What is the initial approach to Guideline-Directed Medical Therapy (GDMT) for patients with Heart Failure with preserved Ejection Fraction (HFpEF)?

Initial Approach to Guideline-Directed Medical Therapy for HFpEF

The initial approach to GDMT for HFpEF should focus on SGLT2 inhibitors as first-line therapy, followed by judicious use of diuretics for symptom management, and consideration of MRAs, ARNIs, or ARBs based on specific patient characteristics. 1

Core Components of HFpEF Management

The management of HFpEF focuses on three key strategies:

1. Risk stratification and comorbidity management including:

   • Hypertension
   • Diabetes mellitus
   • Obesity
   • Atrial fibrillation
   • Coronary artery disease
   • Chronic kidney disease
   • Obstructive sleep apnea 1

2. Nonpharmacological management including:

   • Exercise and weight loss
   • Consideration of wireless pulmonary artery monitoring in selected cases 1

3. Pharmacological therapy for symptom management and disease modification 1

First-Line Pharmacological Therapy

SGLT2 Inhibitors

• First choice for most patients with HFpEF based on strong evidence from recent trials
• Both dapagliflozin (DELIVER trial) and empagliflozin (EMPEROR-PRESERVED trial) demonstrated significant reductions in:
  • Worsening HF events
  • HF hospitalizations (HR: 0.77 and 0.71, respectively)
  • Composite of worsening HF and cardiovascular death 1
• Key advantage: Rarely cause hypotension, making them ideal first-line agents 1

Diuretics

• Should be used judiciously for symptom management and volume control
• Target relief of congestion while avoiding overdiuresis 1
• Loop diuretics are the mainstay for acute volume management 2

Second-Line Pharmacological Options

Mineralocorticoid Receptor Antagonists (MRAs)

• Consider in appropriate patients based on TOPCAT trial data
• Spironolactone showed benefit in reducing HF hospitalizations (HR: 0.83) 1
• Caution: Monitor for hyperkalemia and renal dysfunction 1

Angiotensin Receptor-Neprilysin Inhibitors (ARNIs)

• Consider in selected patients, particularly:
  • Those with lower ejection fraction (closer to 40-45%)
  • Women (showed greater benefit in PARAGON-HF) 1
• Sacubitril/valsartan showed trend toward benefit in PARAGON-HF trial 1
• Caution: More likely to cause symptomatic hypotension than other agents 1

Angiotensin Receptor Blockers (ARBs)

• Consider in selected patients
• Candesartan showed modest benefit in CHARM-PRESERVED trial 1

Sequencing and Titration Approach

1. Start with SGLT2 inhibitor as first-line therapy 1, 3
2. Add/adjust diuretics based on congestion status 1, 2
3. Consider adding MRA if appropriate (monitor potassium and renal function) 1
4. Consider ARNI or ARB based on individual characteristics and tolerability 1

Special Considerations

Beta-Blockers

• Not recommended as primary HFpEF therapy unless specific indications exist:
  • Recent myocardial infarction (within 3 years)
  • Angina
  • Atrial fibrillation requiring rate control 1
• Monitor for chronotropic incompetence which can worsen exercise intolerance 1

Phenotype-Guided Approach

• Consider tailoring therapy based on predominant phenotypes:
  • Obesity/metabolic syndrome
  • Hypertensive
  • Atrial fibrillation
  • Pulmonary hypertension 4, 3

Common Pitfalls to Avoid

• Treating HFpEF like HFrEF: Several therapies beneficial in HFrEF have shown no benefit in HFpEF (perindopril, irbesartan, digoxin, nitrates, ivabradine, sildenafil) 1, 2
• Overlooking specific etiologies: Always consider specific causes of HFpEF that may require targeted therapy (amyloidosis, hemochromatosis, hypertrophic cardiomyopathy) 1, 3
• Excessive diuresis: Can lead to hypotension and worsened symptoms 2
• Failure to address comorbidities: Management of associated conditions is essential for optimal outcomes 1, 4

Monitoring and Follow-up

• Assess volume status regularly
• Monitor renal function and electrolytes, especially with MRAs
• Evaluate symptoms and functional capacity
• Consider natriuretic peptide levels to assess disease severity 1
• Adjust therapy based on clinical response and tolerability 1