These results were demon- strated in important subgroups not represented in the PARADIGM-HF trial, such as those with de novo HF or naive to ACEIs/ARBs, those with lower enrollment N-ter- minal pro B-type natriuretic peptide (NT-proBNP) con- centrations, or those not attaining the target dose in the course of the study. The results from PROVE-HF were further substantiated by evidence from the randomized EVALUATE-HF (Effects of Sacubitril/Valsartan vs. Ena- lapril on Aortic Stiffness in Patients With Mild to Moder- ate HF With Reduced Ejection Fraction) trial, which demonstrated an improvement in echocardiographic pa- rameters of reverse cardiac remodeling as early as 12 weeks with treatment of sacubitril/valsartan compared with enalapril (20). A frequent question is whether established use of an aldosterone antagonist is mandatory before initiation of an ARNI. As there is no existing predicate data to suggest an aldosterone antagonist is mandatory before ARNI therapy, lack of treatment with an aldosterone antagonist should not delay initiating or switching a patient to an ARNI. Guidance for the transition from an ACEI or ARB to an ARNI is detailed in Figures 2 and 3 and in Tables 1 to 4. When making the transition from an ACEI to an ARNI, a 36-hour washout period should be strictly observed to avoid angioedema, a delay that is not required when switching from an ARB to an ARNI. In a recent study (21), a comparison between condensed and conservative ap- proaches to initiation of sacubitril/valsartan was explored. The investigators compared titration to a target dose between 3 and 6 weeks. Both approaches were tolerated similarly, but the gradual titration approach maximized attainment of the target dose of sacubitril/ valsartan in patients previously receiving low doses of an ACEI/ARB. 