In light of these developments, an update on when and how to add, switch, and titrate all HFrEF therapies to maximally tolerated, and ideally target, doses (Figure 1, Table 1) was deemed important. Starting and Target Doses of Select GDMT and Novel Therapies for HF (choice and timing of each therapy and in whom they should be added discussed in the text)* Starting Dose Target Dose Beta-Blockers Bisoprolol 1.25 mg once daily 10 mg once daily Carvedilol 3.125 mg twice daily 25 mg twice daily for weight <85 kg and 50 mg twice daily for weight $85 kg Metoprolol succinate 12.5 25 mg daily 200 mg daily ARNIs Sacubitril/valsartan 24/26 mg 49/51 mg twice daily 97/103 mg twice daily ACEIs Enalapril 2.5 mg twice daily 10 20 mg twice daily Lisinopril 2.5 5 mg daily 20 40 mg daily Ramipril 1.25 mg daily 10 mg daily ARBs Candesartan 4 8 mg daily 32 mg daily Losartan 25 50 mg daily 150 mg daily Valsartan 40 mg twice daily 160 mg twice daily Aldosterone antagonists Eplerenone 25 mg daily 50 mg daily Spironolactone 12.5 25 mg daily 25 50 mg daily Dapagli ozin 10 mg daily 10 mg daily Empagli ozin 10 mg daily 10 mg daily Vasodilators Isosorbide dinitrate Fixed-dose combination isosorbide dinitrate/hydralazine Ivabradine Ivabradine 2.5 5 mg twice daily Titrate to heart rate 50 60 beats/min. Maximum dose 7.5 mg twice daily *Digoxin remains indicated for HFrEF, but there are no contemporary data to warrant additional comment in this document. The reader is referred to already available guideline statements (3). Isosorbide mononitrate is not recommended by the ACC/AHA/HFSA guideline. The ACC/AHA/HFSA guideline considers either the xed-dose combination or the separate combination of isosorbide dinitrate and hydralazine as appropriate guideline-directed therapy for HF. 