What are examples of Guideline-Directed Medical Therapy (GDMT)?

Examples of Guideline-Directed Medical Therapy (GDMT)

Guideline-Directed Medical Therapy (GDMT) for heart failure includes four cornerstone drug classes: renin-angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and SGLT2 inhibitors, which together can reduce mortality risk by up to 73% over 2 years in patients with heart failure with reduced ejection fraction (HFrEF). 1

Core GDMT Medications for HFrEF

1. Renin-Angiotensin System (RAS) Inhibitors

• Angiotensin-Converting Enzyme (ACE) Inhibitors
  • Enalapril (starting: 2.5mg BID; target: 10-20mg BID)
  • Lisinopril, ramipril, captopril
• Angiotensin Receptor Blockers (ARBs)
  • Valsartan, candesartan, losartan
• Angiotensin Receptor-Neprilysin Inhibitors (ARNIs)
  • Sacubitril/valsartan (starting: 24/26mg BID; target: 97/103mg BID) - preferred over ACE inhibitors/ARBs when possible 1

2. Beta-Blockers

• Evidence-based beta-blockers for HF
  • Carvedilol (starting: 3.125mg BID; target: 25mg BID for <85kg or 50mg BID for ≥85kg)
  • Metoprolol succinate (starting: 12.5-25mg daily; target: 200mg daily)
  • Bisoprolol (starting: 1.25mg daily; target: 10mg daily) 1

3. Mineralocorticoid Receptor Antagonists (MRAs)

• Spironolactone (starting: 12.5-25mg daily; target: 25-50mg daily)
• Eplerenone (starting: 25mg daily; target: 50mg daily) 1

4. Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors

• Dapagliflozin (10mg daily)
• Empagliflozin (10mg daily) 1

Additional Medications for Specific Indications

5. Diuretics

• Loop diuretics (furosemide, torsemide, bumetanide)
• Used primarily for symptom management and congestion relief 2

6. Vasodilators (Particularly for Black Patients)

• Hydralazine and isosorbide dinitrate combination 3

7. Other Medications for Specific Indications

• Ivabradine (for patients with persistent heart rate ≥70 bpm despite beta-blocker therapy)
• Digoxin (for symptom management in selected patients) 3

GDMT for HFpEF (Heart Failure with Preserved Ejection Fraction)

Recent clinical trials have demonstrated benefits of certain GDMT medications in HFpEF:

• SGLT2 inhibitors (dapagliflozin, empagliflozin)
• MRAs (spironolactone)
• ARNIs (sacubitril/valsartan) 2

Implementation Considerations

Optimal Sequencing

The American College of Cardiology recommends:

1. Start with beta-blockers
2. Add RAS inhibitors (preferably ARNI)
3. Add MRAs
4. Add SGLT2 inhibitors 1

Dosing Strategy

• Target doses should be achieved whenever possible
• Even suboptimal doses provide benefit compared to no therapy
• A GDMT score ≥5 (based on medication combinations and dosages) is associated with improved outcomes even if all four drug classes cannot be used 4

Common Pitfalls to Avoid

1. Delaying quadruple therapy initiation - all four drug classes should be initiated as soon as possible
2. Inadequate dose titration - forced-titration strategies should be used to achieve maximum benefits
3. Waiting for clinical deterioration - therapies should be added even if patients appear clinically stable
4. Inappropriate medication discontinuation - many adverse events attributed to GDMT may actually be manifestations of heart failure itself 2, 1

Gaps in GDMT Implementation

Despite strong evidence, significant gaps exist in GDMT utilization:

• Only about 25% of eligible patients receive all recommended medications
• Only 1% receive target doses of all medications 2
• Older patients and those with comorbidities are less likely to receive appropriate GDMT 5
• Cardiologists are more likely to prescribe and adjust GDMT than general medicine physicians 3

Implementing GDMT requires a systematic approach with regular monitoring of symptoms, vital signs, volume status, and renal function to ensure optimal therapy and minimize adverse effects.