Does Neprilysin Inhibition Potentiate or Minimize the Adverse Effects of Glucagon-Like Peptide-1 Receptor Agonists in Chronic Heart Failure?

Abstract

Heart failure and diabetes commonly coexist, and therefore, drugs that favorably influence the natural history of each of these two disorders are likely to be prescribed together. 1 Packer M. Activation and inhibition of sodium-hydrogen exchanger is a mechanism that links the pathophysiology and treatment of diabetes mellitus with that of heart failure. Circulation. 2017; 136: 1548-1559 Crossref PubMed Scopus (138) Google Scholar In patients with type 2 diabetes, glucagon-like peptide-1 (GLP-1) receptor agonists decrease the risk of major adverse cardiovascular events, 2 Marso S.P. Daniels G.H. Brown-Frandsen K. Kristensen P. Mann J.F. Nauck M.A. et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016; 375: 311-322 Crossref PubMed Scopus (4190) Google Scholar , 3 Marso S.P. Bain S.C. Consoli A. Eliaschewitz F.G. Jódar E. Leiter L.A. et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016; 375: 1834-1844 Crossref PubMed Scopus (2977) Google Scholar and liraglutide is approved to reduce cardiovascular death, nonfatal myocardial infarction and nonfatal stroke. 4 Tucker M.E. FDA grants liraglutide cardiovascular events indication. https://www.medscape.com/viewarticle/884726Date: 2017 Date accessed: November 12, 2017 Google Scholar Analogously, in patients with chronic heart failure and a reduced ejection fraction, neprilysin inhibition has been shown to decrease the risk of cardiovascular death and hospitalization for heart failure, 5 McMurray J.J. Packer M. Desai A.S. Gong J. Lefkowitz M.P. Rizkala A.R. et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014; 371: 993-1004 Crossref PubMed Scopus (3899) Google Scholar and sacubitril/valsartan is approved to reduce cardiovascular morbidity and mortality. Since the shared goal of treating diabetes and heart failure is to minimize the occurrence of life-threatening cardiovascular events, it is likely that physicians will be prescribing GLP-1 receptor agonists and neprilysin inhibitors concurrently in the same patients.