Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin-converting enzyme inhibition in patients with chronic systolic heart failure: rationale for and design of the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF)

McMurray J. J. V. , Packer M., Desai A. S. , Gong J., Lefkowitz M. P. , Rizkala A. R. , ...More

EUROPEAN JOURNAL OF HEART FAILURE, vol.15, no.9, pp.1062-1073, 2013 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 15 Issue: 9
  • Publication Date: 2013
  • Doi Number: 10.1093/eurjhf/hft052
  • Page Numbers: pp.1062-1073
  • Keywords: Chronic heart failure, Reninangiotensin, ACE inhibitor, Angiotensin receptor blocker, Natriuretic peptides, Neprilysin, Neutral endopeptidase, Angiotensin receptor neprilysin inhibitor, LCZ696, ATRIAL-NATRIURETIC-PEPTIDE, VENTRICULAR EJECTION FRACTIONS, RANDOMIZED-TRIAL, VASOPEPTIDASE INHIBITOR, DOUBLE-BLIND, ENALAPRIL, OMAPATRILAT, VALSARTAN, SURVIVAL, LCZ696


Although the focus of therapeutic intervention has been on neurohormonal pathways thought to be harmful in heart failure (HF), such as the reninangiotensinaldosterone system (RAAS), potentially beneficial counter-regulatory systems are also active in HF. These promote vasodilatation and natriuresis, inhibit abnormal growth, suppress the RAAS and sympathetic nervous system, and augment parasympathetic activity. The best understood of these mediators are the natriuretic peptides which are metabolized by the enzyme neprilysin. LCZ696 belongs to a new class of drugs, the angiotensin receptor neprilysin inhibitors (ARNIs), which both block the RAAS and augment natriuretic peptides.