What are the newest guidelines for managing heart failure with reduced ejection fraction (HFrEF)?

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Last updated: October 6, 2025View editorial policy

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Newest Guidelines for Heart Failure with Reduced Ejection Fraction (HFrEF)

The current guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) now includes four medication classes: SGLT2 inhibitors, ARNi/ACEi/ARB, beta-blockers, and mineralocorticoid receptor antagonists (MRAs), all of which should be initiated and optimized to reduce mortality and hospitalizations. 1

Core Medication Classes for HFrEF

First-Line Therapies

  • SGLT2 inhibitors (empagliflozin 10mg daily or dapagliflozin 10mg daily) should be started early as they have minimal effect on blood pressure but provide rapid benefits in reducing heart failure hospitalizations and cardiovascular mortality 1, 2
  • Mineralocorticoid Receptor Antagonists (MRAs) (spironolactone 12.5-25mg daily or eplerenone 25mg daily) are indicated especially for patients with LVEF ≤35% and NYHA class II-IV symptoms 1, 3
  • Beta-blockers (carvedilol, metoprolol succinate, or bisoprolol) should be initiated at low doses and titrated to target doses to reduce mortality and hospitalizations 1
  • ARNi (sacubitril/valsartan) is recommended as a replacement for ACEi/ARB in patients who remain symptomatic despite optimal treatment with other therapies, starting with low dose (24/26mg-49/51mg twice daily) and titrating to 97/103mg twice daily 1

Implementation Strategy

  • Evaluate blood pressure, heart rate, volume status, and renal function before initiating therapy 2
  • For patients with adequate blood pressure, start SGLT2 inhibitor and MRA first, then add low-dose beta-blocker if heart rate >70 bpm, followed by ARNi 2
  • For patients with low blood pressure (SBP <100 mmHg), start with SGLT2 inhibitor and MRA as they have minimal BP-lowering effects 2
  • Diuretics should be used as needed for congestion but adjusted to avoid overdiuresis 1, 2

Special Populations and Considerations

Patients with Improved LVEF

  • Patients with previous HFrEF who improve their LVEF to >40% (termed HFimpEF) should continue their HFrEF treatment regimen 1

Additional Therapies for Specific Populations

  • Ivabradine (starting at 2.5-5mg twice daily) should be considered for patients in sinus rhythm with heart rate ≥70 bpm despite maximally tolerated beta-blocker therapy 1, 2
  • Hydralazine and isosorbide dinitrate combination provides additional benefit in self-identified African American patients with NYHA class III-IV symptoms despite optimal therapy 1
  • Intravenous iron replacement is recommended for patients with iron deficiency to improve functional status 4

Device Therapies

  • Implantable cardioverter-defibrillator (ICD) is recommended for primary prevention in patients with LVEF ≤35% despite ≥3 months of optimal medical therapy, with expected survival >1 year 1
  • Cardiac resynchronization therapy (CRT) is indicated for patients with LVEF ≤35%, sinus rhythm, left bundle branch block with QRS duration ≥150 ms, and NYHA class II-IV symptoms despite optimal therapy 1

Monitoring and Follow-up

  • Monitor serum potassium before initiating therapy, within the first week, and at one month after starting or adjusting MRA therapy 3
  • Assess renal function regularly, especially when using ACEi/ARB/ARNi and MRAs 1, 3
  • Adjust medication doses based on clinical response, with one drug at a time to identify the source of any adverse effects 2

Common Pitfalls to Avoid

  • Avoid sequential approach: Don't delay benefits of comprehensive therapy by adding one medication at a time over extended periods 2
  • Don't be overly cautious with dosing: Even lower-than-target doses provide significant benefits compared to no treatment 2
  • Avoid excessive diuresis: This can lead to hypotension and impair tolerance of other HF medications 2
  • Don't discontinue therapy when LVEF improves: Patients with improved LVEF should continue their HFrEF treatment 1
  • Avoid certain medications: Diltiazem, verapamil, and the combination of ACEi/ARB with MRA and ARB/renin inhibitor can worsen HF or cause adverse effects 1

Medication Target Doses

  • Beta-blockers: Bisoprolol 10mg once daily, Carvedilol 25-50mg twice daily, Metoprolol succinate 200mg daily 1
  • ARNi: Sacubitril/valsartan 97/103mg twice daily 1
  • MRAs: Eplerenone 50mg daily, Spironolactone 25-50mg daily 1
  • SGLT2 inhibitors: Dapagliflozin 10mg daily, Empagliflozin 10mg daily 1

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Initial Management Approach for Heart Failure with Reduced Ejection Fraction (HFrEF)

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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