In patients with acute decompensated heart failure (HF), treatment with the angiotensin receptor–neprilysin inhibitor sacubitril–valsartan is safe and results in greater reduction in the plasma levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) than treatment with the angiotensin-converting enzyme inhibitor enalapril. These results from the PIONEER-HF trial, presented at the AHA Scientific Sessions 2018, support the in-hospital initiation of sacubitril─valsartan therapy in patients with acute HF.
In 2015, the FDA approved the use of sacubitril─valsartan for the treatment of patients with chronic HF, after data from the PARADIGM-HF trial showed that this therapy led to greater reductions in cardiovascular deaths and HF-related hospitalizations in these patients than enalapril therapy. Patients with acute HF were excluded from the PARADIGM-HF trial, and the multicentre, double-blind PIONEER-HF trial was designed to investigate the effects of the drug in the context of acute HF.
A total of 881 patients who were hospitalized for acute decompensated HF were randomly assigned after haemodynamic stabilization to receive sacubitril–valsartan or enalapril. The primary efficacy outcome, defined as the time-averaged change in plasma levels of NT-proBNP from baseline to weeks 4 and 8, was –46.7% in the sacubitril–valsartan group and –25.3% in the enalapril group (HR 0.71, 95% CI 0.63─0.81; P < 0.001). Safety outcomes, such as rates of worsening renal function or hyperkalaemia, were similar between the two groups.
These results extend the findings of the PARADIGM-HF trial to an inpatient setting. However, NT-proBNP levels were used as a surrogate; therefore, a trial to confirm the effect of the drug on cardiovascular outcomes is warranted.
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Original article
Velazquez, E. J. et al. Angiotensin–neprilysin inhibition in acute decompensated heart failure. N. Engl. J. Med. https://doi.org/10.1056/NEJMoa1812851 (2018)
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Le Bras, A. Safety and efficacy of sacubitril─valsartan in acute heart failure. Nat Rev Cardiol 16, 4 (2019). https://doi.org/10.1038/s41569-018-0134-5
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DOI: https://doi.org/10.1038/s41569-018-0134-5