Study PARADIGM-HF – a paradigm shift in the treatment of chronic heart failure


Authors: doc. MUDr. Jan Bělohlávek, Ph.D.
Authors‘ workplace: Národní koordinátor studie PARADIGM-HF v České republice
Published in: Čas. Lék. čes. 2015; 154: 269-271
Category: Review Article

McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR; PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med 2014; 371(11): 993–1004.

Overview

Chronic heart failure is a crucial problem of current cardiology. Despite that, no major development has occurred in the therapy in recent years. In this regard, first results of studies with ARNI inhibitors (angiotensin-receptor neprilysin inhibitors) may be considered hopeful. Dual inhibition of AT1 receptors and neprilysin blocks renin-angiotensin-aldosteron (RAS) axis and concurrently supports natural vasodilatory and diuretic effect of natriuretic peptides. Large-scale prospective randomized multicenter trial PARADIGM-HF with more than 8000 individuals with stabilized chronic heart failure with systolic dysfunction (LV EF ≤ 40%, later ≤ 35%), mostly in functional class NYHA II–III with elevated BNP/NT-pro BNP has shown 20% decrease in primary endpoint (cardiovascular death or hospitalization for heart failure) in a group treated by ARNI (LCZ696; sacubiltril – valsartan). Beneficial effect of ARNI was consistent also for total and cardiovascular mortality, for hospitalization for heart failure and in other pre-specified subgroup analyses, including quality of life. The treatment was safe, typical adverse event was hypotension, however without a need to interrupt the treatment. Dual RAS and neprilysin inhibition might thus after long time become a change in stable chronic heart failure with systolic dysfunction treatment „paradigm“. Czech Republic significantly contributed to this study and all study sites should be congratulated and thanked for their high-quality work provided.

Keywords:
chronic heart failure – neprilysin – angiotensin-receptor inhibitors


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