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ISSN: 1734-1922
Archives of Medical Science
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vol. 13
Letter to the Editor

The need to apply the best therapy in heart failure – the era after PARADIGM-HF

Malgorzata Lelonek

Arch Med Sci 2017; 13, 5: 1244–1248
Online publish date: 2016/05/05
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About 26 million adults worldwide suffer from heart failure (HF) [1]. However, general public awareness of HF is poor [2]. Despite the improvement in health care over the past 20 years, mortality in patients with HF remains unacceptably high. About 2–17% of patients admitted to hospital die during hospitalization, 17–45% within 1 year of admission and the majority by 5 years from admission [3]. Despite the use of angiotensin-converting enzyme (ACE) inhibitors, -blockers, and mineralocorticoid receptor antagonists (MRA), in HF the endogenous neurohormonal system plays an important role.
The molecular complex of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor (ARNI), combines an angiotensin receptor blocker (valsartan) with a neprilysin inhibitor (sacubitril), and represents an important step in the management of HF and reduced ejection fraction. This dual action places this drug at the center of two critically important systems in HF: the renin–angiotensin–aldosterone system (RAAS), and the natriuretic peptide system (NPS). The mechanism of action for valsartan is well known and for sacubitril is prevention of the catabolism of natriuretic peptides (NPs). Neprilysin (NEP), a neutral endopeptidase, diminishes vasorelaxant, natriuretic, and diuretic actions of NPs beneficial in HF.
Natriuretic peptides exert their effects through binding to their receptors and resulting in the generation of cyclic guanosine monophosphate (cGMP). Cyclic guanosine monophosphate mediates natriuresis and inhibition of renin and aldosterone, and induces vasorelaxant, antifibrotic and antihypertrophic effects [4]. The NPs have a short-lived action due to their rapid metabolism by NEP. Therefore, the use of a substance that blocks the action of NEP, such as a NEP inhibitor (sacubitril), will extend their life, increase their blood levels and consequently increase their effectiveness in the treatment of HF [4].
In the recent Prospective comparison of Angiotensin Receptor neprilysin inhibitor with Angiotensin converting enzyme inhibitors to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF), chronic administration of sacubitril/valsartan (formerly known as LCZ696) was superior to enalapril in reducing death and hospitalizations in patients with chronic HF and a reduced ejection fraction (HFrEF) [5]. The dose of enalapril was selected based on its effect in reducing the risk of death in the SOLVD-T...

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