What are the recommended drugs for Heart Failure with Preserved Ejection Fraction (HFpEF)?

Recommended Drugs for Heart Failure with Preserved Ejection Fraction (HFpEF)

SGLT2 inhibitors (empagliflozin or dapagliflozin) are the first-line disease-modifying therapy for HFpEF, followed by diuretics for symptom management, with MRAs, ARNi, and ARBs as additional options for selected patients. 1

First-Line Therapies

SGLT2 Inhibitors

• Class of recommendation: 2a (ACC/AHA) 1
• Empagliflozin and dapagliflozin have shown significant benefits in HFpEF:
  • 21% reduction in composite endpoint of HF hospitalization or CV death
  • 29% reduction in HF hospitalizations
  • Improved quality of life and slowed eGFR decline 1
• Benefits are independent of diabetes status
• Recommended for all symptomatic HFpEF patients with LVEF >40% and elevated natriuretic peptides 1

Diuretics

• Class of recommendation: I (ACC/AHA) 1
• Essential for symptom relief in volume-overloaded patients
• Loop diuretics preferred, especially in patients with CKD stage 3b or worse
• Goal: Achieve euvolemia with lowest effective dose
• Require monitoring of renal function and electrolytes 2

Second-Line Therapies

Mineralocorticoid Receptor Antagonists (MRAs)

• Class of recommendation: 2b (ACC/AHA) 1
• Consider in patients with:
  • LVEF ≥45%
  • Elevated natriuretic peptides or HF hospitalization within 1 year
  • No contraindications to MRAs 1
• Most beneficial in patients with LVEF closer to 50% 1
• Requires monitoring of potassium and renal function

Angiotensin Receptor-Neprilysin Inhibitors (ARNi)

• Class of recommendation: 2b (ACC/AHA) 1
• Sacubitril/valsartan may be considered in selected patients
• More beneficial in:
  • Women
  • Patients with LVEF ≤57%
  • Patients with LVEF closer to 50% 2

Angiotensin Receptor Blockers (ARBs)

• Class of recommendation: 2b (ACC/AHA) 1
• Candesartan showed borderline benefit in CHARM-Preserved trial (HR: 0.86) 2
• Consider for patients with hypertension and HFpEF
• Most beneficial in patients with LVEF closer to 50% 1

Management Algorithm for HFpEF

1. Start with SGLT2 inhibitor (empagliflozin or dapagliflozin)

   • For all symptomatic HFpEF patients regardless of diabetes status

2. Add diuretics for volume overload

   • Titrate to achieve euvolemia
   • Monitor renal function and electrolytes

3. Consider adding MRA if:

   • LVEF 45-60%
   • Elevated natriuretic peptides or recent HF hospitalization
   • No contraindications (monitor K+ and renal function)

4. Consider ARNi or ARB if:

   • LVEF closer to 50%
   • Persistent symptoms despite above therapies
   • ARNi preferred for women and those with LVEF ≤57%

5. Manage comorbidities aggressively

   • Hypertension: Target SBP <130 mmHg 2
   • Atrial fibrillation: Rate or rhythm control as appropriate 1
   • Diabetes: Optimize glycemic control
   • Obesity: Weight reduction for BMI ≥30
   • Sleep apnea: Screening and appropriate treatment

Important Considerations

• Beta-blockers: Not recommended specifically for HFpEF treatment but may be used for comorbidities:

  • Prior myocardial infarction (for up to 3 years)
  • Symptomatic coronary artery disease
  • Atrial fibrillation with rapid ventricular response 1, 3
  • Monitor for chronotropic incompetence which may worsen exercise intolerance

• Treatments to avoid:

  • Routine use of nitrates or phosphodiesterase-5 inhibitors (Class III: No Benefit) 1
  • Combining verapamil or diltiazem with beta-blockers in AF 1
  • Combining ARB with ACE inhibitors and beta-blockers 1

• Monitoring requirements:

  • Symptoms and volume status
  • Renal function and electrolytes (especially with RAAS inhibitors)
  • Repeat echocardiography with significant clinical changes 2

By following this evidence-based approach to HFpEF management, focusing on SGLT2 inhibitors as first-line therapy and appropriate use of diuretics, MRAs, ARNi, and ARBs, clinicians can effectively reduce hospitalizations and improve quality of life for patients with this challenging condition.