Angiotensin II Receptor Blocker Neprilysin Inhibitor (ARNI): New Avenues in Cardiovascular Therapy

M. Volpe, G. Tocci, A. Battistoni, S. Rubattu

Research output: Contribution to journalArticle

Abstract

The burden of cardiovascular disease (CVD) is continuously and progressively raising worldwide. Essential hypertension is a major driver of cardiovascular events, including coronary artery disease, myocardial infarction, ischemic stroke and congestive heart failure. This latter may represent the final common pathway of different cardiovascular diseases, and it is often mediated by progressive uncontrolled hypertension. Despite solid advantages derived from effective and sustained blood pressure control, and the widespread availability of effective antihypertensive medications, the vast majority of the more than 1 billion hypertensive patients worldwide continue to have uncontrolled hypertension. Among various factors that may be involved, the abnormal activation of neurohormonal systems is one consistent feature throughout the continuum of cardiovascular diseases. These systems may initiate biologically meaningful “injury responses”. However, their sustained chronic overactivity often may induce and maintain the progression from hypertension towards congestive heart failure. The renin–angiotensin–aldosteron system, the sympathetic nervous system and the endothelin system are major neurohormonal stressor systems that are not only able to elevate blood pressure levels by retaining water and sodium, but also to play a role in the pathophysiology of cardiovascular diseases. More recently, the angiotensin receptor neprilysin inhibitor (ARNI) represents a favourable approach to inhibit neutral endopeptidase (NEP) and suppress the RAAS via blockade of the AT1 receptors, without the increased risk of angioedema. LCZ696, the first-in-class ARNI, has already demonstrated BP lowering efficacy in patients with hypertension, in particular with respect to systolic blood pressure levels, improved cardiac biomarkers, cardiac remodelling and prognosis in patients with heart failure. This manuscript will briefly overview the main pathophysiological and therapeutic aspects of ARNI in the clinical management of hypertension and heart failure.

Original languageEnglish
Pages (from-to)241-246
Number of pages6
JournalHigh Blood Pressure and Cardiovascular Prevention
Volume22
Issue number3
DOIs
Publication statusPublished - Sep 10 2015

Fingerprint

Neprilysin
Angiotensin Receptor Antagonists
Hypertension
Cardiovascular Diseases
Heart Failure
Blood Pressure
Therapeutics
Angioedema
Angiotensin Receptors
Endothelins
Sympathetic Nervous System
Antihypertensive Agents
Coronary Artery Disease
Biomarkers
Sodium
Stroke
Myocardial Infarction
Water
Wounds and Injuries

Keywords

  • Angiontesin II
  • Angiotensin receptor neprilysin inhibitor
  • Heart failure
  • Hypertension
  • Neutral endopeptidase
  • receptor blockers
  • Renin–angiotensin–aldosterone system

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Internal Medicine

Cite this

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title = "Angiotensin II Receptor Blocker Neprilysin Inhibitor (ARNI): New Avenues in Cardiovascular Therapy",
abstract = "The burden of cardiovascular disease (CVD) is continuously and progressively raising worldwide. Essential hypertension is a major driver of cardiovascular events, including coronary artery disease, myocardial infarction, ischemic stroke and congestive heart failure. This latter may represent the final common pathway of different cardiovascular diseases, and it is often mediated by progressive uncontrolled hypertension. Despite solid advantages derived from effective and sustained blood pressure control, and the widespread availability of effective antihypertensive medications, the vast majority of the more than 1 billion hypertensive patients worldwide continue to have uncontrolled hypertension. Among various factors that may be involved, the abnormal activation of neurohormonal systems is one consistent feature throughout the continuum of cardiovascular diseases. These systems may initiate biologically meaningful “injury responses”. However, their sustained chronic overactivity often may induce and maintain the progression from hypertension towards congestive heart failure. The renin–angiotensin–aldosteron system, the sympathetic nervous system and the endothelin system are major neurohormonal stressor systems that are not only able to elevate blood pressure levels by retaining water and sodium, but also to play a role in the pathophysiology of cardiovascular diseases. More recently, the angiotensin receptor neprilysin inhibitor (ARNI) represents a favourable approach to inhibit neutral endopeptidase (NEP) and suppress the RAAS via blockade of the AT1 receptors, without the increased risk of angioedema. LCZ696, the first-in-class ARNI, has already demonstrated BP lowering efficacy in patients with hypertension, in particular with respect to systolic blood pressure levels, improved cardiac biomarkers, cardiac remodelling and prognosis in patients with heart failure. This manuscript will briefly overview the main pathophysiological and therapeutic aspects of ARNI in the clinical management of hypertension and heart failure.",
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AU - Rubattu, S.

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