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Use of angiotensin II receptor blocker and neprilysin inhibitor in heart failure with reduced ejection fraction

Author
Wilson S Colucci, MD
Section Editors
Stephen S Gottlieb, MD
Mariell Jessup, MD
Deputy Editor
Susan B Yeon, MD, JD, FACC

INTRODUCTION

Blockade of the renin-angiotensin-aldosterone system (RAAS) is a key component of treatment of patients with heart failure (HF) with reduced ejection fraction (HFrEF, also known as systolic HF or HF due to systolic dysfunction) [1]. RAAS blockade with angiotensin converting (ACE) inhibitor improves morbidity and mortality in these patients (figure 1). In clinical trials, angiotensin II receptor blocker (ARB) therapy reduced hospitalizations for HF and produced a borderline statistically significant reduction in mortality compared to placebo and is thus an alternative to ACE inhibitor therapy for patients with ACE inhibitor intolerance. (See "Overview of the therapy of heart failure with reduced ejection fraction".)

Augmentation of beneficial counter-regulatory systems such as natriuretic peptides is an additional strategy to treat HF [2]. Inhibition of neprilysin raises levels of several endogenous vasoactive peptides, including natriuretic peptides, bradykinin, and adrenomedullin. The combination of neprilysin inhibitor plus ARB therapy is used as an alternative to ACE inhibitor (or single agent ARB) therapy.

This topic will discuss the clinical evidence on and use of ARB and neprilysin inhibitor therapy in HFrEF. The role of ACE inhibitors in HFrEF and an overview of treatment of HFrEF are discussed separately. (See "Angiotensin converting enzyme inhibitors and receptor blockers in heart failure: Mechanisms of action" and "ACE inhibitors in heart failure with reduced ejection fraction: Therapeutic use" and "Overview of the therapy of heart failure with reduced ejection fraction".)

ANGIOTENSIN II RECEPTOR BLOCKER

Mechanism of action — Angiotensin II receptor blockers (ARBs) and angiotensin converting enzyme (ACE) inhibitors reduce the stimulation of angiotensin II (AT) receptors via different mechanisms (figure 2). Given the difference in mechanisms, it was previously postulated that ARB therapy would provide an advantage over ACE inhibitor therapy but the evidence has shown that ARB therapy is not superior to ACE inhibitor therapy for heart failure (HF).

ACE inhibitors block the formation of angiotensin II, thereby decreasing the amount of angiotensin available to both AT type 1 (AT1) and AT type 2 (AT2) receptors. ARBs selectively block the binding of angiotensin II to the AT1 receptor, but do not affect the AT2 receptor [3]. The clinical importance of this is uncertain, since the AT1 receptor seems to dominate. (See "Actions of angiotensin II on the heart" and "Differences between angiotensin-converting enzyme inhibitors and receptor blockers".)

                      

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Literature review current through: Nov 2016. | This topic last updated: Tue Oct 25 00:00:00 GMT+00:00 2016.
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