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 I
McMurray, John J. V., Packer, Milton, Desai, Akshay S., Gong, Jim, Lefkowitz, Martin P., Rizkala, Adel R., Rouleau, Jean L., Shi, Victor C., Solomon, Scott D., Swedberg, Karl and Zile, Michael R.. (2013) 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 I. European Journal of Heart Failure. 15(9), pp. 1062 - 1073. https://doi.org/10.1093/eurjhf/hft052
|Authors||McMurray, John J. V., Packer, Milton, Desai, Akshay S., Gong, Jim, Lefkowitz, Martin P., Rizkala, Adel R., Rouleau, Jean L., Shi, Victor C., Solomon, Scott D., Swedberg, Karl and Zile, Michael R.|
Aims: Although the focus of therapeutic intervention has been on neurohormonal pathways thought to be harmful in heart failure (HF), such as the renin–angiotensin–aldosterone 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. Methods: Patients with chronic HF, NYHA class II–IV symptoms, an elevated plasma BNP or NT-proBNP level, and an LVEF of ≤40% were enrolled in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortailty and morbidity in Heart Failure trial (PARADIGM-HF). Patients entered a single-blind enalapril run-in period (titrated to 10 mg b.i.d.), followed by an LCZ696 run-in period (100 mg titrated to 200 mg b.i.d.). A total of 8436 patients tolerating both periods were randomized 1:1 to either enalapril 10 mg b.i.d. or LCZ696 200 mg b.i.d. The primary outcome is the composite of cardiovascular death or HF hospitalization, although the trial is powered to detect a 15% relative risk reduction in cardiovascular death. Perspectives: PARADIGM-HF will determine the place of the ARNI LCZ696 as an alternative to enalapril in patients with systolic HF. PARADIGM-HF may change our approach to neurohormonal modulation in HF.
|Keywords||chronic heart failure; renin–angiotensin; ACE inhibitor; angiotensin receptor blocker; natriuretic peptides; neprilysin; neutral endopeptidase; angiotensin receptor neprilysin inhibitor; LCZ696|
|Journal||European Journal of Heart Failure|
|Journal citation||15 (9), pp. 1062 - 1073|
|Publisher||John Wiley and Sons Ltd|
|Digital Object Identifier (DOI)||https://doi.org/10.1093/eurjhf/hft052|
|Open access||Open access|
|Page range||1062 - 1073|
|Research Group||Mary MacKillop Institute for Health Research|
© The Author 2012. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/3.0/), which permits noncommercial reuse, distribution, and reproduction in any medium, provided that the original authorship is properly and fully attributed; the Journal, Learned Society and Oxford University Press are attributed as the original place of publication with correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact email@example.com.
|Place of publication||United Kingdom|
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