J A key therapy among African Americans with HFrEF is HYD/ISDN. However, the combined bene t of HYD/ISDN with an ARNI, SGLT2 inhibitor, and/or ivabradine is less clear nevertheless, this lack of clarity should not prevent prescription of these new medications. African Americans are underprescribed HYD/ISDN, a treatment with survival bene ts isolated to those of self-de ned African-Amer- ican race; it should be a priority to initiate evidence-based medications in all applicable populations. We recommend consideration of both HYD/ISDN and ARNI prescriptions for African-American patients, with the acknowledgment that both purportedly act via upregulation of cyclic gua- nosine monophosphate (cGMP) pathways and could in- crease the risk of hypotension. Additionally, the risk of angioedema with both ACEIs and ARNIs is higher in African-American patients (136). Clinical guidance for treating HF in African-American patients includes: a. Establish GDMT with an ARNI/ACEI/ARB (ARNI preferred, if possible), a beta-blocker, and an aldoste- rone antagonist; if stable, follow with titration of HYD/ ISDN (starting at a low dose, but aim for doses used in the pivotal randomized trials [Table 1, Figure 3G]). For those with persistent NYHA class III to IV symptoms, titration should proceed with careful blood pressure monitoring and close monitoring of other side effects (e.g., headache, dizziness). (Note: HYD/ISDN are avail- able as a xed-dose combination or as individual medi- cations. The ACC/AHA/HFSA guideline considers either form acceptable in this context.) b. Avoid ARNIs in settings of known or hereditary angioe- dema with ACEIs or ARBs. c. If the heart rate remains above goal in sinus rhythm, ivabradine may be considered; however, given the paucity of data in African Americans, optimize beta- blocker dosing preferentially. d. Use of an SGLT2 inhibitor should also be considered as concomitant treatment for HFrEF in African Americans. 