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However, despite international regulatory approval and strong recommendations in the guidelines, uptake of sacubitril\/valsartan has been disappointing. Sacubitril\/valsartan is now the focus of a large programme of clinical trials testing the hypothesis that ARNIs may supplant conventional renin\u2013angiotensin system inhibitors across the spectrum of CVD, including hypertension, secondary prevention after myocardial infarction, and heart failure with preserved ejection fraction. This review summarizes the existing evidence, knowledge gaps, and future directions of ARNIs in CVD based on discussions between clinical trialists, industry representatives, and regulatory authorities at the 2016 Global CardioVascular Clinical Trialists Forum in Washington, D.C.<\/jats:p>","DOI":"10.1002\/ejhf.1159","type":"journal-article","created":{"date-parts":[[2018,2,21]],"date-time":"2018-02-21T15:28:29Z","timestamp":1519226909000},"page":"963-972","source":"Crossref","is-referenced-by-count":40,"title":["The Role of Angiotensin Receptor\u2013Neprilysin Inhibitors in Cardiovascular Disease\u2014Existing Evidence, Knowledge Gaps, and Future Directions"],"prefix":"10.1093","volume":"20","author":[{"given":"Andrew P.","family":"Ambrosy","sequence":"first","affiliation":[{"name":"Division of Cardiology, Duke University Medical Center , Durham, NC ,","place":["USA"]},{"name":"Duke Clinical Research Institute , Durham, NC ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Mentz","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Duke University Medical Center , Durham, NC ,","place":["USA"]},{"name":"Duke Clinical Research Institute , Durham, NC ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Fiuzat","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute , Durham, NC ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G.F.","family":"Cleland","sequence":"additional","affiliation":[{"name":"Robertson Centre for Biostatistics and Clinical Trials, University of Glasgow , Glasgow ,","place":["UK"]},{"name":"National Heart & Lung Institute, Imperial College , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen 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