title: Angiotensin-Neprilysin Inhibition as a Paradigm for All?
abstract: Composite angiotensin receptor-neprilysin inhibition (ARNi) represents a novel pharmacologic strategy for treatment of heart failure with reduced ejection fraction (HFrEF). In the PARADIGM-HF (Prospective comparison of ARNi with ACEi to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial of 8399 subjects with HFrEF, treatment with the ARNi LCZ696 (sacubitril/valsartan) was associated with statistically important reductions in cardiovascular death, all-cause mortality, and the composite of cardiovascular death or heart failure hospitalization in comparison with enalapril. These data have supported the US and European regulatory approval of sacubitril/valsartan and guideline-based recommendations for its use in the treatment of selected patients with HFrEF. In this review, we discuss the evidence supporting use of ARNi in preference to angiotensin-converting enzyme-inhibitors or angiotensin receptor blockers in patients with HFrEF and identify a strategy for selection of appropriate patients for transition to ARNi in clinical practice.
authors.affiliation: Advanced Heart Disease Section, Cardiovascular Division, Brigham and Women's Hospital, 75 Francis St., Boston, MA, 02115, USA.
authors.forename: Muthiah
authors.initials: M
authors.lastname: Vaduganathan
authors.affiliation: Advanced Heart Disease Section, Cardiovascular Division, Brigham and Women's Hospital, 75 Francis St., Boston, MA, 02115, USA. adesai@partners.org.
authors.forename: Akshay S
authors.initials: AS
authors.lastname: Desai
mesh_terms: D000613:Aminobutyrates / Q000627:therapeutic use*; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000809:Angiotensins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001713:Biphenyl Compounds; D004338:Drug Combinations; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D006760:Hospitalization; D006801:Humans; D015260:Neprilysin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013318:Stroke Volume / Q000187:drug effects*; D013777:Tetrazoles / Q000627:therapeutic use*; D016896:Treatment Outcome; D000068756:Valsartan
chemical_list: D000613:Aminobutyrates; D057911:Angiotensin Receptor Antagonists; D000809:Angiotensins; D001713:Biphenyl Compounds; D004338:Drug Combinations; D013777:Tetrazoles; D000068756:Valsartan; D015260:Neprilysin; C549068:sacubitril and valsartan sodium hydrate drug combination
keywords: Clinical trials; Heart failure; Neprilysin inhibition; Pharmacotherapy