What is the current guideline-directed medical therapy for heart failure with preserved ejection fraction (HFpEF)?

Current Guideline-Directed Medical Therapy for Heart Failure with Preserved Ejection Fraction (HFpEF)

SGLT2 inhibitors are the first-line disease-modifying therapy for patients with HFpEF, with a Class 2a recommendation (Level of Evidence: B-R) due to their significant reductions in heart failure hospitalizations and cardiovascular mortality. 1, 2

First-Line Pharmacological Therapy

• SGLT2 inhibitors (dapagliflozin, empagliflozin) have demonstrated significant reductions in heart failure hospitalizations and composite cardiovascular outcomes in patients with HFpEF, as evidenced by the DELIVER and EMPEROR-PRESERVED trials 2
• The American College of Cardiology/American Heart Association/Heart Failure Society of America guidelines give SGLT2 inhibitors a Class 2a recommendation (Level of Evidence: B-R), indicating they "can be beneficial in decreasing HF hospitalizations and cardiovascular mortality" 1
• SGLT2 inhibitors should be initiated early in the treatment course to maximize mortality and morbidity benefits 2

Symptom Management

• Loop diuretics should be used at the lowest effective dose to manage fluid retention and relieve congestion, with titration based on symptoms and volume status 2
• Consider increasing loop diuretic dose before adding a thiazide diuretic if the initial diuretic response is inadequate 2
• Diuretics remain the mainstay for symptom management but do not modify disease progression 3

Additional Pharmacological Options

• Mineralocorticoid receptor antagonists (MRAs) like spironolactone have a Class 2b recommendation (Level of Evidence: B-R), indicating they "may be considered to decrease hospitalizations, particularly among patients with LVEF on the lower end of this spectrum" (closer to 45-50%) 1, 2
• Angiotensin receptor-neprilysin inhibitors (ARNi) such as sacubitril/valsartan also have a Class 2b recommendation (Level of Evidence: B-R) and may be considered for selected patients, especially those with LVEF on the lower end of the preserved spectrum 1
• Angiotensin receptor blockers (ARBs) have a Class 2b recommendation (Level of Evidence: B-R) and may be considered to decrease hospitalizations, particularly in patients with LVEF closer to 50% 1

Management of Comorbidities

• Hypertension management is critical with a Class 1 recommendation (Level of Evidence: C-LD) - medications should be titrated to attain blood pressure targets in accordance with published clinical practice guidelines 1
• Management of atrial fibrillation can be useful to improve symptoms (Class 2a recommendation, Level of Evidence: C-EO) 1
• For patients with both HFpEF and atrial fibrillation, anticoagulation should be prescribed based on CHA₂DS₂-VASc score to prevent thromboembolic events 4

Treatments to Avoid

• Routine use of nitrates or phosphodiesterase-5 inhibitors to increase activity or quality of life is ineffective and has a Class 3: No Benefit recommendation (Level of Evidence: B-R) 1
• Patients with HFpEF should not be treated with the same approach as those with heart failure with reduced ejection fraction (HFrEF), as response to therapies differs significantly between these populations 2

Treatment Algorithm for HFpEF

1. First-line therapy: SGLT2 inhibitor (Class 2a) 1, 2
2. Symptom management: Diuretics as needed for congestion 1, 2
3. Consider adding (especially for LVEF closer to 50%):
   • MRA (spironolactone) (Class 2b) 1, 2
   • ARNi (sacubitril/valsartan) (Class 2b) 1
   • ARB (Class 2b) 1
4. Optimize comorbidities:
   • Treat hypertension (Class 1) 1
   • Manage atrial fibrillation (Class 2a) 1

Special Considerations

• Patients who improve their LVEF from reduced (<40%) to preserved (≥50%) are classified as having HF with improved EF (HFimpEF) and should continue their HFrEF treatment (Class 1 recommendation, Level of Evidence: B-R) 1
• Regular monitoring of volume status, renal function, and electrolytes is essential, especially with MRA therapy 2
• When prescribing spironolactone, careful monitoring of potassium and renal function is necessary to minimize the risk of hyperkalemia 2

Emerging Approaches

• Phenotype-guided approaches are being developed to better tailor therapy to individual patient characteristics and comorbidity profiles 5, 6
• Non-pharmacological interventions including supervised exercise training programs can improve functional capacity and quality of life 2
• Multidisciplinary heart failure programs should be offered to all patients 2