Dual Angiotensin Receptor and Neprilysin Inhibition with Sacubitril/Valsartan in Chronic Systolic Heart Failure

Lillyblad, Matthew P.

doi:10.1177/1060028015593093

Cited by 20 publications

(24 citation statements)

References 66 publications

(146 reference statements)

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“…It is a potent vasopeptidase inhibitor for both neprilysin and ACE [1]. Dose titration trials showed increase in natriuretic peptides and decrease in ACE activity.…”

Section: Neprilysin: the Latest Piece In The Neurohormonal Puzzlementioning

confidence: 98%

“…CNP is found mostly in the kidney, central nervous system, and vasculature and released in response to cytokines and endothelium-dependent agonists [3]. Natriuretic peptides can also be stimulated by angiotensin II and endothelium-1 [1].…”

Section: Focus On Neurohormonal Activationmentioning

confidence: 99%

“…With the availability of bedside hemodynamic monitoring, there was broad consensus that the triad of increased cardiac filling pressures, decreased cardiac output, and excessive peripheral vasoconstriction was central to the pathogenesis of heart failure. Therefore, therapy was directed towards optimization of preload and afterload using vasodilator drugs and improving myocardial contractility through inotropic stimulation [1]. Beginning in the late 1970s, the role of neurohormonal activation in the heart failure syndrome was recognized and this insight lead to the development of therapies that have greatly improved outcomes in heart failure patients.…”

Section: Introductionmentioning

confidence: 99%

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Neprilysin Inhibition as a PARADIGM Shift in Heart Failure Therapy

Hsiao

Greenberg

2016

Curr Heart Fail Rep

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Heart failure is a growing global public health problem. With the aging population, increased risk factors for heart failure development, and better survival after myocardial infarction, the prevalence is only expected to increase in the coming years. Although existing therapies have improved the clinical course of heart failure patients, new approaches are urgently needed to enhance quality of life and reduce morbidity and mortality. However, there has been little progress in the treatment of chronic heart failure in the past decade with only two new drugs approved by the US FDA over this time. Better understanding of the neurohormonal axis of heart failure has lead to the development of LCZ696, a first-in-class novel agent that acts as an angiotensin receptor blocker and neprilysin inhibitor. In the PARADIGM-HF study, LCZ696 was superior to an angiotensin-converting enzyme inhibitor in reducing mortality and HF hospitalizations and improving quality of life across a broad spectrum of symptomatic patients with heart failure with reduced ejection fraction. While evaluation of long-term effects is still needed, the completed trials on LCZ696 demonstrate that the drug is generally well-tolerated with a safe side effect profile. LCZ696 should be strongly considered as a favorable alternative to angiotensin converting enzyme inhibitors and angiotensin receptor blockers in appropriate heart failure patients.

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“…It is a potent vasopeptidase inhibitor for both neprilysin and ACE [1]. Dose titration trials showed increase in natriuretic peptides and decrease in ACE activity.…”

Section: Neprilysin: the Latest Piece In The Neurohormonal Puzzlementioning

confidence: 98%

Section: Focus On Neurohormonal Activationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Neprilysin Inhibition as a PARADIGM Shift in Heart Failure Therapy

Hsiao

Greenberg

2016

Curr Heart Fail Rep

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“…58,59 The most challenging part is to reciprocate these results in general population in clinical practice.…”

Section: Challenges Of Paradigm-hf Trial In Clinical Practicementioning

confidence: 99%

Combined Neprilysin and RAS Inhibition in Cardiovascular Diseases: A Review of Clinical Studies

Tummala

Bhadra

Gupta³

et al. 2016

Journal of Cardiovascular Pharmacology

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The aim of this comprehensive review article is to emphasize on the possible exploration of a new therapeutic approach in the management of heart failure (HF) and other cardiovascular diseases: the renin-angiotensin-aldosterone system-neprilysin combination inhibitors, also called angiotensin receptor neprilysin inhibitor, valsartan/sacubitril (LCZ696). Sacubitril is an inhibitor of neutral endopeptidase (NEP) which degrades vasoactive peptides such as atrial natriuretic peptide and brain natriuretic peptide. Valsartan is an angiotensin receptor blocker which is usually used in hypertension. Although HF has been a global health burden, for decades there has been lack of novel therapeutic options as many trials failed due to potential side effects. With the published results of the landmark trial Prospective comparison of ARNI with ACEI to Determine the Impact on Global Mortality and morbidity in HF (PARADIGM-HF), a new direction in the treatment of HF is anticipated. This trial showed that LCZ696 was able to reduce the primary composite end point of cardiovascular death or HF hospitalization, and similar reduction was observed for cardiovascular death. This review article also highlights the results of 4 published trials of LCZ696 in both HTN and HF. After the results of PARADIGM-HF trial, the major challenge will be outcome in regular clinical practice, as subjects in the trial were mostly stable New York Heart Association class II patients with no comorbidities. In addition, many trials are simultaneously in progress regarding the use of LCZ696 in patients with diabetes, renal failure, and hepatic impairment. To conclude, sacubitril/valsartan significantly improved morbidity and mortality in patients with chronic HF, but it will need meticulous attention when used in real outpatient practice.

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“…Valsartan acts on the angiotensin-aldosterone system, thereby reducing vasoconstriction, sodium and water retention and ventricular remodelling 2,8,10. The active metabolite of sacubitril inhibits the enzyme neprilysin, an endopeptidase that degrades vasoactive natriuretic peptides, bradykinin and angiotensin II, leading to an increased concentration of the endogenous natriuretic peptides with enhancement of diuresis, natriuresis and vasodilation.…”

Section: What Is Sacubitril Valsartan?mentioning

confidence: 99%

▼ Sacubitril valsartan for heart failure

2016

DTB

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▼ Sacubitril valsartan (Entresto-Novartis) is a new oral drug licensed for the treatment of symptomatic chronic heart failure in adults with reduced ejection fraction.(1) It is described as an angiotensin receptor neprilysin inhibitor and contains the neprilysin inhibitor, sacubitril and the angiotensin II receptor antagonist, valsartan.(1-3) Here, we review the evidence for sacubitril valsartan and consider its place in the management of heart failure.

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Dual Angiotensin Receptor and Neprilysin Inhibition with Sacubitril/Valsartan in Chronic Systolic Heart Failure

Abstract: Sacubitril/valsartan significantly improved morbidity and mortality in patients with chronic HFrEF but will require careful application to "real-world" populations of HFrEF.

Cited by 20 publications

References 66 publications

Neprilysin Inhibition as a PARADIGM Shift in Heart Failure Therapy

Neprilysin Inhibition as a PARADIGM Shift in Heart Failure Therapy

Combined Neprilysin and RAS Inhibition in Cardiovascular Diseases: A Review of Clinical Studies

▼ Sacubitril valsartan for heart failure

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