Angiotensin receptor neprilysin inhibition in heart failure: mechanistic action and clinical impact.
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Heart failure (HF) is an increasingly common syndrome associated with high mortality and economic burden, and there has been a paucity over the past decade of new pharmacotherapies that improve outcomes. However, recent data from a large randomized controlled trial compared the novel agent LCZ696, a dual-acting angiotensin receptor blocker and neprilysin inhibitor (ARNi), with the well established angiotensin-converting enzyme (ACE) inhibitor enalapril and found significant reduction in mortality among the chronic reduced ejection fraction HF population. Preclinical and clinical data suggest that neprilysin inhibition provides beneficial outcomes in HF patients by preventing the degradation of natriuretic peptides and thereby promoting natriuresis and vasodilatation and counteracting the negative cardiorenal effects of the up-regulated renin-angiotensin-aldosterone system. Agents such as omapatrilat combined neprilysin and ACE inhibition but had increased rates of angioedema. Goals of an improved safety profile provided the rationale for the development of the ARNi LCZ696. Along with significant reductions in mortality and hospitalizations, clinical trials suggest that LCZ696 may improve surrogate markers of HF severity. In this paper, we review the preclinical and clinical data that led to the development of LCZ696, the understanding of the underlying mechanistic action, and the robust clinical impact that LCZ696 may have in the near future.
SubjectAngiotensin receptor neprilysin inhibition
Angiotensin-Converting Enzyme Inhibitors
Published Version (Please cite this version)10.1016/j.cardfail.2015.07.008
Publication InfoBuggey, J; DeVore, Adam David; Mentz, Robert John; & Velazquez, Eric J (2015). Angiotensin receptor neprilysin inhibition in heart failure: mechanistic action and clinical impact. J Card Fail, 21(9). pp. 741-750. 10.1016/j.cardfail.2015.07.008. Retrieved from http://hdl.handle.net/10161/11016.
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Assistant Professor of Medicine
Adam D. DeVore, MD, MHS Dr. DeVore is a cardiologist and Assistant Professor of Medicine in the Department of Medicine, Division of Cardiology, at Duke University School of Medicine. His clinical interests include caring for patients with heart failure, including patients with left ventricular assist devices and heart transplants. He is involved in and leads many studies of patients with heart failure at both Duke University Medical Center and the Duke Clinical Resear
Associate Professor of Medicine
I am a cardiologist with a clinical and research interest in heart failure, including advanced therapies such as cardiac transplantation and mechanical assist devices or “heart pumps." I became a heart failure cardiologist in order to help patients manage their chronic disease over many months and years. I consider myself strongly committed to compassionate patient care with a focus on quality of life and patient preference.My research interests are focused on treating co-morbi
Adjunct Professor in the Department of Medicine
LeadershipEric J. Velazquez, MD, is a Professor of Medicine with tenure at Duke University. As section chief for Cardiovascular Imaging in the Division of Cardiology and director of the Cardiac Diagnostic Unit and Echocardiography Laboratories for Duke University Health System, he coordinates a high-volume enterprise and an outstanding group of clinician-investigators and clinical staff who make important contributions across patient care, research and educational
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