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The role of angiotensin receptor–neprilysin inhibitors in cardiovascular disease—existing evidence, knowledge gaps, and future directions
Author(s) -
Ambrosy Andrew P.,
Mentz Robert J.,
Fiuzat Mona,
Cleland John G.F.,
Greene Stephen J.,
O'Connor Christopher M.,
Teerlink John R.,
Zannad Faiez,
Solomon Scott D.
Publication year - 2018
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1002/ejhf.1159
Subject(s) - valsartan , sacubitril , medicine , neprilysin , heart failure , ejection fraction , angiotensin receptor , sacubitril, valsartan , myocardial infarction , cardiology , clinical trial , renin–angiotensin system , angiotensin ii , pharmacology , receptor , blood pressure , enzyme , biochemistry , chemistry
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.