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Focus on the Novel Cardiovascular Drug LZC696: from Evidence to Clinical Consideration

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Abstract

LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor (ARNI), is comprised of the angiotensin receptor blocker valsartan and the neprilysin inhibitor pro-drug sacubitril (AHU377). After oral administration, AHU377 is rapidly metabolized to the active neprilysin inhibitor LBQ657. LCZ696 exerts its effects of diuresis, natriuresis, vasodilation and aldosterone secretion inhibition through simultaneous renin-angiotensin-aldosterone system (RAAS) blockade and natriuretic peptides system (NPS) enhancement. Powerful evidence including PARAMETER and PRARDIGM-HF trials have shown that LCZ696 outperforms RAAS inhibition in treating patients with hypertension and heart failure with reduced ejection fraction (HFrEF), and is well tolerated. In addition, accumulating evidence also suggests its potential use in heart failure with preserved ejection fraction (HFpEF), chronic kidney disease (CKD), post-myocardium infarction (post-MI) and stroke. Both the FDA and CHMP have approved LCZ696 for treatment of HFrEF. Despite all this, some special issues (e.g. use in specific subgroups, adverse events, contraindications and cost-effectiveness analysis) should be considered before its implementation in clinical practice.

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  1. Department of Cardiology, Affiliated Hospital of Putian University, Putian, Fujian, China

    L. M. Lin, Y. Wu & M. F. Wu

  2. Department of Cardiology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China

    J. X. Lin

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We confirm that there is no funding support in this manuscript and that we did not receive any support from the sponsor Novartis. We declare that we are the sole authors of the manuscript and the article was not written by any agency or bureau with any external financial support.

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This article does not contain studies with human participants or animals performed by any of the authors.

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L. M. Lin and M. F. Wu contributed equally to this article.

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Lin, L.M., Wu, Y., Wu, M.F. et al. Focus on the Novel Cardiovascular Drug LZC696: from Evidence to Clinical Consideration. Cardiovasc Drugs Ther 30, 623–633 (2016). https://doi.org/10.1007/s10557-016-6699-5

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