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

Guideline-Directed Medical Therapy (GDMT) for Heart Failure

The American College of Cardiology recommends simultaneous initiation of four core medication classes for patients with heart failure with reduced ejection fraction (HFrEF): 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

1. Renin-Angiotensin System Inhibitors

• First choice: Sacubitril/valsartan (ARNI)
  • Starting dose: 24/26mg BID
  • Target dose: 97/103mg BID 1, 2
• Alternatives if ARNI not tolerated:
  • ACE inhibitors (e.g., Enalapril: 2.5mg BID → 10-20mg BID)
  • ARBs (e.g., Valsartan) for patients with ACE inhibitor intolerance 1

2. Beta-Blockers

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

3. Mineralocorticoid Receptor Antagonists (MRAs)

• Spironolactone: 12.5-25mg daily → 25-50mg daily
• Eplerenone: 25mg daily → 50mg daily 1

4. SGLT2 Inhibitors

• Dapagliflozin: 10mg daily
• Empagliflozin: 10mg daily
• Note: Beneficial regardless of diabetic status (Class 1 recommendation) 1

Additional Therapies for Specific Populations

For Higher-Risk Patients with Worsening HFrEF

• Vericiguat for patients with LVEF <45%, elevated natriuretic peptides, and recent HF hospitalization or IV diuretic use 1

For Black Patients or Those Unable to Tolerate ACEi/ARB/ARNI

• Hydralazine-Isosorbide Dinitrate particularly beneficial for Black patients with HFrEF and for patients who cannot tolerate ACEi/ARB/ARNI due to renal dysfunction 1

For Patients with Persistent Heart Rate ≥70 bpm

• Ivabradine for patients with:
  • NYHA class II-IV symptoms
  • LVEF ≤35%
  • In sinus rhythm
  • On maximally tolerated beta-blocker therapy 1, 3

Implementation Strategy

1. Start all four core medication classes simultaneously at diagnosis rather than sequential addition 1
2. Begin with low doses and titrate gradually to target doses
3. Aim for ≥80% of target doses for optimal outcomes 1, 4
4. Consider heart failure clinic referral which significantly increases GDMT implementation 1, 5
5. For hospitalized patients, initiate GDMT before discharge to improve adherence 1

Monitoring and Titration

• Initial monitoring: Every 1-2 weeks for vital signs, volume status, renal function, and electrolytes 1
• Laboratory assessments: Monitor renal function and electrolytes (particularly potassium) before initiation and 1-2 weeks after starting or titrating MRAs 1
• Schedule multiple early post-discharge visits (in-person or virtual) 1

Device Therapy Considerations

• Implantable Cardioverter-Defibrillators (ICDs) for primary prevention in patients with:
  • LVEF ≤35%
  • NYHA class II-III symptoms despite optimal GDMT 1, 6
• Cardiac Resynchronization Therapy (CRT) for patients with:
  • LVEF ≤35%
  • QRS duration ≥150 ms
  • LBBB
  • NYHA class II-IV symptoms on GDMT 1

Common Pitfalls and Challenges

1. Underutilization of GDMT: Less than 1% of patients receive all life-prolonging treatments at trial-proven doses 1, 7
2. Inadequate dosing: Only 21.4% of patients on beta-blockers and 45.8% on ACEi/ARB/ARNI achieve ≥80% of target doses 7
3. Failure to use all four medication classes: Even if all four drugs cannot be introduced, aim for a GDMT score ≥5 for better outcomes 1, 4
4. Barriers to implementation: Age, comorbidities (particularly renal dysfunction, COPD), and lack of heart failure clinic referral 5, 7

Clinical Outcomes

Implementation of comprehensive GDMT significantly reduces:

• All-cause mortality
• Cardiovascular mortality
• Heart failure hospitalizations
• Improves quality of life 1

Patients receiving GDMT before ICD implantation have significantly lower 1-year mortality (11.1% vs 16.2%) compared to those without GDMT 6.