[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. ]
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