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

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REVIEW ARTICLE

Angiotensin II Receptor Blocker Neprilysin Inhibitor (ARNI): New Avenues in Cardiovascular Therapy M. Volpe1,2 • G. Tocci1,2 • A. Battistoni1 • S. Rubattu1,2

Received: 21 April 2015 / Accepted: 10 June 2015 Ó Springer International Publishing Switzerland 2015

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 & M. Volpe [email protected] 1

Division of Cardiology, Department of Clinical and Molecular Medicine, Sapienza University of Rome, Via di Grottarossa 1035-1039, 00189 Rome, Italy

2

IRCCS Neuromed, Pozzilli, IS, Italy

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

1 The Need for New The burden of cardiovascular disease (CVD) continues to increase worldwide. The final common pathway in CVD is heart failure (HF), which is often mediated by progressive uncontrolled hypertension. About a quarter of the worldwide adult population had hypertension in 2000, and this proporti