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.

Sacubitril/Valsartan in Heart Failure Hospitalization: Two Pills a Day to Keep Hospitalizations Away?

“…Recently, this therapeutic approach has been further enhanced. Because NPs are degraded by the enzyme neprilysin, the endothelial endopeptidase, it was proposed that its inhibition could be an important therapeutic target in HF [ 17 ]. In the past years, we had four pillars in HF pharmacological treatment, which include sacubitril/valsartan as a primary option for treating chronic HF by replacing renin-angiotensin system inhibitors [ 5 ].…”

“…However, neprilysin also causes the degradation of other substrates favoring remodeling, such as angiotensin II (ATII) [ 19 ]. It results in reflex activation of the RAAS system [ 17 ]. Thus, the neprilysin inhibitor sacubitril has been combined with an ATII antagonist, valsartan, to enhance its favorable effects.…”

“…Because drugs preventing cardiac remodeling are key to halting the progression of ventricular functional impairment and, in turn, improving the prognosis of patients with HFrEF, it is crucial to initiate the treatment early. The drugs that slow the progression of damaging cardiac remodeling are ACEI, ARB II, and MRA, whereas the drugs that induce reverse cardiac remodeling, causing an appreciable decrease in ventricular volumes and an increase in LVEF are beta-blockers, cardiac resynchronization therapy, and ARNI [ 17 ]. Overall, PARAGON-HF is the only study that evaluated sacubitril/valsartan in HFpEF.…”

The long non-coding RNA NEAT1 regulates the transcriptional landscape of cardiomyocytes

“…Currently, the available treatment options are mostly limited to β-blockers, angiotensin receptor-neprilysin inhibitors (ARNi), and calcium agonists. 1 Long non-coding RNAs are transcripts over >200nts length lacking the ability to code for any protein. Several lncRNAs have been identified to contribute to the development of cardiac hypertrophy.…”