubitril/valsartan (SAC/VAL), has been introduced as a treatment for CHF. SAC/VAL is an efficacious, safe, and cost-effective therapy that improves quality of life and longevity in patients with HF with reduced ejection fraction (HFrEF), and reduces hospital admissions. An in-hospital initiation strategy offers a potential new avenue to improve the clinical uptake of SAC/VAL. In the last five years, SAC/VAL has been established as a cornerstone component of comprehensive disease-modifying medical therapy in the management of chronic HFrEF. On the other hand, further work, with carefully designed and controlled preclinical studies, is necessary for understanding the molecular mechanisms, effects, and confirmation of issues such as long-term safety in both human and animal models.

Keywords: Angiotensin receptor blocker and neprilysin inhibitor; Chronic heart failure; Renin-angiotensin-aldosterone-system; Sympathetic nervous system; Natriuretic peptide; Sacubitril/valsartan

Core Tip: Heart failure (HF) is a multi-faceted clinical condition that affects up to 2% of the population in the developed world, and is linked to significant morbidity and mortality; it is therefore considered a major concern for public health. In 2014, a newly developed angiotensin receptor blocker and neprilysin inhibitor (angiotensin-receptor neprilysin inhibitor), namely sacubitril/valsartan (SAC/VAL), was introduced as a treatment for chronic HF (CHF), and it proved to have the efficacy, safety, and cost-effectiveness to improve quality of life and longevity in patients with heart failure with reduced ejection fraction and reduces hospital admission. In this review, we first summarize the current knowledge regarding HF, then provide an overview of the current knowledge on SAC/VAL for CHF, together with relevant clinical trials and future perspectives.