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The initial development of neprilysin inhibitors, then angiotensin converting enzyme-neprilysin inhibitors and, most recently, the angiotensin receptor neprilysin inhibitor (ARNI) LCZ696 (sacubitril valsartan) as an extension of the nurohumoral basis for the treatment of heart failure is also summarised. Finally, the implications of the compelling benefits of LCZ696 compared with enalapril in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF) is discussed.<\/jats:p>","DOI":"10.1002\/ejhf.250","type":"journal-article","created":{"date-parts":[[2015,3,9]],"date-time":"2015-03-09T03:48:24Z","timestamp":1425872904000},"page":"242-247","source":"Crossref","is-referenced-by-count":112,"title":["Neprilysin Inhibition to Treat Heart Failure: A Tale of Science, Serendipity, and Second Chances"],"prefix":"10.1093","volume":"17","author":[{"given":"John J.V.","family":"McMurray","sequence":"first","affiliation":[{"name":"BHF Cardiovascular Research Centre, University of Glasgow , Glasgow 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