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Sacubitril/valsartan and circulating neprilysin hypothesis in patients with HFpEF

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Neprilysin serum levels (sNEP) exhibited significant prognostic value in patients with heart failure (HF). In the PARADIGM-HF study benefit of sacubitril/valsartan was observed in patients with reduced ejection fraction (HFrEF),… Click to show full abstract

Neprilysin serum levels (sNEP) exhibited significant prognostic value in patients with heart failure (HF). In the PARADIGM-HF study benefit of sacubitril/valsartan was observed in patients with reduced ejection fraction (HFrEF), while in the PARAGON-HF benefit was only observed in the subgroup of patients with LVEF <57%. To assess the prognostic value of sNEP in ambulatory patients with HF and preserved ejection fraction (HFpEF) and LVEF >57% (group 1), in comparison with patients with LVEF ≤57% (group 2). Consecutive patients with HF attended at the Unit from May 2006 to February 2016 were considered for the study. The primary end-point was the composite of cardiovascular death or HF hospitalization. All-cause death, cardiovascular death, HF hospitalization and the composite of all-cause death or HF hospitalization were secondary end-points. Competing risk methods (R package by Bob Gray for SPSS) were used when required. sNEP was measured in 1428 patients (age 67.7±12.7, 70.3% men, LVEF 35.8% ±14, 48.9% from ischemic etiology), 144 of which had a LVEF >57% (age 70.1±15, 43.8% men, 53.5% from hypertensive or valvular etiologies). sNEP levels did not significantly differ between the two groups of patients (p=0.31). During a mean follow-up of 6±3.9 years, 856 deaths were recorded (459 from cardiovascular causes) and 523 patients suffered at least one HF hospitalization. The primary end-point occurred in 941 patients (in 111 of the 144 patients with LVEF >57%). Table 1 shows sNEP age- and sex-adjusted hazard ratios for the primary and secondary end-points. sNEP prognostic value in patients with HFpEF and LVEF >57% outperforms that observed in patients with lower LVEF. These data support the personalized use of sNEP in identifying HFpEF patients that may benefit from treatment with sacubitril/valsartan. Type of funding source: None

Keywords: death; hospitalization; sacubitril valsartan; end; patients hfpef

Journal Title: European Heart Journal
Year Published: 2020

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