The role of angiotensin receptor–neprilysin inhibitors in cardiovascular disease—existing evidence,knowledge gaps,and future directions |
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| Authors: | Andrew P Ambrosy Robert J Mentz Mona Fiuzat John GF Cleland Stephen J Greene Christopher M O'Connor John R Teerlink Faiez Zannad Scott D Solomon |
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| Institution: | 1. Division of Cardiology, Duke University Medical Center, Durham, NC, USA;2. Duke Clinical Research Institute, Durham, NC, USA;3. Robertson Centre for Biostatistics and Clinical Trials, University of Glasgow, Glasgow, UK;4. National Heart & Lung Institute, Imperial College, London, UK;5. Inova Heart and Vascular Institute, Falls Church, VA, USA;6. Division of Cardiology, University of California San Francisco and Section of Cardiology, San Francisco, CA, USA;7. Centre d'Investigation Clinique Inserm, CHU, Université de Lorraine, Institut Lorrain du Coeur et des Vaisseaux, Nancy, France;8. Division of Cardiology, Brigham and Women's Hospital, Boston, MA, USA |
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| Abstract: | Although traditional renin–angiotensin system antagonists including angiotensin‐converting enzyme inhibitors and angiotensin receptor blockers have revolutionized the treatment of cardiovascular disease (CVD), the pivotal PARADIGM‐HF trial demonstrated that sacubitril/valsartan, an angiotensin receptor–neprilysin inhibitor (ARNI), was superior to an angiotensin‐converting enzyme inhibitor in reducing cardiovascular morbidity and mortality in patients with heart failure and reduced ejection fraction. 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–angiotensin 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. |
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| Keywords: | Heart failure Reduced ejection fraction Angiotensin receptor– neprilysin inhibitor Sacubitril/valsartan |
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