Neutral Endopeptidase Inhibitors and Endothelin Antagonists

The current treatment paradigm for heart failure revolves around the central theory of neurohormonal antagonism. With the success of angiotensin-converting–enzyme inhibition, beta-blockade, and aldosterone antagonism in heart failure, alternative areas of the hormonal cascade have been targeted for potential benefits. Two such agents, neutral endopeptidase inhibitors and endothelin antagonists, have demonstrated promising initial results in animal models and small, human-based studies but have fallen short when examined in larger clinical trials. The reasons for these shortcomings are varied and require analysis of the design of the studies as well as the intrinsic functions of these agents.