What are the Guideline-Directed Medical Therapy (GDMT) guidelines for heart failure, specifically heart failure with reduced ejection fraction (HFrEF)?

Guideline-Directed Medical Therapy for Heart Failure with Reduced Ejection Fraction (HFrEF)

The cornerstone of HFrEF treatment is quadruple therapy consisting of an ARNI (or ACE inhibitor/ARB), beta-blocker, mineralocorticoid receptor antagonist (MRA), and SGLT2 inhibitor, all of which should be initiated early and titrated to target doses to reduce mortality and hospitalizations. 1

First-Line Medications for HFrEF

1. Renin-Angiotensin System Inhibitors

• First choice: Sacubitril/Valsartan (ARNI)

  • Preferred over ACE inhibitors as it demonstrated superior reduction in cardiovascular death and HF hospitalization (HR 0.80; 95% CI, 0.73-0.87) 2
  • Dosing:
    • Start: 49/51 mg twice daily
    • Target: 97/103 mg twice daily after 2-4 weeks 2
  • Contraindication: Requires 36-hour washout after ACE inhibitor 2

• Alternative: ACE inhibitors (if ARNI not available/tolerated)

  • Options: Enalapril 10-20 mg BID, Lisinopril 20 mg daily, or Ramipril 10 mg daily 1
  • Contraindicated with history of angioedema 1

• Alternative: ARBs (if ACE inhibitor not tolerated)

  • Options: Valsartan 160 mg BID, Candesartan 32 mg daily, or Losartan 150 mg daily 1
  • Note: ARBs have not consistently demonstrated mortality reduction unlike ACEIs 1

2. Beta-Blockers

• Evidence-based options:
  • Carvedilol: 3.125 mg BID → 25 mg BID (<85 kg) or 50 mg BID (≥85 kg)
  • Metoprolol succinate: 12.5-25 mg daily → 200 mg daily
  • Bisoprolol: 1.25 mg daily → 10 mg daily 1

3. Mineralocorticoid Receptor Antagonists (MRAs)

• For patients with LVEF ≤35% and persistent symptoms:
  • Spironolactone: 12.5-25 mg daily → 25-50 mg daily
  • Eplerenone: 25 mg daily → 50 mg daily 1
• Use with caution in renal dysfunction (eGFR <30 mL/min/1.73m²) 1

4. SGLT2 Inhibitors

• Recommended regardless of diabetic status:
  • Dapagliflozin: 10 mg daily
  • Empagliflozin: 10 mg daily 1
• Should be initiated early due to early clinical benefits 1

Initiation and Titration Strategy

1. Initial Approach:

   • Start ACE inhibitor/ARB/ARNI and beta-blocker simultaneously at diagnosis 1
   • Add diuretics for symptomatic relief if congestion is present 1
   • Add MRA for patients with LVEF ≤35% with persistent symptoms 1
   • Add SGLT2 inhibitor early in treatment course 1

2. Titration Protocol:

   • Increase doses every 2-4 weeks as tolerated 1, 2
   • Target maximum tolerated doses of each medication class 1
   • Monitor blood pressure, renal function, and electrolytes with each titration 1

3. For Hospitalized Patients:

   • Continue GDMT during hospitalization except in cases of hemodynamic instability 3
   • If beta-blocker therapy needs initiation, start at low dose after optimization of volume status 3
   • Provide thrombosis/thromboembolism prophylaxis 3
   • Schedule follow-up within 7-14 days and telephone follow-up within 3 days of discharge 3, 1

Monitoring and Follow-up

1. Regular Assessment:

   • Monitor symptoms, vital signs, volume status, and renal function 1
   • Measure serum electrolytes, urea nitrogen, and creatinine during medication titration 3
   • Consider natriuretic peptide monitoring 1
   • Re-evaluate LVEF periodically to guide treatment decisions 1

2. Post-Discharge Care:

   • Address initiation/optimization of GDMT at first post-discharge visit 3
   • Assess volume status and blood pressure with adjustment of therapy 3
   • Evaluate renal function and electrolytes 3
   • Reinforce HF education, self-care, and medication adherence 3

Device Therapy Considerations

1. Implantable Cardioverter-Defibrillator (ICD):

   • For primary prevention: Patients with LVEF ≤30-35% and NYHA class II-III symptoms despite optimal medical therapy 1
   • For secondary prevention: Patients with history of cardiac arrest or sustained ventricular tachycardia 1

2. Cardiac Resynchronization Therapy (CRT):

   • For patients with LVEF ≤35%, NYHA class II-IV symptoms despite optimal therapy, and QRS duration ≥130 msec 1

Common Pitfalls and Barriers to GDMT

1. Underutilization Issues:

   • Only 63.8% of eligible patients receive evidence-based beta-blockers 4
   • MRAs (17.6%) and SGLT2 inhibitors are particularly underutilized 4, 5
   • Target doses are rarely achieved (21.4% for beta-blockers, 45.8% for ACEIs/ARBs/ARNIs) 5

2. Common Barriers:

   • Renal dysfunction, hypotension, and hyperkalemia 6
   • Advanced age, higher EF, atrial fibrillation, COPD, prior stroke, and dementia 5
   • Lack of HF specialist involvement (HF clinic visits associated with 2.5× higher rate of evidence-based beta-blocker use) 4

3. Practical Solutions:

   • Consider early initiation of low-dose combination therapy for most patients 7
   • Prioritize removal of medications without clear cardiovascular benefit to reduce polypharmacy 7
   • Refer to HF specialists for optimization of therapy when possible 4

Remember that despite potential challenges with medication initiation and titration, the benefits of GDMT on morbidity and mortality are substantial, and every effort should be made to optimize therapy in all eligible patients with HFrEF.