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

Guideline Medical Therapy for Heart Failure with Preserved Ejection Fraction

SGLT2 inhibitors (dapagliflozin or empagliflozin) are the first-line disease-modifying therapy for HFpEF and should be initiated in all eligible patients, as they reduce heart failure hospitalizations and cardiovascular death by approximately 20%. 1, 2, 3

Core Pharmacological Management

First-Line Disease-Modifying Therapy

SGLT2 Inhibitors (Class 2a Recommendation)

• Dapagliflozin reduces the composite endpoint of worsening heart failure and cardiovascular death (HR 0.82; 95% CI 0.73-0.92) and decreases heart failure hospitalizations by 23% (HR 0.77; 95% CI 0.67-0.89) based on the DELIVER trial 1
• Empagliflozin reduces hospitalization for heart failure and cardiovascular death (HR 0.79; 95% CI 0.69-0.90) based on the EMPEROR-PRESERVED trial 1
• Initiate early in the treatment course to maximize mortality and morbidity benefits 1
• Ensure eGFR >30 mL/min/1.73m² for dapagliflozin and >60 mL/min/1.73m² for empagliflozin before starting 1

Symptom Management with Diuretics

• Loop diuretics (furosemide or torsemide) are the mainstay for managing fluid retention, congestion, orthopnea, and paroxysmal nocturnal dyspnea 1, 2, 3
• Use the lowest effective dose titrated based on symptoms and volume status 1
• For acute presentations with orthopnea/PND, start with 20-40 mg IV furosemide (or equivalent); for patients already on chronic diuretics, use at least the equivalent of their oral dose 1
• If inadequate response despite dose increases, consider switching to a different loop diuretic or adding a thiazide diuretic for sequential nephron blockade 1

Additional Pharmacological Options

Mineralocorticoid Receptor Antagonists (Class 2b Recommendation)

• Spironolactone may be considered to decrease hospitalizations, particularly in patients with LVEF in the lower preserved range (45-50%) 1, 2
• The TOPCAT trial showed spironolactone reduced heart failure hospitalizations (HR 0.83; 95% CI 0.69-0.99) but did not significantly reduce the primary composite outcome 1
• Requires careful monitoring of potassium levels and renal function to minimize hyperkalemia risk 1, 2

Angiotensin Receptor-Neprilysin Inhibitors (Class 2b Recommendation)

• Sacubitril/valsartan may be considered for selected patients, particularly women and those with LVEF 45-57% 1, 2
• The PARAGON-HF trial showed potential benefit in women (rate ratio 0.73; 95% CI 0.59-0.90) and patients with LVEF below the median (rate ratio 0.78; 95% CI 0.64-0.95) 1
• Did not achieve significant reduction in the primary endpoint in the overall HFpEF population 1

Treatment Algorithm

Step 1: Initiate SGLT2 inhibitor (dapagliflozin or empagliflozin) in all eligible patients 1, 2

Step 2: Add loop diuretics as needed to maintain euvolemia and control congestive symptoms 1, 2, 3

Step 3: Consider adding spironolactone if LVEF is in the lower preserved range (45-50%) and patient can be monitored for hyperkalemia 1, 2

Step 4: Consider sacubitril/valsartan for women or patients with LVEF 45-57% who remain symptomatic 1, 2

Management of Comorbidities

• Hypertension: Optimize blood pressure control to target <130/80 mmHg using appropriate antihypertensive medications 1
• Diabetes: Manage with preference for SGLT2 inhibitors given their additional heart failure benefits 1
• Atrial fibrillation: Provide anticoagulation based on CHA₂DS₂-VASc score and consider rate control with cardioselective beta-blockers 4
• Obesity: Prescribe diet-induced weight loss, which produces clinically meaningful increases in functional capacity and quality of life 3
• Aggressive management of all cardiovascular and non-cardiovascular comorbidities is crucial, as they significantly impact outcomes 1, 2

Non-Pharmacological Interventions

• Supervised exercise training programs improve functional capacity and quality of life 1
• Multidisciplinary heart failure programs should be offered to all patients 1
• Salt and fluid restriction with education in heart failure self-care (medication adherence, dietary restrictions, symptom monitoring) helps avoid decompensation 3

Monitoring and Follow-Up

• Regularly assess volume status, renal function, and electrolytes, especially with MRA therapy 1, 4
• Monitor symptoms and functional capacity to guide treatment adjustments 1
• Consider wireless implantable pulmonary artery monitors in selected patients for optimizing volume status 1

Critical Pitfalls to Avoid

• Do not treat HFpEF patients the same as those with HFrEF, as response to therapies differs significantly between these populations 1, 2
• Avoid excessive diuresis, which leads to hypotension, worsening renal function, and electrolyte abnormalities 1, 2
• Do not overlook comorbidity management, which significantly impacts outcomes in HFpEF 1, 2
• Beta-blockers are not recommended as primary HFpEF therapy unless specific indications exist (e.g., rate control for atrial fibrillation, post-myocardial infarction) 2
• Avoid using medications proven only for HFrEF without evidence in HFpEF; focus on evidence-based therapies specific to this population 2

Advanced Treatment Considerations

• Refer patients with advanced HFpEF refractory to standard therapies to an advanced heart failure specialist team 1
• Cardiac transplantation can be considered in eligible patients with advanced HFpEF 1