What is the treatment for a patient with reduced ejection fraction?

Treatment for Heart Failure with Reduced Ejection Fraction

The contemporary core treatment for patients with heart failure with reduced ejection fraction (HFrEF) includes four main drug classes: angiotensin receptor-neprilysin inhibitors (ARNI) or angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB), beta-blockers (BB), mineralocorticoid receptor antagonists (MRA), and sodium-glucose cotransporter 2 inhibitors (SGLT2i), along with diuretics for congestion management. 1

Core Medication Classes

First-Line Therapies

• ARNI (sacubitril/valsartan) is preferred over ACEI/ARB due to greater mortality benefit (at least 20% reduction in risk of death compared to 5-16% with ACEI/ARB alone) 1
• Beta-blockers with proven mortality benefit (carvedilol, metoprolol succinate, or bisoprolol) reduce risk of death by at least 20% and specifically reduce sudden death risk 1
• MRAs (spironolactone, eplerenone) reduce mortality by 30% in NYHA class III-IV HF with EF ≤35% 2
• SGLT2 inhibitors should be initiated in all patients with HFrEF with eGFR >20 ml/min/1.73m² 1

Diuretics

• Loop diuretics should be used for congestion management but titrated to avoid overdiuresis which can lead to hypotension 1

Optimization Strategy

Initiation and Titration

• Start with low doses and titrate gradually to target doses or highest tolerated doses 1
• Up-titrate one drug at a time using small increments until target or highest tolerated dose is achieved 1
• For patients with low blood pressure (BP), consider starting with medications having less impact on BP:
  • SGLT2 inhibitors and MRAs have minimal BP-lowering effects and can be initiated first 1
  • Follow with beta-blockers (if heart rate >70 bpm) or low-dose ARNI/ACEI/ARB 1

Blood Pressure Considerations

• For patients with symptomatic low BP:
  • Space out medications to reduce synergistic hypotensive effects 1
  • Consider selective β₁ receptor blockers (metoprolol, bisoprolol) which have less BP-lowering effect than non-selective beta-blockers 1
  • If beta-blockers aren't tolerated, consider ivabradine for patients in sinus rhythm 1

Heart Rate Management

• If target heart rate (<70 bpm) isn't achieved with beta-blockers:
  • Add ivabradine for patients in sinus rhythm 1
  • Consider digoxin for patients with atrial fibrillation 1

Special Considerations

Renal Function

• For patients with eGFR <30ml/min:
  • Reduce doses of renin-angiotensin system inhibitors 1
  • SGLT2i can still be used if eGFR >20 ml/min/1.73m² 1

Electrolyte Management

• For patients with elevated potassium (>5.0mEq/L):
  • Consider reducing MRA dose first, then beta-blockers 1
  • Monitor serum electrolytes regularly, especially during dose adjustments 1

Multidisciplinary Approach

• Implement standardized multidisciplinary team management from primary to tertiary care levels 1
• Provide patient education about condition, treatment plan, and lifestyle modifications 1
• Ensure seamless transition of care between different healthcare levels 1

Common Pitfalls and Caveats

• Clinical inertia: Many patients remain on suboptimal doses indefinitely. Follow forced-titration strategies used in clinical trials to achieve target doses unless patients experience intolerable adverse effects 1
• Hypotension concerns: Asymptomatic low BP should not prevent GDMT optimization; focus on symptomatic hypotension 1
• Discontinuation during hospitalization: Continue GDMT during hospitalization for HF exacerbation unless hemodynamic instability is present 1
• Underutilization: Less than 1% of patients receive all life-prolonging treatments at trial-proven doses despite clear mortality benefits 1
• Inadequate follow-up: Close monitoring is essential during initiation and titration phases to manage side effects and ensure optimal dosing 1