What is the initial approach for Guideline-Directed Medical Therapy (GDMT) in patients with heart failure?

Initial Approach for Guideline-Directed Medical Therapy (GDMT) in Heart Failure

The initial approach for Guideline-Directed Medical Therapy (GDMT) in heart failure with reduced ejection fraction (HFrEF) should be simultaneous initiation of all four core medication classes: ACE inhibitors/ARBs or preferably ARNI, beta-blockers, mineralocorticoid receptor antagonists (MRAs), and SGLT2 inhibitors. 1

Core Medication Classes and Initial Dosing

First-Line Medications

1. ARNI (Preferred) or ACE inhibitors/ARBs

   • Sacubitril/valsartan (ARNI): Start 24/26mg BID, target 97/103mg BID
   • Enalapril (ACEi alternative): Start 2.5mg BID, target 10-20mg BID
   • Valsartan (ARB alternative): For ACEi intolerance

2. Beta-blockers

   • Carvedilol: Start 3.125mg BID, target 25mg BID (<85kg) or 50mg BID (≥85kg)
   • Metoprolol succinate: Start 12.5-25mg daily, target 200mg daily
   • Bisoprolol: Start 1.25mg daily, target 10mg daily

3. Mineralocorticoid Receptor Antagonists (MRAs)

   • Spironolactone: Start 12.5-25mg daily, target 25-50mg daily
   • Eplerenone: Start 25mg daily, target 50mg daily

4. SGLT2 Inhibitors

   • Dapagliflozin: 10mg daily
   • Empagliflozin: 10mg daily

Implementation Strategy

The American College of Cardiology recommends starting all four medication classes simultaneously at diagnosis rather than sequential addition 1. This approach has been shown to significantly reduce mortality and morbidity compared to partial implementation of GDMT.

• In-hospital initiation: Starting medications during hospitalization improves adherence
• Heart failure clinic referral: Significantly increases GDMT implementation
• Nurse-led titration programs: Show higher rates of reaching target doses with associated reductions in mortality (RR: 0.66; 95% CI: 0.48-0.92)

Monitoring and Titration

1. Initial monitoring: Every 1-2 weeks after starting therapy

   • Vital signs (especially blood pressure)
   • Volume status
   • Renal function
   • Electrolytes (particularly potassium with MRAs)

2. Titration schedule:

   • Aim to achieve ≥80% of target doses for optimal outcomes 2
   • A GDMT score ≥5 (based on medication combinations and dosages) is associated with better outcomes even if all four drugs cannot be introduced 2

Additional Therapies to Consider

For patients who remain symptomatic despite core GDMT:

1. Ivabradine: For patients with:

   • Persistent heart rate ≥70 bpm
   • NYHA class II-IV symptoms
   • LVEF ≤35%
   • In sinus rhythm
   • On maximally tolerated beta-blocker therapy 3

2. Vericiguat: For higher-risk patients with:

   • Worsening HFrEF
   • LVEF <45%
   • Elevated natriuretic peptides
   • Recent HF hospitalization or IV diuretic use

3. Hydralazine-Isosorbide Dinitrate: Particularly beneficial for:

   • Black patients with HFrEF
   • Patients who cannot tolerate ACEi/ARB/ARNI due to renal dysfunction

Device Therapy Considerations

Consider device therapy after optimizing GDMT:

1. Implantable Cardioverter-Defibrillators (ICDs):

   • For primary prevention in patients with LVEF ≤35%
   • NYHA class II-III symptoms despite optimal GDMT
   • Patients receiving GDMT have lower 1-year mortality after ICD implantation

2. Cardiac Resynchronization Therapy (CRT):

   • For patients with LVEF ≤35%
   • QRS duration ≥150 ms
   • LBBB
   • NYHA class II-IV symptoms on GDMT

Common Pitfalls and How to Avoid Them

1. Underutilization of GDMT: Less than 1% of patients receive all life-prolonging treatments at trial-proven doses 1

   • Solution: Use heart failure clinics and nurse-led titration programs 4

2. Sequential rather than simultaneous initiation:

   • Solution: Start all four core medication classes at diagnosis 1

3. Inadequate dosing:

   • Solution: Aim for ≥80% of target doses; even if all four drugs cannot be introduced, a GDMT score ≥5 is associated with better outcomes 2

4. Failure to monitor appropriately:

   • Solution: Schedule multiple early post-discharge visits (in-person or virtual) 1

5. Discontinuation due to mild side effects:

   • Solution: Educate patients about expected side effects and their temporary nature

An intensive GDMT optimization program has been shown to be extremely cost-effective with incremental cost-effectiveness ratios <$10,000 per quality-adjusted life-year 5, making this approach not only clinically effective but also economically sound.