The Role of Neprilysin Inhibitors in Cardiovascular Disease.
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.
['Mills|Jared|J|', 'Vardeny|Orly|O|']
D000613:Aminobutyrates D057911:Angiotensin Receptor Antagonists D001713:Biphenyl Compounds D004338:Drug Combinations D006333:Heart Failure D006801:Humans D015260:Neprilysin D016032:Randomized Controlled Trials as Topic D013777:Tetrazoles D000068756:Valsartan
Neprilysin inhibitor Heart failure HFrEF Natriuretic peptide levels HFpEF Cardiovascular mortality Angiotension II