Desai AS, Solomon SD, Shah AM, et al. - Through a randomized clinical trial of 464 participants with heart failure and reduced ejection fraction (HFrEF), researchers ascertained whether treatment of HFrEF with sacubitril-valsartan enhanced central aortic stiffness and cardiac remodeling in comparison with enalapril. At 12 weeks, aortic characteristic impedance reduced from 223.8 to 218.9 dyne × s/cm⁵ in the sacubitril-valsartan group and rose from 213.2 to 214.4 dyne × s/cm⁵ in the enalapril group. Of nine prespecified secondary endpoints, no important between-group variation in change from baseline was observed in four, including left ventricular ejection fraction. Nonetheless, greater decreases from baseline were noted with sacubitril-valsartan vs enalapril in all others, including left atrial volume, left ventricular end-systolic and end-diastolic volume indexes, and mitral E/e′ ratio. In both groups, rates of adverse events including hypotension were comparable. Thus, the treatment of HFrEF with sacubitril-valsartan, in comparison with enalapril, did not significantly decrease central aortic stiffness. Moreover, the study conclusions may give insight into mechanisms underlying the impacts of sacubitril-valsartan in HFrEF.