When making a recommendation to initiate an ARNI (either as a switch or as de novo treatment), the Writing Committee recommends the decision occurs within a Dose Adjustments of Sacubitril/Valsartan for Speci c Patient Populations Population Initial Dose High-dose ACEI > Enalapril 10-mg total daily dose or therapeutically equivalent dose of another ACEI twice daily High-dose ARB > Valsartan 160-mg total daily dose or therapeutically equivalent dose of another ARB De novo initiation of ARNI 24/26 mg twice daily Low- or medium-dose ACEI # Enalapril 10-mg total daily dose or therapeutically equivalent dose of another ACEI Low- or medium-dose ARB # Valsartan 160-mg total daily dose or therapeutically equivalent dose of another ARB ACEI/ARB naive Severe renal impairment* ) Moderate hepatic impairment (Child-Pugh Class B) Elderly (age $75 years) *This population was not studied in the PARADIGM-HF trial. The statement is consistent with FDA-approved labeling indications. ACEI angiotensin-converting enzyme inhibitor; ARB angiotensin receptor blocker; ARNI angiotensin receptor-neprilysin inhibitor; eGFR estimated glomerular ltration rate; FDA Food and Drug Administration; PARADIGM-HF Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in HF. Maddox et al. J framework of shared decision-making (https://www. cardiosmart.org/topics/heart-failure/assets/decision-aid/ drug-options-for-patients-with-heart-failure). The writing committee is aware that an ARNI may not be easily accessible to all patients with HFrEF due to challenges with payer coverage and unaffordable copays. Although an ARNI is the preferred renin-angiotensin antagonist in HFrEF, an ACEI/ARB should be used to reduce morbidity and mortality in patients with HFrEF in such cases where the decision is not to use an ARNI. Heart rate independently predicts outcomes in HFrEF. A meta-analysis of beta-blocker trials suggests that heart rate lowering is directly related to improved outcomes (27). A dose-response relationship for evidence-based beta-blockers used in HFrEF has been demonstrated (i.e.