Table 5.

Therapies for Heart Failure with Reduced Ejection Fraction1

Drug ClassInitial DoseTarget or Maximum DoseComments
ARNi

  1. Avoid if hemodynamically unstable, history of angioedema, or potassium level ≥ 5 mmol/L

  2. Preferred over ACE-I and ARB due to superior efficacy

Sacubutril-valsartan24/26 mg twice daily if ACE inhibitor or ARB naïve or 49/51 mg twice daily with adequate blood pressure (SBP ≥ 120 mmHg)97/103 mg twice dailyOriginal study excluded patients with SBP < 100 mmHg
ACE Inhibitor

  1. Similar restrictions to ARNi

  2. Use if ARNi is not feasible

Captopril6.25 mg 3 times daily50 mg 3 times daily
Enalaprol2.5 mg twice daily10–20 mg twice daily
Lisinopril5 mg daily20–40 mg daily
Ramipril1.25–2.5 mg daily10 mg daily
ARB

  1. Class preferred with history of angioedema or intolerance to ARNi and ACEi

  2. Use if ARNi is not feasible

Candesartan4–8 mg daily32 mg daily
Losartan25–50 mg daily50–150 mg daily
Valsartan20–40 mg twice daily160 mg twice daily
Beta Blocker

  1. Class-wide risk of hypotension, worsening asthma, and contraindicated in untreated high-degree heart block

  2. Limit to carvedilol, metoprolol succinate, and bisprolol; It is not class-wide benefit.

Carvedilol3.125 mg twice daily25–50 mg twice daily6.25 mg is the minimal effective dose. Benefits increases with increasing dose to 25 mg.
Metoprolol succinate extended release12.5–25 mg daily200 mg daily
Bisoprolol1.25 mg daily10 mg daily
SGLT2iRisk of euglycemic ketoacidosis and urinary tract infections
Dapagliflozin10 mg daily
Empagliflozin10 mg or 25 mg daily25 mg if patient also has type-2 diabetes.
MRADose-adjustment or contraindicated depending on renal and potassium status; do not use if potassium level ≥ 5 mmol/L or Cr ≥ 2.5 mg/dL. Avoid if eGFR < 30 mL/min.
Spironolactone12.5–25 mg daily25–50 mg dailyRisk of gynecomastia, breast pain, menstrual irregularities, decreased libido
Eplerenone25 mg daily50 mg dailyLower risk of gynecomastia
Additional TherapiesComments
Hydralazine plus nitrateComments
Fixed-dose combination20 mg isosorbide dinitrate/37.5 mg hydralazine three times a day40 mg/75 mg 3 times a day

  1. If patient is intolerant of RAAS inhibition

  2. African American patients on maximum GDMT needing additional benefit

Separate isosorbide dinitrate and hydralazine20 mg isosorbide dinitrate and 25 mg hydralazine both three times a day40/75 three times a day
Cardiac glycosideComments
Digoxin0.125–0.25 mg dailyNo target doseCare with decreased creatinine clearance
Selective sinus node inhibitor
Ivabradine2.5–5 mg twice daily7.5 mg twice dailyUsed if HR ≥ 70 in setting of maximal GDMT
Soluble guanylate cyclase inhibitor
Vericiguat2.5 mg daily10 mg daily

  1. Use for patients who cannot tolerate or is already on all 4 major categories of beta-blocker, ARNi, Anti-aldosterone, and SGLT2i.

  2. Can cause hypotension, this is a major limitation

Implanted DevicesDeviceClass-1 Indication per AHA/ACC/HFSABenefitComments
Automated implanted defibrillator (AICD)LVEF≤ 30%, NYHA class-1, > 40 days post MI, expected to live > 1 yearOnly prevents sudden cardiac death (SCD)thereby reducing mortalityDoes not improve cardiac function
Automated implanted defibrillator (AICD)LVEF≤ 35%, NYHA class 2–3, expected to live > 1 yearOnly prevents SCD thereby reducing mortalityDoes not improve cardiac function
Cardiac resynchronization therapy (CRT) with defibrillatorLVEF≤ 35%, NYHA class 2–3, or on chronic IV infusion, expected to live > 1 year, left bundle branch block on ECG with QRS duration ≥ 150 msImproves quality of life, reduce hospital re-admission, prevents SCD, reduce mortality

  1. Can improve cardiac function in ∼ 2/3 of cases

  2. Can provide benefit with CRT-P (i.e., without defibrillation option)

  • ↵12. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol May 3 2022;79(17):e263-e421. doi:10.1016/j.jacc.2021.12.012.