Drugs known to adversely affect the clinical status of patients with current or prior symptoms of HFrEF are potentially harmful and should be avoided or withdrawn Table 11. 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. 