The history and mystery of sacubitril/valsartan: From clinical trial to the real world

Zhang, Mingsong; Zou, Yifei; Wang, He; Sun, Wei; Liu, Bin

doi:10.3389/fcvm.2023.1102521

Cited by 7 publications

(2 citation statements)

References 126 publications

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“…Sacubitril is a prodrug that is activated to become a neprilysin inhibitor that reduces blood volume [ 82 ]. The combination of valsartan and sacubitril constitutes an important treatment for patients with heart failure [ 83 ]. These drugs do not have known interactions with enzalutamide [ 9 ].…”

Section: Enzalutamide With Specific Medication Classesmentioning

confidence: 99%

Enzalutamide: Understanding and Managing Drug Interactions to Improve Patient Safety and Drug Efficacy

Lennep,

Mack,

Poondru

et al. 2024

Drug Saf

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Enzalutamide is an oral androgen receptor signaling inhibitor utilized in the treatment of men with prostate cancer. It is a moderate inducer of the cytochrome P450 (CYP) enzymes CYP2C9 and CYP2C19, and a strong inducer of CYP3A4. It was also shown to be a mild inhibitor of the efflux transporter P-glycoprotein in patients with prostate cancer. Enzalutamide is primarily metabolized by CYP3A4 and CYP2C8. The risk of enzalutamide drug interactions arises primarily when it is coadministered with other drugs that interact with these CYPs, including CYP3A4. In this review, we begin by providing an overview of enzalutamide including its dosing, use in special populations, pharmacokinetics, changes to its prescribing information, and potential for interaction with coadministered drugs. Enzalutamide interactions with drugs from a wide range of medication classes commonly prescribed to patients with prostate cancer are described, including oral androgen deprivation therapy, agents used to treat a range of cardiovascular diseases, antidiabetic drugs, antidepressants, anti-seizure medications, common urology medications, analgesics, proton pump inhibitors, immunosuppressants, and antigout drugs. Enzalutamide interactions with common vitamins and supplements are also briefly discussed. This review provides a resource for healthcare practitioners and patients that will help provide a basis for the understanding and management of enzalutamide drug–drug interactions to inform decision making, improve patient safety, and optimize drug efficacy.

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Section: Enzalutamide With Specific Medication Classesmentioning

confidence: 99%

Enzalutamide: Understanding and Managing Drug Interactions to Improve Patient Safety and Drug Efficacy

Lennep,

Mack,

Poondru

et al. 2024

Drug Saf

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“…In recent years, more and more publications have appeared testifying to the high effectiveness of the angiotensin-receptor neprilysin inhibitor sacubitril/valsartan (S/V) in the complex of optimal HF drug therapy [7,11]. Among RAAS blockers, the potential advantages of S/V versus angiotensin-converting enzyme inhibitors (iACE) include the impact on the pathogenetic mechanisms of HF formation, in particular the recently established anti-inflammatory and antifibrotic effects, which are of significant relevance in the treatment of AM [13,18,20,21]. Therefore, timely optimisation of therapy to prevent HF progression in patients with AM is one of the primary tasks in clinical practice and has prognostic significance.…”

mentioning

confidence: 99%

Вибір Блокатора Ренін-Ангіотензин-Альдостеронової Системи Для Лікування Серцевої Недостатності При Гострому Міокардиті

Nesukay,

Kovalenko,

Cherniuk

et al. 2024

UJC

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The aim – to evaluate the effectiveness of sacubitril/valsartan and enalapril in heart failure treatment in patients with acute severe myocarditis with reduced left ventricular ejection fraction based on dynamic analysis of the heart structural and functional changes.Materials and methods. The study is based on the results of examinations of 90 patients with a severe course of acute myocarditis (AM) with reduced ejection fraction (EF) of the left ventricle (LV) – ≤40 %. The patients were divided into two groups: the 1st group included 48 patients who were treated with an angiotensin-converting enzyme (ACE) inhibitor – enalapril as part of heart failure (HF) therapy; the 2nd group included 42 patients with AM who received the sacubitril/valsartan combination instead of enalapril in the complex therapy of HF. All patients underwent a 6-minute walk test, echocardiography (EchoCG) with the speckle-tracking method, and cardiac magnetic resonance imaging (CMR). Examinations were carried out three times: in the 1st month from the onset of AM symptoms before the appointment of drug therapy, after 6 and 12 months of observation. Part of the patients from the 1st group, namely 25 patients (52.1 %) in whom the use of ACE inhibitors proved to be ineffective after six months, was transferred to the combination of sacubitril/valsartan (group 1A).Results and discussion. After six months of treatment, compared to the 1st group, the patients of the 2nd group were distinguished by better indicators of the structural and functional state of the heart, which characterise the contractility and volume of the LV – the values of LV EF and LV longitudinal global systolic strain (LGSS) were higher by 13,7 and 26.2 % respectively, LV end-diastolic volume index (EDVi) was 13.2% lower, as well as a 21.7 % lower number of LV segments in which delayed contrast was detected on cardiac MRI. After six months of taking the sacubitril/valsartan combination in 1A group patients, an improvement in the structural and functional state of the heart was also achieved: the values of LVEF and LGSS increased by 19.2 % and 27.9 %, respectively, and LV EDVi decreased by 19.0 %; the number of LV segments in which delayed enhancement was determined on cardiac MRI decreased by 30.7 %. With the help of regression analysis, it was established the presence of a set of factors that determine the priority of prescribing the sacubitril/valsartan combination as initial therapy in patients with severe myocarditis: presence of reduced LVEF – ≤40 %; pronounced decrease in longitudinal and circular global LV strain – ≤8.5 and ≤9.0 %, respectively; pronounced dilatation of the LV – EDVi ≥102 ml/m2; presence of III or higher HF functional class; presence of delayed enhancement in ≥ 5,0 LV segments according to cardiac MRI data.Conclusions. In patients with a severe course of myocarditis, the sacubitril/valsartan combination prescribed as initial therapy showed higher effectiveness compared to ACE inhibitors in terms of improving contractility and reducing LV dilatation, as well as improving the functional class of heart failure. A complex of factors has been established that prove the expediency of prescribing the sacubitril/valsartan combination as initial therapy for heart failure in patients with acute myocarditis.

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Effects of Sacubitril/Valsartan on Survival in Patients with Heart Failure and Significant Valvular Heart Disease

Lin,

Chao,

Chuang

et al. 2024

Clin Pharma and Therapeutics

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Although the benefits of sacubitril/valsartan in heart failure with reduced ejection fraction (HFrEF) are well established, patients with hemodynamically significant mitral regurgitation (MR) were excluded from pivotal trials. We aimed to assess the effects of sacubitril/valsartan on survival in patients with HFrEF and concomitant significant MR. All patients from a single center who underwent echocardiography between June 2008 and December 2020, with a left ventricular ejection fraction (LVEF) of less than 40% and hemodynamically significant MR were recruited. Patients were categorized according to drug use and year of the index echocardiogram into the angiotensin receptor/neprilysin inhibitor (ARNI), non‐ARNI before 2017, and non‐ARNI after 2017 groups. Patients in the ARNI and non‐ARNI after 2017 groups were compared directly, whereas patients in the non‐ARNI before 2017 group were matched to the ARNI group in a 3:1 ratio. The outcome of interest was all‐cause mortality. Death was compared between the groups using univariate and multivariate Cox proportional hazard models. After exclusion by criteria and matching, there remained 610 patients in the ARNI group, 434 in the non‐ARNI after 2017 group, and 1,722 in the non‐ARNI before 2017 group. During follow‐up, all‐cause mortality was significantly lower in the ARNI group compared with both non‐ARNI after 2017 and non‐ARNI before 2017 groups. Multivariate analysis of both pairs of comparison between groups found the use of ARNI to be significantly associated with increased survival. In patients with HFrEF and concomitant significant MR, treatment with sacubitril/valsartan was associated with lower risks of all‐cause death.

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The history and mystery of sacubitril/valsartan: From clinical trial to the real world

Cited by 7 publications

References 126 publications

Enzalutamide: Understanding and Managing Drug Interactions to Improve Patient Safety and Drug Efficacy

Enzalutamide: Understanding and Managing Drug Interactions to Improve Patient Safety and Drug Efficacy

Вибір Блокатора Ренін-Ангіотензин-Альдостеронової Системи Для Лікування Серцевої Недостатності При Гострому Міокардиті

Effects of Sacubitril/Valsartan on Survival in Patients with Heart Failure and Significant Valvular Heart Disease

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