Effects of Angiotensin Receptor/Neprilysin Inhibitor Therapy on Amino-terminal Pro-B-Type Natriuretic Peptide and Cardiac Remodeling in Heart Failure with Reduced Ejection Fraction: The PROVE-HF Study

Background In patients with HFrEF, sacubitril/valsartan (sac/val) treatment improves outcomes although uncertainties regarding its mechanism of benefit exist. Reduction in NT-proBNP during HFrEF treatment is associated with reverse cardiac remodeling however such data during treatment with sac/val are lacking. Methods We performed a prospective, 12 month, open-label, single-arm trial of 794 patients initiated on sac/val at 78 outpatient sites. After ACEi/ARB discontinuation, sac/val was initiated and titrated, and blood samples were obtained for NT-proBNP measurement. Echocardiograms were performed at baseline, 6 months, and 12 months and interpreted by a temporally-blinded core lab. The primary endpoint was correlation between change in NT-proBNP concentrations and change in LVEF, LVEDVi, LVESVi, LAVi or E/E' ratio at 12 months. Other objectives included change in these measures at 6 months, and outcome assessment relative to change in NT-proBNP and LVESVi. Results The mean age of study patients was 65.1 years, 28.5% were women and 22.7% were Black. Participants had a baseline LVEF of 28.9%, LVEDVi of 90.1 mL/m2, LVESVi of 64.9 mL/m2, LAVi of 39.7 mL/m2, and E/E' ratio of 13.4. Following sac/val initiation, highly significant early and sustained NT-proBNP reduction was observed. Change in NT-proBNP at 12 months correlated with increased LVEF (r = -0.381; P Conclusions Among patients with HFrEF, reduction in NT-proBNP following initiation of sac/val is associated with significant reverse cardiac remodeling and fewer events, especially in those with greater reduction in NT-proBNP and LVESVi (NCT02887183).