What is the management of Heart Failure with Reduced Ejection Fraction (HFrEF)?

From the Guidelines

Management of heart failure with reduced ejection fraction (HFrEF) should prioritize guideline-directed medical therapy, including four medication classes: ACE inhibitors/ARNIs, beta-blockers, mineralocorticoid receptor antagonists (MRAs), and SGLT2 inhibitors, as recommended by the 2022 AHA/ACC/HFSA guideline 1. The cornerstone of treatment includes:

• ACE inhibitors or ARNIs, such as lisinopril (10-40 mg daily) or sacubitril/valsartan (24/26 mg to 97/103 mg twice daily)
• Beta-blockers, such as carvedilol (3.125-25 mg twice daily), metoprolol succinate (12.5-200 mg daily), or bisoprolol (1.25-10 mg daily)
• MRAs, such as spironolactone (25-50 mg daily) or eplerenone (25-50 mg daily)
• SGLT2 inhibitors, such as dapagliflozin (10 mg daily) or empagliflozin (10 mg daily), regardless of diabetes status These medications work synergistically to reduce mortality and hospitalizations by addressing neurohormonal activation, reducing cardiac remodeling, and improving cardiac efficiency, as supported by the European Journal of Heart Failure study 1. Regular monitoring of renal function, electrolytes, and blood pressure is essential, with medication doses titrated to target doses as tolerated, in line with the European Heart Journal guidelines 1. For patients who remain symptomatic despite optimal medical therapy, device therapies like implantable cardioverter-defibrillators or cardiac resynchronization therapy should be considered based on ejection fraction, QRS duration, and symptoms. Key considerations in the management of HFrEF include:
• Diuretics, such as furosemide, for volume management
• Regular assessment of patient symptoms and adjustment of medication doses as needed
• Referral to a heart failure specialty team for patients with advanced HF who wish to prolong survival, as recommended by the 2022 AHA/ACC/HFSA guideline 1.

From the FDA Drug Label

Sacubitril and valsartan tablets are indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure and reduced ejection fraction. Spironolactone tablets are indicated for treatment of NYHA Class III-IV heart failure and reduced ejection fraction to increase survival, manage edema, and reduce the need for hospitalization for heart failure.

The management of Heart Failure with Reduced Ejection Fraction (HFrEF) involves the use of medications such as sacubitril and valsartan tablets and spironolactone tablets.

• Sacubitril and valsartan tablets are indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure and reduced ejection fraction 2.
• Spironolactone tablets are indicated for treatment of NYHA Class III-IV heart failure and reduced ejection fraction to increase survival, manage edema, and reduce the need for hospitalization for heart failure 3.

From the Research

Management of Heart Failure with Reduced Ejection Fraction (HFrEF)

• HFrEF is a complex and progressive clinical condition characterized by dyspnea and functional impairment, with a high burden of mortality and readmission rate 4.
• Basic treatment strategies for HFrEF include diuretics for symptom relief and quadruple therapy (Angiotensin receptor blocker/neprilysin inhibitors, evidence-based beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose co-transporter 2 inhibitors) for reduction in hospitalizations, all-cause mortality, and cardiovascular mortality 4, 5, 6.
• Other medications such as intravenous iron, ivabradine, hydralazine/nitrates, and vericiguat may also have a role in certain subgroups of HFrEF patients 4, 6.
• Specific groups of patients with HFrEF may be candidates for device therapies such as implanted cardioverter defibrillators, cardiac resynchronization therapy, and trans catheter mitral valve repair 4.

Treatment Options

• The European Society of Cardiology (ESC), Canadian Cardiovascular Society, and the American College of Cardiology Heart Failure (HF) guidelines recommend the use of Angiotensin Converting Enzyme (ACE) inhibitors or Angiotensin Receptor Blockers (ARBs) and Beta Blockers (BB) in the treatment of HF with a reduced ejection fraction (HFrEF) 5.
• Newer medications targeting combining an ARB with a neprilysin inhibitor (ARNI) sacubitril/valsartan have shown benefits in mortality and can be used in place of an ACE inhibitor or an ARB 5, 7.
• Dapagliflozin, a medication targeting the sodium-glucose cotransporter 2 (SGLT2), can be used in addition to current therapies 5, 6.

Initiation and Optimization of Therapy

• The initiation or optimization of the four pillars of HFrEF therapy (beta-blockers, mineralocorticoid receptor antagonists, angiotensin receptor-neprilysin inhibitors, and sodium-glucose cotransporter-2 inhibitors) during hospitalization for acute decompensation is feasible and well-tolerated 8.
• Early intervention leads to improvements in clinical parameters and functional status, supporting guideline recommendations for in-hospital initiation or optimization of HFrEF therapy 8.
• Special consideration should be given to renal function when optimizing therapy 8.