Neprilysin Inhibition in Heart Failure with Reduced Ejection Fraction: A Clinical Review

  title={Neprilysin Inhibition in Heart Failure with Reduced Ejection Fraction: A Clinical Review},
  author={Jordan B. King and Adam P. Bress and Austin D. Reese and Mark A. Munger},
  journal={Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy},
  • J. KingA. Bress M. Munger
  • Published 1 September 2015
  • Medicine
  • Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy
There has been a 10‐year hiatus in the approval of a new pharmacotherapy for patients with chronic heart failure with a reduced ejection fraction (HFrEF). Combining an angiotensin receptor blocker, valsartan, with sacubitril, an inhibitor of neprilysin, results in increasing levels of natriuretic peptides that counterbalance high circulating levels of neurohormones in HFrEF. This has resulted in the development of a new agent, LCZ696. A comprehensive overview of LCZ696, its pharmacology, its… 

Cost-Effectiveness of SacubitrilValsartan in Patients With Heart Failure With Reduced Ejection Fraction

Treatment with sacubitrilvalsartan reduced cardiovascular mortality, decreased hospitalizations and emergency department (ED) visits for heart failure, and improved quality of life compared with enalapril therapy, according to an independent analysis of the cost-effectiveness.

ECG Monitoring of Reactions to Sacubitril-valsartan in Heart Failure with Reduced Ejection Fraction

  • M. Kang
  • Medicine
    Journal of cardiovascular imaging
  • 2020 Sacubitril/valsartan is an angiotensin receptor neprilysin inhibitor (ARNI) which is FDAapproved for the treatment of patients with chronic heart failure with reduced ejection

Increased natriuretic peptides not associated with heart failure

The mechanisms of increasing NPs and their diagnostic value in heart failure, as well as a number of other conditions, such as acute coronary syndrome and coronary artery disease, atrial fibrillation, exercise, kidney failure, taking cardiotoxic drugs (chemotherapy) and sacubitril/valsartan are discussed.

The Impact of Angiotensin Receptor–Neprilysin Inhibitors on Arrhythmias in Patients with Heart Failure: A Systematic Review and Meta-analysis

The use of ARNIs confers a reduction in composite outcomes of SCD and ventricular arrhythmias among patients with heart failure, mainly driven by SCD reduction in patients treated with ARnIs.

Sacubitril/Valsartan: A Game Changer in the Treatment for Heart Failure HFrEF, PARADIGM-HF, angiotensin receptor neprilysin inhibitor (ARNI)

The PARADIGM-HF trial provided compelling evidence for the cardiovascular and mortality benefit of sacubitril/valsartan when compared to enalapril in patients with heart failure and reduced ejection fraction, and the current role and future uses of this combination drug are discussed.

New Novel Treatment Approaches for Heart Failure With Reduced Ejection Fraction

A review of sacubitril–valsartan and ivabradine, currently approved for use in heart failure with reduced ejection fraction, present as novel approaches to further improve prognosis and outcomes in patients with HF.

Focus on the Novel Cardiovascular Drug LZC696: from Evidence to Clinical Consideration

Accumulating evidence suggests its potential use in heart failure with preserved ejection fraction (HFpEF), chronic kidney disease (CKD), post-myocardium infarction (post-MI) and stroke, and some special issues should be considered before its implementation in clinical practice.

Sacubitril/Valsartan: The Role of Neprilysin Pathway in Heart Failure

According to the results, NEP inhibition leads to a rise in the level of vasodilator agents and is beneficial for HF patients previously prescribed solely RAAS inhibiting agent, as well as reducing the morbidity and mortality rates of patients suffering from HF with reduced ejection fraction.

Natriuretic Peptides in Clinical Practice.

Natriuretic peptides have been reviewed for their updated information and new recommendations in heart failure and also potential role of these biomarkers in the management of various clinical conditions have been addressed in the form of expert opinion based on the available data in the literature.



First‐in‐Class Angiotensin Receptor Neprilysin Inhibitor in Heart Failure

LCZ696, an angiotensin receptor neprilysin inhibitor composed of a nepriolysisin inhibitor prodrug and the angiotENSin receptor antagonist valsartan, has proven effective in hypertension, has shown promise in a pilot trial of heart failure with preserved ejection fraction, and is being tested in a large outcomes trial ofheart failure with reduced ejections fraction.

Neprilysin inhibition to treat heart failure: a tale of science, serendipity, and second chances

  • J. McMurray
  • Biology
    European journal of heart failure
  • 2015
The role of neprilysin in the degradation of natriuretic and other vasoactive peptides, including bradykinin and adrenomedullin is described and the implications of the compelling benefits of LCZ696 compared with enalapril in the Prospective comparison of ARNI with ACEI to Determine impact on Global Mortality and morbidity in Heart Failure trial is discussed.

Angiotensin-neprilysin inhibition versus enalapril in heart failure.

LCZ696 was superior to enalapril in reducing the risks of death and of hospitalization for heart failure and decreased the symptoms and physical limitations of heart failure.

Angiotensin Receptor Neprilysin Inhibition Compared With Enalapril on the Risk of Clinical Progression in Surviving Patients With Heart Failure

Angiotensin-neprilysin inhibition prevents the clinical progression of surviving patients with heart failure more effectively than angiotens in-converting enzyme inhibition.

Combined neprilysin and renin-angiotensin system inhibition for the treatment of heart failure.

A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure.

Valsartan significantly reduces the combined end point of mortality and morbidity and improves clinical signs and symptoms in patients with heart failure, when added to prescribed therapy, and raises concern about the potential safety of this specific combination.

Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure.

The addition of enalapril to conventional therapy significantly reduced mortality and hospitalizations for heart failure in patients with chronic congestive heart failure and reduced ejection fractions.

Comparison of Omapatrilat and Enalapril in Patients With Chronic Heart Failure: The Omapatrilat Versus Enalapril Randomized Trial of Utility in Reducing Events (OVERTURE)

Omapatrilat reduces the risk of death and hospitalization in chronic heart failure but was not more effective than ACE inhibition alone in reducing therisk of a primary clinical event.