What medications are used to treat Heart Failure with Preserved Ejection Fraction (HFpEF)?

Medication Treatment for Heart Failure with Preserved Ejection Fraction (HFpEF)

SGLT2 inhibitors (dapagliflozin or empagliflozin) should be the first-line disease-modifying therapy for most patients with HFpEF due to their significant reductions in heart failure hospitalizations and composite cardiovascular outcomes. 1

First-Line Disease-Modifying Therapy

• SGLT2 inhibitors have demonstrated significant reductions in heart failure hospitalizations and cardiovascular outcomes in patients with HFpEF in major clinical trials 1
• Dapagliflozin showed a 23% reduction in heart failure hospitalizations (HR: 0.77; 95% CI: 0.67-0.89) in the DELIVER trial 1
• Ensure eGFR >30 mL/min/1.73 m² for dapagliflozin and >60 mL/min/1.73 m² for empagliflozin before initiation 2
• SGLT2 inhibitors have a Class 2a recommendation for HFpEF patients, indicating they "can be beneficial in decreasing HF hospitalizations and cardiovascular mortality" 1

Symptom Management with Diuretics

• Loop diuretics should be used at the lowest effective dose to manage fluid retention and relieve congestion 2
• Initial diuretic dose depends on multiple factors, including renal function and prior exposure to diuretic therapy 2
• Titrate diuretic dose based on symptoms and volume status, aiming to achieve and maintain euvolemia (the patient's 'dry weight') 2
• If high doses of loop diuretics (equivalent to 80 mg of furosemide twice daily) are needed, consider changing to a different loop diuretic or adding a thiazide diuretic 2
• Monitor blood pressure, electrolytes, and renal function after initiation and during titration 2

Additional Pharmacological Options

• Mineralocorticoid receptor antagonists (MRAs) like spironolactone may be considered, particularly in patients with LVEF in the lower range of preservation (40-50%) 1
• Spironolactone has a Class 2b recommendation, indicating it "may be considered to decrease hospitalizations, particularly among patients with LVEF on the lower end of this spectrum" 1
• When prescribing spironolactone, carefully monitor potassium, renal function, and diuretic dosing to minimize the risk of hyperkalemia 1
• Consider sacubitril/valsartan (ARNI) for selected patients, especially women and those with LVEF in the lower preserved range (45-57%) 1

Management of Comorbidities

• Optimize blood pressure control to target <130/80 mmHg using appropriate antihypertensive medications 1
• For patients with atrial fibrillation, rate control is generally the preferred initial strategy over rhythm control 3
• Beta-blockers are preferred for rate control in HFpEF patients with AF 3
• Non-dihydropyridine calcium channel blockers (diltiazem, verapamil) may be useful for ventricular rate control in patients with AF 2

Treatment Algorithm for HFpEF

1. First-line therapy: SGLT2 inhibitor (dapagliflozin or empagliflozin) 1, 4
2. Symptom management: Loop diuretics for congestion at lowest effective dose 2
3. Consider adding: Spironolactone for patients with LVEF closer to 45-50% 1
4. Consider adding: Sacubitril/valsartan particularly for women and those with LVEF 45-57% 1
5. Optimize comorbidities: Hypertension, diabetes, obesity, and atrial fibrillation 1, 3

Common Pitfalls to Avoid

• Do not treat all HFpEF patients the same as those with reduced ejection fraction, as response to therapies differs significantly 1
• Avoid excessive diuresis leading to hypotension and renal dysfunction 2
• Do not delay initiation of SGLT2 inhibitors which have proven mortality benefits 3
• Monitor for side effects of MRAs, particularly hyperkalemia, especially in patients with reduced renal function 1

Advanced Treatment Options

• Consider referral to an advanced heart failure specialist team for patients with refractory symptoms 1
• Cardiac transplantation can be considered in eligible patients with advanced HFpEF 2

Remember that HFpEF affects approximately 3 million people in the US with an annual mortality rate of approximately 15%, making appropriate treatment essential for improving outcomes 4.