LCZ696 (Angiotensin–Neprilysin Inhibition): The New Kid on the Heart Failure Block?

Angiotensin-converting enzyme inhibitors (ACEIs) have been the cornerstone in systolic heart failure (HF) regimens over the past 25 years. Their ability to block the renin–angiotensin–aldosterone system and their vasodilatory properties has repeatedly been shown to lower morbidity and mortality in patients with HF having reduced ejection fractions. In August 2014, the New England Journal of Medicine published a large trial studying a novel LCZ696 (angiotensin–neprilysin inhibition) agent against enalapril, an ACEI. In the phase III trial, LCZ696 demonstrated superiority to enalapril in composite death from cardiovascular causes and hospitalization for HF. The trial was stopped early due to overwhelming benefit of the study agent. This article provides an extensive review of the mechanism of action, pharmacokinetic properties, clinical efficacy, safety, and tolerability of LCZ696.