Neprilysin/therapeutic use

IJCS

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PARAGON-HF: Lessons Learned and Perspectives

José Francisco Kerr Saraiva et al. Isadora de Oliveira

An estimated 6.5 million Americans aged 20 and over have heart failure (HF) and projections show that the prevalence of HF will increase by 46% from 2012 to 2030, resulting in over 8 million people with HF.

Patients with HF can be stratified into different categories of left ventricular ejection fraction (LVEF), presenting different phenotypes in terms of demographics, clinical presentation, etiology and outcomes. The current classification comprises HF with reduced ejection fraction (EF) [EF ≤ 40% (HFrEF)], with intermediate EF [EF 40-50% (HFiEF), and preserved EF [EF ≥ 50% (HFpEF).^,

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Paradigm-HF: a Paradigm Shift in Heart Failure Treatment?

Luis Cláudio Lemos Correia et al. Anis Rassi Jr.

The tested concept

Although LCZ696 appears to be the name of a newly invented molecule, it is not exactly that. In fact, it is a mixture of 320 mg of traditional valsartan with sacubitril. Sacubitril is the new drug, which acts by inhibiting neprilysin action. Neprilysin degrades “good” molecules, such as the natriuretic peptide and bradykinin. Therefore, by inhibiting neprilysin, sacubitril increases the concentration of these molecules, which have vasodilating and natriuretic action. Therefore, the burden of proof is on the clinical benefit of sacubitril. Surprisingly, this was not the concept tested in PARADIGM-HF trial.

What has been done in the PARADIGM-HF trial? The standard treatment of the sacubitril group was curiously more appropriate than the standard treatment in the control group. While the sacubitril group patients enjoyed a blockade of the renin-angiotensin-aldosterone system determined by a maximum dose of valsartan (320 mg daily), in the control group patients were given half of the maximum dose of enalapril (20 mg daily, fixed dose).

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PARAGON-HF: Lessons Learned and Perspectives

Paradigm-HF: a Paradigm Shift in Heart Failure Treatment?

The tested concept

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Electronic Document Format (Vancouver)

Electronic Document Format (ABNT)

Electronic Document Format (APA)

Electronic Document Format (ISO)