Although dis- cussion of hospital-based initiation of sacubitril/valsartan is outside of the scope of this document, it is important to prioritize ongoing titration of GDMT for patients during the hospital-to-home transition. The PIONEER-HF (Compari- son of Sacubitril Valsartan versus Enalapril on Effect on NT-proBNP in Patients Stabilized from an Acute HF Episode) trial established that the initiation of ARNI during an acute decompensated HF hospitalization is feasible (23) after the patient has been hemodynamically stabilized; in PIONEER-HF, up to 25% of patients developed hypotension when treated with sacubitril/valsartan. Therefore, ensuring patients are not volume-depleted at the time of initiation may help to avoid this issue. Notably, the TRANSITION (Comparison of Pre- and Post-discharge Initiation of LCZ696 Therapy in HFrEF Patients After an Acute Decompensation Event) study demonstrated that about one-half of the patients could achieve the target dose within 10 weeks after in-hospital initiation or soon after discharge (24). Accordingly, following the patient s discharge from the hospital, ongoing efforts toward GDMT optimization (including titration to target doses whenever possible) should continue. Clinicians should be advised that sacubitril/valsartan may exert a more noteworthy effect on blood pressure when compared with ACEIs/ARBs. Therefore, in patients with borderline blood pressure (e.g., systolic blood pressure #100 mm Hg), careful administration and follow-up are advised. In noncongested patients with otherwise stable clinical pro les, empiric modest lowering of loop diuretic agents has been found to miti- gate the hypotensive effects of sacubitril/valsartan. Lastly, although the number of patients in studies of ARNI with chronic HFrEF and NYHA class IV symptoms is limited, sacubitril/valsartan remains indicated in this higher-risk population; the role of sacubitril/ valsartan in more advanced forms of HFrEF continues to be explored (25). 5.1.3. 