title: The safety of sacubitril-valsartan for the treatment of chronic heart failure.
abstract: Sacubitril-valsartan is a combination drug that contains the neprilysin inhibitor sacubitril and angiotensin II receptor blocker valsartan. In 2015, the US Food and Drug Administration approved sacubitril-valsartan for treatment of heart failure patients with reduced ejection fraction and New York Heart Association class II-IV symptoms following a large, Phase III clinical trial (PARADIGM-HF) that demonstrated a 20% reduction in the combined primary end-point of death from cardiovascular cause or hospitalization for heart failure compared to enalapril. Areas covered: This review discusses the clinical efficacy and safety of angiotensin receptor neprilysin inhibitor sacubitril-valsartan in heart failure with reduced ejection fraction. Expert opinion: Based on the PARADIGM-HF trial, sacubitril-valsartan offers compelling reductions in meaningful clinical endpoints, independent of age or severity of disease. The rate of adverse events was comparable between the enalapril and sacubitril-valsartan groups, although the absolute rates are likely underestimated due to the entry criteria and run-in period. Future trials and post-market surveillance are critical to better understand the risk of angioedema in high risk populations, particularly African-Americans, as well as long-term theoretical risks including the potential for increased cerebral amyloid plaque deposition with possible development of neurocognitive disease. Current trials are underway to evaluate potential benefit in patients with heart failure with preserved ejection fraction.
authors.affiliation: a School of Medicine , University of California San Francisco , San Francisco , CA , USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Tyler
authors.affiliation: a School of Medicine , University of California San Francisco , San Francisco , CA , USA.|b Section of Cardiology , San Francisco Veterans Affairs Medical Center , San Francisco , CA , USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Teerlink
mesh_terms: D000613:Aminobutyrates / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000799:Angioedema / Q000453:epidemiology / Q000209:etiology; D057911:Angiotensin Receptor Antagonists / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001713:Biphenyl Compounds; D002908:Chronic Disease; D004338:Drug Combinations; D004656:Enalapril / Q000009:adverse effects / Q000627:therapeutic use; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D012307:Risk Factors; D013777:Tetrazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000068756:Valsartan
chemical_list: D000613:Aminobutyrates; D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D004338:Drug Combinations; D013777:Tetrazoles; D004656:Enalapril; D000068756:Valsartan; C549068:sacubitril and valsartan sodium hydrate drug combination
keywords: Cardiomyopathy; LCZ696; drug combination; drug safety; heart failure; pharmacology; sacubitril-valsartan