entresto

Diarrhoea is an adverse drug reaction of the angiotensin receptor neprilysin inhibitor (ARNI) sacubitril + valsartan. It was also described with olmesartan and more recently with other angiotensin receptor blockers. The study was performed to compare diarrhoea reports in pharmacovigilance databases with sacubitril + valsartan and valsartan. The study used reports of diarrhoea with the ARNI sacubitril + valsartan registered: first in the French PharmacoVigilance Database (FPVD) and second in Vigibase®, the WHO Global Individual Case Safety Report database...

Chronic sympathetic nervous system (SNS) overactivity, characteristic of heart failure (HF) with reduced ejection fraction (HFrEF), is associated with poor prognosis and contributes to increased mortality risk. Sacubitril-valsartan is a recently approved, first-in-class, angiotensin receptor neprilysin inhibitor (ARNI) drug that markedly reduces the risks of death from cardiovascular causes and hospitalization for HF in patients with HFrEF, but the physiological mechanisms underlying these benefits are not fully understood...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

AIMS: Optimizing medical cardiac treatment for sleep apnoea (SA) in patients with chronic heart failure and reduced ejection fraction (HFrEF) is an expert Grade C recommendation based on six studies encompassing a total of 67 patients only. Whether sacubitril-valsartan (SV), a cornerstone of HFrEF medical treatment, impacts SA is unknown and requires evaluation. METHODS AND RESULTS: The ENTRESTO-SAS trial is a six-centre, prospective, open-label real-life cohort study (NCT02916160)...

Federal regulatory agencies such as the United States Food and Drug Administration review pharmacological evidence to ensure the safety and efficacy of new and repurposed pharmaceuticals prior to market approval. The discussions, disagreements and procedural decisions contained within such reviews offer unique insight into a pharmaceutical's strengths, weaknesses and opportunities, yet are often overlooked as a significant source of pharmacological information for research and development. To highlight the value of such resources, we present a case study on Entresto, a first-in-class angiotensin receptor-neprilysin inhibitor for the treatment of heart failure with reduced ejection fraction, and explore the regulatory rationale underlying its market approval...

No abstract text is available yet for this article.

With variable potencies atrial-, brain-type and c-type natriuretic peptides (NP)s, best documented for ANP and its analogues, promote sodium and water excretion, renal blood flow, lipolysis, lower blood pressure, and suppress renin and aldosterone secretion through interaction predominantly with cGMP-coupled NPR-A receptor. Infusion of especially ANP and its analogues up to 50 ng/kg/min in patients with high risk of acute kidney injury (cardiac vascular bypass surgery, intraabdominal surgery, direct kidney surgery) protects kidney function (GFR, plasma flow, medullary flow, albuminuria, renal replacement therapy, tissue injury) at short term and also long term and likely additively with the diuretic furosemide...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

A sensitive and accurate spectrofluorimetric method was proposed for the determination of Sacubitril calcium and Valsartan simultaneously in binary mixture. The method was established on measuring the native fluorescence of Sacubitril calcium and Valsartan upon excitation at 240 nm in acetonitrile. The emission of Sacubitril calcium was measured at 615 nm. For the determination Valsartan a first derivative ratio method was employed to eliminate any spectral interference. The ratio emission spectra were achieved by dividing the emission spectra of various concentrations of Valsartan by the emission spectrum of Sacubitril calcium (100 ng/ml) then the first derivative of the obtained ratio emission spectra was recorded using the proper smoothing factor...

Cardiac fibrosis is a significant component of pathological heart remodeling, yet it is not directly targeted by existing drugs. Systems pharmacology approaches have the potential to provide mechanistic frameworks with which to predict and understand how drugs modulate biological systems. Here, we combine network modeling of the fibroblast signaling network with 36 unique drug-target interactions from DrugBank to predict drugs that modulate fibroblast phenotype and fibrosis. Galunisertib was predicted to decrease collagen and α-smooth muscle actin expression, which we validated in human cardiac fibroblasts...

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Sacubitril/valsartan (Entresto™; LCZ696) is the first angiotensin receptor-neprilysin inhibitor (ARNI) drug approved by the US and EU for heart failure (HF) and especially recommended for hypertensive HF (HHF). Sacubitril inhibits the enzyme neprilysin (NEP) which produces both beneficial and adverse effects in the human body. While LCZ696 causes beneficial cardiovascular effects, it may induce memory and cognitive dysfunction, or even exacerbate Alzheimer's disease (AD). This article reviewed data reported by experimental and clinical studies that examined NEP inhibitors and their dementia-related side effects...

The role of sacubitril and/or valsartan in patient with heart failure (HF) is established. Whether sacubitril and/or valsartan plays a role in improving outcomes in patients after ST-segment elevation myocardial infarction (STEMI) is unknown. The current study aims to comparing the efficacy and safety of sacubitril and/or valsartan versus ramipril in post-STEMI patients. Patients presenting with STEMI were randomized to receive either sacubitril and/or valsartan or ramipril after primary percutaneous coronary intervention...

Sacubitril/Valsartan (S/V) is a novel and remarkably effective opportunity to treat heart failure with reduced ejection fraction (HFrEF). However, patients with HFrEF induced by cancer therapy were a priori excluded from the registration study. The value of S/V in this important subgroup of patients needs to be firmly established. In this issue of Cardio-Oncology, Gregorietti et al. report on the effects of S/V in a small group of cancer patients, primarily women with breast cancer treated with anthracyclines...

Objectives : This study investigated the impact of polymer excipients on a typical cocrystal for sacubitril (SAC) and valsartan (VAL), aiming to guide optional formulation design and maximize oral bioavailability. Methods : Poly vinyl pyrrolidone (PVP) and hydroxypropyl cellulose (HPC) and hydroxypropyl methylcellulose (HPMC) were selected. The dissolution/permeation system was used to predict both the kinetics of drug supersaturation and the simple permeation. The intermolecular interaction was analyzed by 1 H NMR spectroscopy and molecular dynamics simulation...

BACKGROUND: Peptide radioligands may serve as radionuclide carriers to tumor sites overexpressing their cognate receptor for diagnostic or therapeutic purposes. Treatment of mice with the neprilysin (NEP)-inhibitor phosphoramidon was previously shown to improve the metabolic stability and tumor uptake of biodegradable radiopeptides. Aiming to clinical translation of this methodology, we herein investigated the impact of the approved pill Entresto, releasing the potent NEP-inhibitor LBQ657 in vivo, on the stability and tumor uptake of two radiopeptides...

The Prospective comparison of ARNI with angiotensin-converting enzyme inhibitor to Determine Impact on Global Mortality and morbidity in Heart Failure trial identified a marked reduction in the risk of death and hospitalization for heart failure in patients with heart failure with reduced ejection fraction (HFrEF) treated with sacubitril-valsartan (trade name Entresto), but the physiological processes underpinning these improvements are unclear. We tested the hypothesis that treatment with sacubitril-valsartan improves peripheral vascular function, functional capacity, and inflammation in patients with HFrEF...

BACKGROUND: The overexpression of neurotensin subtype 1 receptors (NTS1Rs) in human tumors may be elegantly exploited for directing neurotensin (NT)-based radionuclide carriers specifically to cancer sites for theranostic purposes. We have recently shown that [99m Tc]Tc-DT1 ([99m Tc]Tc-[N4 -Gly7 ]NT(7-13)) and [99m Tc]Tc-DT5 ([99m Tc]Tc-[N4 - β Ala7 ,Dab9 ]NT(7-13)) show notably improved uptake in human colon adenocarcinoma WiDr xenografts in mice treated with neprilysin (NEP) inhibitors and/or angiotensin-converting enzyme (ACE) inhibitors compared with untreated controls...