What is the recommended medication regimen for a patient with heart failure with preserved ejection fraction (HFpEF) and an ejection fraction of approximately 60%?

Recommended Medication Regimen for Diastolic Heart Failure with Ejection Fraction of 60%

Start with an SGLT2 inhibitor (empagliflozin or dapagliflozin) as first-line disease-modifying therapy, add loop diuretics as needed for congestion, and optimize blood pressure control targeting <130/80 mmHg using your SGLT2 inhibitor and additional antihypertensives if needed. 1, 2

First-Line Disease-Modifying Therapy

SGLT2 inhibitors are the cornerstone of HFpEF treatment and should be initiated immediately:

• Empagliflozin 10 mg daily reduced the composite endpoint of HF hospitalization or cardiovascular death by 21% (HR 0.79,95% CI 0.69-0.90) in EMPEROR-Preserved 1
• Dapagliflozin 10 mg daily reduced worsening HF and cardiovascular death by 18% (HR 0.82,95% CI 0.73-0.92) in DELIVER 1, 2
• These benefits occur regardless of diabetes status and represent a Class 2a recommendation from the 2022 ACC/AHA/HFSA guidelines 1, 2
• At an EF of 60%, you are at the higher end of the preserved spectrum where SGLT2 inhibitors showed slightly attenuated but still meaningful benefit 1

Symptom Management with Diuretics

Loop diuretics should be used at the lowest effective dose to relieve congestion:

• Prescribe furosemide or torsemide only if the patient has signs or symptoms of volume overload (orthopnea, paroxysmal nocturnal dyspnea, peripheral edema, elevated jugular venous pressure) 1, 3
• Titrate diuretic dose based on symptoms and volume status rather than using fixed high doses 2
• If inadequate response despite dose increases, consider switching to a different loop diuretic or adding a thiazide for sequential nephron blockade 2

Blood Pressure Optimization

Target blood pressure <130/80 mmHg using a structured approach:

• RAAS antagonists (ACE inhibitors or ARBs) should be considered as first-line agents for additional blood pressure control beyond the SGLT2 inhibitor, given their experience in HFpEF trials 1
• The SPRINT trial established that intensive blood pressure control significantly reduces HF and cardiovascular outcomes in high-risk patients 1
• Beta-blockers may be used if the patient has a history of MI, symptomatic coronary artery disease, or atrial fibrillation with rapid ventricular response 1
• Avoid nondihydropyridine calcium channel blockers (diltiazem, verapamil) as they have negative inotropic effects and increase risk of HF worsening 2

Additional Pharmacological Considerations

At an EF of 60%, additional agents have limited evidence but may be considered in specific scenarios:

• Mineralocorticoid receptor antagonists (spironolactone 12.5-25 mg daily) have a Class 2b recommendation and may be considered, though benefit is greater in patients with LVEF closer to 50% rather than 60% 1, 2

• Spironolactone reduced HF hospitalizations (HR 0.83) in TOPCAT but did not reduce mortality 1, 2

• If using spironolactone, monitor potassium and renal function carefully at initiation and follow-up to minimize hyperkalemia risk 1

• Angiotensin receptor-neprilysin inhibitors (sacubitril-valsartan) also have a Class 2b recommendation and may be considered, particularly if the patient is female or has LVEF in the lower preserved range (45-57%) 1, 2

• PARAGON-HF did not meet its primary endpoint overall, but showed signals of benefit in these subgroups 1

• At an EF of 60%, sacubitril-valsartan would be a lower priority than in patients with EF closer to 50% 1

Critical Medications to Avoid

Do not prescribe the following as they are ineffective or harmful in HFpEF:

• Nitrates or phosphodiesterase-5 inhibitors are ineffective for increasing activity or quality of life (Class 3: No Benefit recommendation) 1
• Nondihydropyridine calcium channel blockers increase risk of HF worsening and hospitalization 2

Comorbidity Management

Aggressively manage comorbidities as they significantly impact outcomes:

• Control diabetes preferentially with SGLT2 inhibitors given their dual benefit 2, 4
• Manage atrial fibrillation with individualized rate or rhythm control strategies per AF guidelines 1
• Address obesity with supervised exercise training and weight loss interventions 3, 4

Non-Pharmacological Interventions

Prescribe supervised exercise training programs (Class 1 recommendation):

• Exercise training improves aerobic capacity by 12-14% and produces clinically meaningful improvements in quality of life 2
• Typical programs involve 3 sessions per week for 1-8 months at 40-90% of exercise capacity 2

Provide education in HF self-care:

• Teach adherence to medications and dietary sodium restriction 3
• Instruct on monitoring symptoms and vital signs to avoid decompensation 3

Practical Treatment Algorithm

1. Initiate empagliflozin 10 mg daily or dapagliflozin 10 mg daily immediately 1, 2
2. Add loop diuretic (furosemide 20-40 mg daily) only if congested 2, 3
3. Optimize blood pressure to <130/80 mmHg using ACE inhibitor or ARB if needed beyond SGLT2 inhibitor 1, 2
4. Consider spironolactone 12.5-25 mg daily only if patient has additional indications (resistant hypertension, lower EF within preserved range) and monitor potassium closely 1, 2
5. Prescribe supervised exercise training 2
6. Aggressively manage comorbidities (diabetes, obesity, atrial fibrillation) 2, 4

Common Pitfalls to Avoid

• Do not treat HFpEF patients identically to HFrEF patients - the response to therapies differs significantly between these populations 2
• Do not use high-dose diuretics chronically - use the lowest effective dose to maintain euvolemia 2, 3
• Do not overlook comorbidity management - hypertension, diabetes, obesity, and atrial fibrillation significantly impact outcomes 2, 4
• Do not prescribe nitrates or PDE-5 inhibitors - they are ineffective and potentially harmful 1