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Title: Hemodynamic Effects of Sacubitril-Valsartan Versus Enalapril in Patients With Heart Failure in the EVALUATE-HF Study: Effect Modification by Left Ventricular Ejection Fraction and Sex. Author: Mitchell GF, Solomon SD, Shah AM, Claggett BL, Fang JC, Izzo J, Abbas CA, Desai AS, EVALUATE-HF Investigators*. Journal: Circ Heart Fail; 2021 Mar; 14(3):e007891. PubMed ID: 33663237. 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, Zc) 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 Zc were greater in the sacubitril-valsartan group (-16±6 dyne×second/cm5, P=0.012). Post hoc analyses found evidence of effect modification by LVEF (interaction P=0.036). With LVEF<0.40, postdose reductions in Zc were greater in the sacubitril-valsartan group (trough, -3±8 dyne×second/cm5 versus post-dose, -17±8 dyne×second/cm5; 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 Zc in women (women, -80±21 dyne×second/cm5 versus men, -20±13 dyne×second/cm5; 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 Zc. In a post hoc analysis, sacubitril-valsartan was associated with sustained reductions in Zc in women with LVEF≥0.40. Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT02874794.[Abstract] [Full Text] [Related] [New Search]