What medications are recommended for Heart Failure with preserved Ejection Fraction (HFpEF)?

Medications for Heart Failure with Preserved Ejection Fraction (HFpEF)

SGLT2 inhibitors are the first-line pharmacological therapy for patients with HFpEF, as they have demonstrated significant reduction in heart failure hospitalizations and cardiovascular mortality. 1

First-Line Medications

• SGLT2 inhibitors (empagliflozin, dapagliflozin): These medications have shown a 21% reduction in the composite endpoint of heart failure hospitalization and cardiovascular death in patients with HFpEF, primarily driven by reduction in hospitalizations 1
• Diuretics: Loop diuretics should be used judiciously in patients with signs and symptoms of congestion to improve symptoms and exercise capacity 1

Second-Line Medications

• Mineralocorticoid Receptor Antagonists (MRAs): Spironolactone may be considered to decrease hospitalizations, particularly in patients with LVEF on the lower end of the preserved spectrum (closer to 50%) 1
• Angiotensin Receptor-Neprilysin Inhibitors (ARNi): Sacubitril/valsartan may be considered to decrease hospitalizations, particularly in patients with LVEF on the lower end of the preserved spectrum 1
• Angiotensin Receptor Blockers (ARBs): Candesartan may be considered to decrease hospitalizations, particularly in patients with LVEF on the lower end of the preserved spectrum 1

Management of Comorbidities

• Hypertension: Aggressive blood pressure control is recommended to attain targets in accordance with published guidelines 1
• Atrial Fibrillation: Management of AF is useful to improve symptoms in patients with HFpEF 1
• Diabetes: Metformin is recommended as first-line oral hypoglycemic therapy in patients with diabetes and HFpEF 1

Medications to Avoid

• Nitrates or Phosphodiesterase-5 inhibitors: Routine use to increase activity or quality of life is ineffective 1
• Diltiazem or Verapamil: Not recommended in combination with beta-blockers in patients with AF 1
• Thiazolidinediones: Associated with increased risk of HF and should be avoided 1
• Saxagliptin: Associated with increased risk of HF hospitalization and should be avoided 1

Practical Approach to Medication Selection

1. Start with SGLT2 inhibitors: Begin with empagliflozin or dapagliflozin regardless of diabetes status 1, 2
2. Add diuretics for congestion: Use loop diuretics (furosemide, torsemide) to manage volume overload and improve symptoms 1, 3
3. Consider MRAs, ARNis, or ARBs: Add these agents based on individual patient characteristics, particularly for those with LVEF closer to 50% 1
4. Manage comorbidities: Aggressively treat hypertension, diabetes, obesity, and atrial fibrillation 1

Special Considerations

• Beta-blockers: May be used in patients with specific indications such as prior myocardial infarction (for up to 3 years), angina, or atrial fibrillation, but monitor exercise tolerance due to potential for chronotropic incompetence 1
• Renal function: Monitor renal function and electrolytes regularly when using diuretics, MRAs, and SGLT2 inhibitors 4
• Phenotype-directed approach: Consider tailoring therapy based on specific HFpEF phenotypes (e.g., obesity-related, hypertensive, right ventricular dysfunction) 5, 6

Emerging Therapies

• Glucagon-like peptide-1 receptor agonists: Showing promise in patients with HFpEF, particularly those with obesity and diabetes 5
• Non-steroidal MRAs: Under investigation for HFpEF with potentially fewer side effects than traditional MRAs 5

The landscape of HFpEF treatment has evolved significantly in recent years, with SGLT2 inhibitors emerging as the cornerstone of therapy based on robust evidence from clinical trials. A comprehensive approach that includes disease-modifying medications, diuretics for symptom management, and targeted treatment of comorbidities offers the best strategy for improving outcomes in this challenging patient population.