Drugs Commonly Used for Stage C HFrEF Drug Initial Daily Dose(s) Maximum Dose(s) Mean Doses Achieved in Clinical Trials ACE inhibitors Fosinopril 5 to 10 mg once 40 mg once N/A Perindopril 2 mg once 8 to 16 mg once N/A Quinapril 5 mg twice 20 mg twice N/A Ramipril 1.25 to 2.5 mg once 10 mg once N/A Trandolapril 1 mg once 4 mg once N/A ARBs Aldosterone antagonists Spironolactone 12.5 to 25.0 mg once 25 mg once or twice 26 mg/d (181) Eplerenone 25 mg once 50 mg once 42.6 mg/d (184) Beta blockers Bisoprolol 1.25 mg once 10 mg once 8.6 mg/d (185) Carvedilol 3.125 mg twice 50 mg twice 37 mg/d (186) Carvedilol CR 10 mg once 80 mg once N/A Metoprolol succinate extended release (metoprolol CR/XL) Hydralazine and isosorbide dinitrate Fixed-dose combination (180) 37.5 mg hydralazine/20 mg isosorbide dinitrate 3 times daily 75 mg hydralazine/40 mg isosorbide dinitrate 3 times daily isosorbide dinitrate daily Hydralazine and isosorbide daily and isosorbide dinitrate: 20 to Hydralazine: 300 mg daily in divided doses and isosorbide dinitrate: 120 mg daily in divided doses N/A ACE indicates angiotensin-converting enzyme; ARB, angiotensin-receptor blocker; CR, controlled release; CR/XL, controlled release/extended release; HFrEF, heart failure with reduced ejection fraction; and N/A, not applicable. Table 12. Drug Dosing for Aldosterone Receptor Antagonists Eplerenone Spironolactone Initial dose (only if K 5 mEq/L) 25 mg once daily 25 mg once every other day 12.5 to 25.0 mg once daily 12.5 mg once daily or every other day Maintenance dose (after 4 wk for K 50 mg once daily 25 mg once daily 25 mg once or twice daily 12.5 to 25.0 mg once daily *After dose initiation for K , increase6.0 mEq/L, or worsening renal function, hold until K <5.0 mEq/L. 