The Role of Neprilysin Inhibitors in Cardiovascular Disease
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Heart failure affects over five million Americans each year and contributes to morbidity, mortality, and high health care costs. Despite the benefits of RAAS and SNS blockers, 5-year survival rates in patients with heart failure remain low, necessitating continued research and new drug targets. LCZ696 (sacubitril/valsartan) is an angiotensin-receptor neprilysin inhibitor recently approved for HFrEF, with dual actions that result in enhancement of natriuretic peptide levels and blockade of angiotensin II activities. This drug shows promise in further improving clinical outcomes in HFrEF and is being studied in patients with HFpEF. In the PARADIGM-HF study, LCZ696 (sacubitril/valsartan) was shown to reduce the composite of cardiovascular mortality and heart failure hospitalizations compared with enalapril in patients with HFrEF taking guideline-directed medical therapies and resulted in prolonged survival. In trials, hypotension occurred more frequently with LCZ696 (sacubitril/valsartan) compared to an ACE inhibitor, warranting careful dose titration. Further clinical experience with LCZ696 (sacubitril/valsartan) will provide additional information on tolerability in a broad range of patients of various demographics.
KeywordsHeart failure HFrEF HFpEF Cardiovascular mortality Neprilysin inhibitor Natriuretic peptide levels Angiotension II
Compliance with Ethical Standards
Conflict of Interest
Jared Mills declares that he has no competing interests.
Orly Vardeny has received consulting honoraria from Novartis.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
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