Lege Artis Medicinae

[Paradigm shift in the drug therapy of HFrEF]

HEPP Tamás1, VARJAS Norbert1, BENCZÚR Béla1

SEPTEMBER 16, 2021

Lege Artis Medicinae - 2021;31(08-09)

DOI: https://doi.org/10.33616/lam.31.023

Review

[The incidence and prevalence of heart failure (HF) is constantly increasing, its mor­bidity and mortality are still high, thus the disease burden is huge and its proper treatment is of paramount importance. Subs­tantial evidence on improving its prognosis remains available only by the treatment of chronic heart failure with reduced left ventricular function (HFrEF). There have been published a number of “milestone” studies in the last decades, the results of which fundamentally determined the HF therapy until recently. Baseline therapy for HFrEF has been placed on three pillars for a long time: angiotensin-converting-en­zyme inhibitors (ACEI), beta-blocker (BB), and mi­ne­ralocorticoid receptor antagonist (MRA) are included in different heart failure guide­lines with I/A level recommendation. The ground-breaking highly important PARADIGM-HF study was published in 2014, and examined an entirely new class of drugs, the sacubitril/valsartan, which belongs to the group of angiotensin receptor blocking/neprilysin inhibitors (ARNI) in HFrEF patients. Results of this study showed that sacubitril/valsartan significantly reduced the primary composite endpoint of CV mortality and HF hospitalization by 20% and reduced overall mortality by 16% compared to an active comparator enalapril, which has the broadest evidence in HFrEF therapy. The 2016 European Society of Cardiology (ESC) HF guidelines recommended the use of sacubitril/valsartan with an I/B evidence level as a replacement for an ACEI to further reducing the risk of HF hospitalization and death of out-patients with HFrEF who remained symptomatic despite optimal treatment with an ACEI, a BB and an MRA. Later, several smaller studies concerned sacubitril/valsartan with slightly different indications and in other patient groups. The PIONEER-HF study demonstrated that early initiation of sacubitril/valsartan therapy after the stabiliza­tion of acute HF is safe and effective in HFrEF patients, reduces more rapidly the NT-proBNP levels - which correlates with HF prognosis -, than the enalapril. The TRANSITION and TITRATION studies provided useful information on the initiation of sacubitril/valsartan therapy and the strategy of dose titration. The appearance of sacubitril/valsartan opened a new era in HFrEF therapy a few years ago, an era we are actually experiencing in Hungary. Thanks to SGLT-2 inhibitors, it is also possible that we are at the door of an even newer therapeutic era. This question is expected to be answered in the new ESC HF-guidelines to be published soon this year. ]

AFFILIATIONS

  1. Tolna Megyei Balassa János Kórház, I. Belgyógyászat,

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