Combined RAAS and NEP Inhibition

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.