What are the initial management and treatment options for patients with heart failure, particularly those with reduced ejection fraction?

Initial Management and Treatment of Heart Failure with Reduced Ejection Fraction

For patients with heart failure with reduced ejection fraction (HFrEF), the cornerstone of initial management should include four medication classes: SGLT2 inhibitors, mineralocorticoid receptor antagonists (MRAs), beta-blockers, and renin-angiotensin system inhibitors, with careful dose titration to maximize survival benefits. 1

Core Medication Classes for HFrEF

• SGLT2 inhibitors (dapagliflozin 10 mg daily or empagliflozin 10 mg daily) should be initiated early as they have minimal impact on blood pressure while providing significant mortality benefits 1

• Mineralocorticoid receptor antagonists (spironolactone 12.5-25 mg daily or eplerenone 25 mg daily) should be started concurrently with SGLT2 inhibitors in patients with eGFR >30 ml/min/1.73m² 1, 2

• Beta-blockers should be used in all patients with HFrEF to prevent symptomatic heart failure and reduce mortality 3

• ACE inhibitors or ARBs should be used in all patients with HFrEF to prevent symptomatic heart failure 3

• For patients who remain symptomatic despite ACE inhibitors and beta-blockers, angiotensin receptor-neprilysin inhibitors (ARNi) may be considered 3

Medication Initiation and Titration Strategy

• Start with low doses and titrate gradually to target doses shown to be effective in clinical trials 1

• Recommended sequence of initiation:

  1. SGLT2 inhibitor and MRA simultaneously
  2. Beta-blocker if heart rate >70 bpm
  3. ARNI or ACE inhibitor/ARB at low dose and titrate up 1

• For patients with atrial fibrillation, cardiac glycosides (digoxin) are indicated to slow ventricular rate and improve ventricular function and symptoms 3

• Ivabradine may be considered for patients with stable, symptomatic chronic heart failure with reduced ejection fraction to reduce the risk of hospitalization 4

Diuretic Therapy

• Loop diuretics should be administered for symptom relief in patients with fluid retention 1

• Diuretic dose should be adjusted based on volume status and reduced when initiating ACE inhibitors 3

• For patients with stage C heart failure and fluid retention, diuretics should be used in addition to ACE inhibitors and beta-blockers 3

• Initial diuretic treatment can include loop diuretics or thiazides, always administered in addition to an ACE inhibitor. If GFR < 30 ml/min, thiazides should not be used except as synergistic therapy with loop diuretics 3

Monitoring and Follow-up

• Monitor renal function and electrolytes 1-2 weeks after initiation and each dose increment of ACE inhibitors, ARBs, ARNIs, and MRAs 1

• When starting ACE inhibitors:

  1. Review the need for and dose of diuretics and vasodilators
  2. Avoid excessive diuresis before treatment
  3. Start with a low dose and build up to recommended maintenance dosages
  4. Check blood pressure, renal function, and electrolytes 1-2 weeks after each dose increment 3

Special Considerations

• In patients with eGFR <30 ml/min/1.73m², reduce or avoid MRAs and adjust RAS inhibitor dosing 1

• For patients with hyperkalemia (K+ >5.0 mEq/L), reduce MRA dose first 1

• Avoid non-steroidal anti-inflammatory drugs (NSAIDs) when initiating ACE inhibitor therapy 3

• In patients with diabetes and established heart failure with reduced ejection fraction, a sodium-glucose cotransporter 2 inhibitor with proven cardiovascular outcomes benefit is recommended 3

• Beta-blockers should be continued for 3 years after myocardial infarction 3

Common Pitfalls and Caveats

• Patients at highest risk of death are often least likely to receive appropriate medications like ACE inhibitors and beta-blockers 5

• Avoid excessive diuresis before starting ACE inhibitors, as this can lead to hypotension 3

• Contraindications for ivabradine include acute decompensated heart failure, clinically significant hypotension, sick sinus syndrome, sinoatrial block, 3rd-degree AV block, and severe hepatic impairment 4

• When using spironolactone, monitor for hyperkalemia, especially in patients with reduced renal function 2

• Metformin may be continued for glucose lowering in patients with type 2 diabetes with stable heart failure if estimated glomerular filtration rate remains >30 mL/min/1.73 m², but should be avoided in unstable or hospitalized patients with heart failure 3