What is the Guideline-Directed Medical Therapy (GDMT) for heart failure?

Guideline-Directed Medical Therapy for Heart Failure

The current guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) recommends simultaneous initiation of four core medication classes: ACE inhibitors/ARBs or preferably ARNI, beta-blockers, mineralocorticoid receptor antagonists (MRAs), and SGLT2 inhibitors to reduce morbidity and mortality. 1

Core Medication Classes for HFrEF

First-Line Agents and Dosing

1. ARNI (Preferred) or ACEi/ARB

   • Sacubitril/valsartan (ARNI): Start 24/26mg BID → Target 97/103mg BID
   • Enalapril (ACEi): Start 2.5mg BID → Target 10-20mg BID
   • Valsartan (ARB): 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

Additional Therapies for Specific Populations

1. Vericiguat

   • For higher-risk patients with worsening HFrEF, LVEF <45%, elevated natriuretic peptides, and recent HF hospitalization or IV diuretic use 1

2. Hydralazine-Isosorbide Dinitrate

   • Particularly beneficial for Black patients with HFrEF
   • For patients who cannot tolerate ACEi/ARB/ARNI due to renal dysfunction 1

3. 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 1, 2

Implementation Strategy

1. Initiation Approach

   • Start all four core medication classes simultaneously at diagnosis rather than sequentially 1
   • Begin with low doses and titrate gradually to target doses
   • In-hospital initiation for hospitalized patients improves adherence 1

2. Monitoring Requirements

   • Monitor vital signs, volume status, renal function, and electrolytes every 1-2 weeks initially 1
   • Pay particular attention to:
     • Hypotension (especially with ARNI/ACEi/ARB)
     • Hyperkalemia (especially with MRAs)
     • Worsening renal function
     • Fluid status 1

3. Dose Optimization

   • Target ≥80% of target doses for optimal outcomes
   • A GDMT score ≥5 (based on medication combinations and dosages) is associated with better outcomes even if all four drugs cannot be introduced 3

Device Therapy Considerations

1. Implantable Cardioverter-Defibrillators (ICDs)

   • Recommended for primary prevention in patients with LVEF ≤35% and NYHA class II-III symptoms despite optimal GDMT
   • Patients receiving GDMT have lower 1-year mortality after ICD implantation 1, 4

2. Cardiac Resynchronization Therapy (CRT)

   • Recommended for patients with LVEF ≤35%, QRS duration ≥150 ms, LBBB, and NYHA class II-IV symptoms on GDMT 1

Special Populations

1. Elderly Patients

   • No overall differences in safety or effectiveness have been observed between patients ≥65 years and younger adults 5
   • However, older patients with more comorbidities are less likely to receive GDMT 6

2. Renal Impairment

   • No dose adjustment required for mild to moderate renal impairment
   • For severe renal impairment (eGFR <30 mL/min/1.73m²), use half the starting dose for ARNI 5

3. Hepatic Impairment

   • No dose adjustment required for mild hepatic impairment
   • Use half the starting dose for moderate hepatic impairment (Child-Pugh B)
   • Not recommended for severe hepatic impairment (Child-Pugh C) 5

Implementation Challenges and Solutions

1. Barriers to GDMT Implementation

   • Less than 1% of patients receive all life-prolonging treatments at trial-proven doses 1
   • Older patients and those with comorbidities (COPD, atrial fibrillation, stroke, dementia) are less likely to receive GDMT 6

2. Solutions

   • Heart failure clinic referral significantly increases GDMT implementation 1, 7
   • Nurse-led titration programs show higher rates of reaching target doses with associated reductions in mortality 1
   • Schedule multiple early post-discharge visits (in-person or virtual) 1

Clinical Outcomes

Implementation of comprehensive GDMT significantly reduces all-cause mortality, cardiovascular mortality, heart failure hospitalizations, and improves quality of life. A multimodal combination strategy with all four medication classes provides the greatest mortality benefit compared to partial implementation of GDMT 1.