What is the guideline-directed medical therapy (GDMT) for Heart Failure with preserved Ejection Fraction (HFpEF)?

From the Guidelines

Guideline-directed medical therapy (GDMT) for heart failure with preserved ejection fraction (HFpEF) should include SGLT2 inhibitors, such as empagliflozin or dapagliflozin, as first-line treatments, as they have been shown to reduce hospitalizations and cardiovascular death 1.

Key Components of GDMT for HFpEF

• SGLT2 inhibitors: reduce hospitalizations and cardiovascular death, with a Class of Recommendation 2a 1
• Mineralocorticoid receptor antagonists (MRAs): may be beneficial in selected patients, with a Class of Recommendation 2b 1
• Angiotensin receptor-neprilysin inhibitors (ARNIs): may be considered, with a Class of Recommendation 2b 1
• Blood pressure control: crucial, with ACE inhibitors, ARBs, or ARNIs recommended for hypertensive HFpEF patients
• Diuretics: essential for managing congestion and fluid overload, particularly loop diuretics such as furosemide or torsemide
• Treatment of comorbidities: such as atrial fibrillation, diabetes, obesity, and sleep apnea

Rationale for GDMT in HFpEF

The 2022 AHA/ACC/HFSA guideline for the management of heart failure recommends SGLT2 inhibitors as a first-line treatment for HFpEF, due to their ability to reduce hospitalizations and cardiovascular death 1. Additionally, MRAs and ARNIs may be beneficial in selected patients, and blood pressure control is crucial in hypertensive HFpEF patients. Diuretics are essential for managing congestion and fluid overload, and treatment of comorbidities is also important.

Clinical Considerations

When implementing GDMT for HFpEF, it is essential to consider the individual patient's needs and comorbidities. The treatment should be tailored to address the underlying pathophysiology and symptoms of HFpEF, and to reduce hospitalizations and improve quality of life. Regular monitoring and adjustment of the treatment plan are necessary to ensure optimal outcomes.

From the Research

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

• The management of HFpEF is largely focused on the management of symptoms and comorbidities, as there are no approved treatments specifically indicated for HFpEF 2.
• GDMT is the cornerstone of pharmacological therapy for patients with heart failure with reduced ejection fraction (HFrEF), but its application in HFpEF is less clear 3.
• Recent evidence suggests that sodium-glucose co-transporter 2 inhibitors (SGLT2i) and non-steroidal mineralocorticoid receptor antagonists (MRA) constitute foundational therapy for all eligible patients with HFpEF, with significant clinical benefits within weeks of medication initiation 4.
• The use of GDMT in HFpEF may involve the consideration of adjunctive therapies, such as glucagon-like peptide-1 receptor agonists (GLP-1 RA) for patients with obesity, and angiotensin receptor-neprilysin inhibitors (ARNI) for patients with EF below normal 4.
• The pharmacologic management of HFpEF in older adults requires careful consideration of age-related changes in pharmacokinetics and pharmacodynamics, as well as the concurrence of geriatric conditions such as polypharmacy and frailty 5.

Key Considerations for GDMT in HFpEF

• The use of loop diuretics, mineralocorticoid receptor antagonists (MRAs), and SGLT2 inhibitors may be beneficial for most patients with HFpEF 5.
• Angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors (ARB/ARNIs) and GLP-1RAs may be considered as add-on therapies for some patients, but require careful consideration of the risk of geriatric conditions such as falls, malnutrition, and/or sarcopenia 5.
• Beta blockers may be considered for a smaller subset of patients with HFpEF, but require careful consideration of the potential risks and benefits 5.

Challenges and Limitations

• The diagnosis of HFpEF in the outpatient setting presents unique challenges, including a high burden of comorbidities and difficulties in distinguishing HFpEF from normal aging 2.
• The lack of approved treatments specifically indicated for HFpEF, and the need for careful consideration of the potential risks and benefits of GDMT in this population 2, 6.