Abstract
BACKGROUND: Treatment with sacubitril-valsartan reduces mortality and heart failure (HF) events in HF with reduced ejection fraction and may reduce HF hospitalization in women with HF with preserved ejection fraction. METHODS: EVALUATE-HF randomized 464 participants (109 women) with HF with reduced ejection fraction to sacubitril-valsartan or enalapril for 12 weeks. Documented left ventricular ejection fraction (LVEF) ≤0.40 within the prior 12 months was required, although core laboratory LVEF>0.40 was permitted. Assessments of aortic stiffness (pulse pressure and characteristic impedance, Z(c)) were performed at baseline and at trough and 4 hours postdose at weeks 4 and 12. RESULTS: In models of change from baseline adjusted for baseline value, treatment with sacubitril-valsartan produced greater overall reductions in mean arterial pressure (treatment group difference, -3.0±0.8 mm Hg, P<0.001) and pulse pressure (-3.0±0.8 mm Hg, P<0.001). Postdose reductions in Z(c) were greater in the sacubitril-valsartan group (-16±6 dyne×second/cm(5), P=0.012). Post hoc analyses found evidence of effect modification by LVEF (interaction P=0.036). With LVEF<0.40, postdose reductions in Z(c) were greater in the sacubitril-valsartan group (trough, -3±8 dyne×second/cm(5) versus post-dose, -17±8 dyne×second/cm(5); interaction P=0.024) with no sex difference (treatment×sex interaction, P=0.3). With LVEF≥0.40, treatment with sacubitril-valsartan was associated with greater overall reductions in Z(c) in women (women, -80±21 dyne×second/cm(5) versus men, -20±13 dyne×second/cm(5); interaction P=0.019). CONCLUSIONS: In prespecified analyses that include pre- and postdose assessments at 4 and 12 weeks, treatment with sacubitril-valsartan was associated with greater postdose reductions in aortic Z(c). In a post hoc analysis, sacubitril-valsartan was associated with sustained reductions in Z(c) in women with LVEF≥0.40. Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT02874794.