Combined RAAS and NEP Inhibition

Giuseppe Vergaro,Marco Metra

doi:10.17987/icfj.v17i0.601

Abstract

The neurohormonal model of HF has provided the rationale for the use of drug classes blocking the effectors of both the RAAS and SNS at different sites, including angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), mineralocorticoid receptor antagonists (MRA), and beta-blockers. Combined NEP and ACE blockade although unsuccessful with omapatrilat in the OVERTURE trial, found success with sacubitril/valsartan in the Paradigm-HF trial. The results of PARADIGM-HF trial represent one of the most significant breakthroughs in the management of HF of the last decade, representing a shift from neurohomonal antagonism to neurohormonal modulation.

Highlights

Neurohormonal activation in heart failure After the pivotal observations by Cohn et al concerning the significance of increased circulating concentrations of neurohormonal markers norepinephrine, plasma renin activity, and arginine vasopressin in patients with congestive heart failure (HF)[1], the neurohormonal model has become the main interpretative framework of the pathophysiology of HF in the last three decades.[2]
The neurohormonal model of HF has provided the rationale for the use of drug classes blocking the effectors of both the RAAS and SNS at different sites, including angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), mineralocorticoid receptor antagonists (MRA), and betablockers
Summary of major clinical trials testing the effects of angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin II type I receptor blockers (ARBs) in patients with heart failure and/or left ventricular dysfunction

Summary

Introduction

Neurohormonal activation in heart failure After the pivotal observations by Cohn et al concerning the significance of increased circulating concentrations of neurohormonal markers norepinephrine, plasma renin activity, and arginine vasopressin in patients with congestive heart failure (HF)[1], the neurohormonal model has become the main interpretative framework of the pathophysiology of HF in the last three decades.[2].

Results

Conclusion