Sacubitril-Valsartan And 5-Year Incidence Of Neurocognitive Diagnoses

Grewal, Prabhjot; Yoo, Jeanwoo; Myserlis, Evangelos Pavlos; Skopicki, Hal A.; Kalogeropoulos, Andreas P.

doi:10.1016/j.cardfail.2022.03.030

Cited by 3 publications

(4 citation statements)

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“…He suggested that other Aβ clearance pathways exist in the brain that compensates for any decreased clearance related to neprilysin inhibition. Grewal et al 48 detected that the incidence of neurocognitive diagnoses was lower among sacubitril/valsartan combination recipients in a large-cohort, propensity-matched analysis of systolic heart failure patients.…”

Section: Discussionmentioning

confidence: 99%

Study of the possible effect of sacubitril/valsartan combination versus valsartan on the cognitive function in Alzheimer’s disease model in rats

Hussein

Nour

Khorshid

et al. 2023

Int J Immunopathol Pharmacol

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Objectives: Alzheimer’s disease (AD) is an irreversible, progressive neurodegenerative disorder. The proportion of elderly individuals at risk for AD and cardiovascular problems increases by raising life expectancy. The present study was designed to investigate the effect of the sacubitril/valsartan combination compared to that of valsartan alone in a rat model of AD. Methods: 72 male adult Wistar rats were divided into seven groups; control untreated rats received saline, control valsartan-treated rats received valsartan orally, control sacubitril/valsartan treated rats received sacubitril/valsartan orally, model rats received aluminum chloride i.p., model valsartan treated rats received aluminum chloride i.p. and valsartan orally and model sacubitril/valsartan treated rats received aluminum chloride i.p. and sacubitril/valsartan combination orally. All previous treatments continued on a daily basis for 6 weeks. At the second, fourth, and sixth weeks of the experiment, behavioral changes were evaluated using the Morris water maze and novel object recognition tests, and systolic blood pressure was measured. In the end, rat brain malondialdehyde and amyloid-beta 1-42 levels were measured, and the isolated hippocampus was evaluated histopathologically. Results: Valsartan improved AD symptoms in the aluminum-induced rat model, while the sacubitril/valsartan combination significantly worsened all tested parameters in both control and model rats compared with untreated and valsartan-treated animals. Conclusion: Based on the current study’s findings, valsartan did not increase the risk for AD development in control rats and improved AD symptoms in a rat model, while sacubitril/valsartan combination increased the risk of AD in control rats and worsened the condition in a rat model.

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Section: Discussionmentioning

confidence: 99%

Study of the possible effect of sacubitril/valsartan combination versus valsartan on the cognitive function in Alzheimer’s disease model in rats

Hussein

Nour

Khorshid

et al. 2023

Int J Immunopathol Pharmacol

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“…LCZ696 had no difference in the incidence of adverse events or serious adverse events compared to ARBs 56 suggesting that LCZ696 has a greater antihypertensive efficacy and an equal tolerability profile. Despite theoretical concerns regarding the incidence of neurocognitive impairments with the use of LCZ696, a large cohort study showed that neurocognition in patients with heart failure on LCZ696 did not differ from that on ACEIs or ARBs 57 . The potential exists that treatment of LCZ696 through the inhibition of NEP by LBQ657 may result in accumulation of Aβ.…”

Section: Nep Inhibitors In Admentioning

confidence: 99%

“…Despite theoretical concerns regarding the incidence of neurocognitive impairments with the use of LCZ696, a large cohort study showed that neurocognition in patients with heart failure on LCZ696 did not differ from that on ACEIs or ARBs. 57 The potential exists that treatment of LCZ696 through the inhibition of NEP by trials with 11,821 subjects included in meta-analysis showed no any risk for the development of cognitive impairment in patients on LCZ696 treatment. 58 A recent clinical trial on 592 patients from 137 centres in 20 countries were randomized 1:1 to either LCZ696 (target dose 97/103 mg twice daily) or valsartan (target dose 160 mg twice daily) showed no evidence that NEP inhibition increased the risk of cognitive impairment in patients with heart failure.…”

Section: Clinical Findingsmentioning

confidence: 99%

“…Despite theoretical concerns regarding the incidence of neurocognitive impairments with the use of LCZ696, a large cohort study showed that neurocognition in patients with heart failure on LCZ696 did not differ from that on ACEIs or ARBs. 57 The potential exists that treatment of LCZ696 through the inhibition of NEP by LBQ657 may result in accumulation of Aβ. In a double‐blind, randomized, parallel‐group, placebo‐controlled study, healthy subjects received once daily LCZ696 (400 mg, n = 21) or placebo ( n = 22) for 14 days showed that LCZ696 did not cause changes in CSF levels of Aβ 1‐42 compared with placebo, despite achieving CSF concentrations of LBQ657 sufficient to inhibit NEP.…”

Section: Nep Inhibitors In Admentioning

confidence: 99%

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Neprilysin inhibitors and risk of Alzheimer's disease: A future perspective

Ali,

Al‐Kuraishy,

Al‐Gareeb

et al. 2023

J Cellular Molecular Medi

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Alzheimer's disease (AD) is a heterogeneous neurodegenerative disease with multifaceted neuropathological disorders. AD is characterized by intracellular accumulation of phosphorylated tau proteins and extracellular deposition of amyloid beta (Aβ). Various protease enzymes, including neprilysin (NEP), are concerned with the degradation and clearance of Aβ. Indeed, a defective neuronal clearance pathway due to the dysfunction of degradation enzymes might be a possible mechanism for the accumulation of Aβ and subsequent progression of AD neuropathology. NEP is one of the most imperative metalloproteinase enzymes involved in the clearance of Aβ. This review aimed to highlight the possible role of NEP inhibitors in AD. The combination of sacubitril and valsartan which is called angiotensin receptor blocker and NEP inhibitor (ARNI) may produce beneficial and deleterious effects on AD neuropathology. NEP inhibitors might increase the risk of AD by the inhibition of Aβ clearance, and increase brain bradykinin (BK) and natriuretic peptides (NPs), which augment the pathogenesis of AD. These verdicts come from animal model studies, though they may not be applied to humans. However, clinical studies revealed promising safety findings regarding the use of ARNI. Moreover, NEP inhibition increases various neuroprotective peptides involved in inflammation, glucose homeostasis and nerve conduction. Also, NEP inhibitors may inhibit dipeptidyl peptidase 4 (DPP4) expression, ameliorating insulin and glucagon‐like peptide 1 (GLP‐1) levels. These findings proposed that NEP inhibitors may have a protective effect against AD development by increasing GLP‐1, neuropeptide Y (NPY) and substance P, and deleterious effects by increasing brain BK. Preclinical and clinical studies are recommended in this regard.

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Autoregulation: mediators and renin–angiotensin system in diseases and treatments

Mansour

2023

Futur J Pharm Sci

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Background Hemodynamic regulation is a substantial part of the physiological integrity of the human body. It is based on the delivery of proper blood perfusion to every organ. Five primary vasoactive substances are nearly located throughout the human body, either released from the endothelium, prostanoids, nitric oxide (NO), and endothelin-1 (ET-1); or considered as hormones, bradykinin (BK) and natriuretic peptides (NPs). Main body The circulating mediators are in synchronization with the renin–angiotensin system (RAS) during the pathogenesis of the main vital organs, heart, kidney, lung, liver, and brain. The RAS system has been an extensive therapeutic approach for cardiovascular and renal diseases for decades, but more recently became a crucial regulator of hemodynamics in other organs after the actions of its components were detected in other organs. All the mentioned disorders here begin with the initiation of abnormal imbalance between vasoactive mediators which causes vascular dysfunction and histopathological situations that may induce oxidative stress which exaggerates the disorder if there is no clinical intervention. Conclusion We will review the currently identified signaling pathways and the possible relationships between those compounds elucidating how they interfere with serious diseases including cardiovascular diseases (CVDs), chronic kidney disease (CKD), pulmonary arterial hypertension (PAH), portal hypertension (PHT), and Alzheimer's disease (AD). Thus, this updated review summarizes years of work that aims to define the contribution of each mediator in both normal and pathological states, besides the drugs based on their activity and their places in either preclinical or clinical trials.

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Sacubitril-Valsartan And 5-Year Incidence Of Neurocognitive Diagnoses

Cited by 3 publications

References 0 publications

Study of the possible effect of sacubitril/valsartan combination versus valsartan on the cognitive function in Alzheimer’s disease model in rats

Study of the possible effect of sacubitril/valsartan combination versus valsartan on the cognitive function in Alzheimer’s disease model in rats

Neprilysin inhibitors and risk of Alzheimer's disease: A future perspective

Autoregulation: mediators and renin–angiotensin system in diseases and treatments

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