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Sacubitril-valsartan (LCZ696) in the treatment of heart failure


Authors: J. Vítovec 1;  L. Špinarová 1;  J. Špinar 2
Authors place of work: I. interní kardioangiologická klinika LF MU a FN u sv. Anny v Brně 1;  Interní kardiologická klinika LF MU a FN Brno 2
Published in the journal: Kardiol Rev Int Med 2016, 18(2): 125-128

Summary

New dual antagonist for receptors for AII (ARB) and neprilysin, generic name sacubitril-valsartan (LZC696) or angiotensin receptor blocker and neprilysin inhibitor (ARNI), was experimentally and clinically tested for the treatment of hypertension and heart failure. The treatment draws on the positive clinical effects of ARB and experimentally proven effects of the inhibition of vasodilatating natriuretic peptide decomposition. In the PARAMOUNT study in patients with heart failure with preserved ejection fraction (HFpEF), LCZ696 reduced NT-pro BNP concentration to a greater extent than did valsartan at 12 weeks and was well tolerated. The PARADIGM-HF study was discontinued early, showing that LCZ696 was clearly superior to enalapril, with a 20% reduction of the risk of death and hospitalisation for heart failure. PARAGON-HF will assess the effect of LCZ696 on the outcomes concerning cardiovascular death and total –  first and recurrent –  HF hospitalisations in patients with HFpEF.

Keywords:
enalapril –  neprilysin –  heart failure –  sacubitril-valsartan – LCZ696 –  valsartan


Zdroje

1. Vítovec J, Špinar J, Špinarová L. Inhibice systému renin-angiotensin-aldosteron u srdečního selhání aneb od obecného souhlasu (CONSENSUS) po vzorec myšlení (PARADIGM-HF). Vnitř Lék 2015; 61: 470– 474.

2. Špinarová L, Špinar J, Vítovec J. Léčba natriuretickými peptidy –  konec mýtu? Remedia 2011; 21: 78– 81.

3. Gu J, Noe A, Chandra P et al. Pharmacokinetics and pharmacodynamics of LCZ696, a novel dualact­ing angiotensin receptor-neprilysin inhibitor (ARNI). J Clin Pharmacol 2010; 50: 401– 414. doi: 10.1177/ 0091270009343932.

4. Bavishi C, Mes­serli FH, Kadosh B et al. Role of Neprilysin inhibitor combinations in hypertension: insights from hypertension and heart fail­ure trials. Eur Heart J 2015; 36: 1967– 1973. doi: 10.1093/ eurheartj/ ehv142.

5. Packer M, Califf RM, Konstam MA et al. Comparison of omapatrilat and enalapril in patients with chronic heart failure: the Omapatrilat versus Enalapril Randomized Trial of Utility in Reduc­ing Events (OVERTURE). Circulation 2002; 106: 920– 926.

6. Mes­serli FH, Nus­sberger J. Vasopeptidase inhibition and angio-oedema. Lancet 2000; 356: 608– 609.

7. Segura J, Ruilope LM. Dual-act­ing angiotensin receptor-neprilysin inhibition. Curr Hypertens Rep 2011; 13: 74– 78. doi: 10.1007/ s11906-010-0166-7.

8. Solomon SD, Zile M, Pieske B et al. The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: a phase 2 double-blind randomised control­led trial. Lancet 2012; 380: 1387– 1395. doi: 10.1016/ S0140-6736(12)61227-6.

9. McMur­ray JJ, Packer M, Desai AS et al. The PARADIGM-HF Investigators and Com­mittees. Angiotensin- neprilysin inhibition versus enalapril in heart failure. N Engl J Med 2014; 371: 993– 1004. doi: 10.1056/ NEJMoa1409077.

10. Špinarová L, Špinar J, Vítovec J. Co přináší studie PARADIGM? Kardiol Rev Int Med 2014; 16: 395– 397.

11. Solomon SD, McMur­ray JJ, Gong J et al. Long term ef­ficacy and safety comparison of the angiotensin receptor neprilysin inhibitor (ARNi), LCZ696, and valsartan, in patients with heart failure and preserved ejection fraction: a randomized, double blind, morbidity and mortality trial Prospective comparison of ARni with Arb Global Outcomes in heart failure with preserved ejectioN fraction (PARAGON-HF). Lancet 2012; 380: 1387– 1395. doi: 10.1016/ S0140-6736(12)61227-6.

Štítky
Paediatric cardiology Internal medicine Cardiac surgery Cardiology
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