What are the recommended medications for a patient with chronic heart failure with preserved ejection fraction (HFpEF)?

Chronic HFpEF Medication Management

SGLT2 inhibitors (dapagliflozin 10 mg daily or empagliflozin 10 mg daily) are the first-line disease-modifying therapy for all patients with chronic HFpEF, regardless of diabetes status, and should be initiated immediately. 1

First-Line Disease-Modifying Therapy

• Start dapagliflozin 10 mg once daily or empagliflozin 10 mg once daily as the cornerstone of treatment 1, 2
• Dapagliflozin reduced worsening heart failure and cardiovascular death by 18% (HR 0.82,95% CI 0.73-0.92) and heart failure hospitalizations by 23% (HR 0.77,95% CI 0.67-0.89) in the DELIVER trial 1, 2
• Empagliflozin reduced heart failure hospitalization or cardiovascular death by 21% (HR 0.79,95% CI 0.69-0.90) in EMPEROR-PRESERVED 1, 2
• These benefits occur independent of glucose-lowering effects and apply to patients with and without diabetes 2
• Ensure eGFR >30 mL/min/1.73m² for dapagliflozin and >60 mL/min/1.73m² for empagliflozin before initiation 1

Symptom Management with Diuretics

• Use loop diuretics at the lowest effective dose to manage congestion and relieve dyspnea 1, 2
• Start furosemide 20-40 mg daily (or bumetanide 0.5-1.0 mg, or torsemide 5-10 mg) and titrate based on symptoms, weight, and volume status 2
• Train patients to self-adjust diuretic doses based on daily weight monitoring to maintain euvolemia 2
• Avoid excessive diuresis, which leads to hypotension, renal dysfunction, and reduced cardiac output—particularly problematic in HFpEF where cardiac output is already compromised 1, 2
• If inadequate response despite dose increases, consider switching to a different loop diuretic or adding a thiazide for sequential nephron blockade 1

Additional Pharmacological Options for Selected Patients

Mineralocorticoid Receptor Antagonists (Spironolactone)

• Consider adding spironolactone 12.5-25 mg daily (titrating to 50 mg) particularly if LVEF is in the lower preserved range (40-50%) 1, 2
• Spironolactone has a Class 2b recommendation based on the TOPCAT trial showing reduction in heart failure hospitalizations (HR 0.83,95% CI 0.69-0.99) but no significant mortality benefit 1, 2
• Monitor potassium and renal function closely—check within 1 week of initiation and after dose changes, as hyperkalemia is a significant risk 2

Sacubitril/Valsartan (ARNI)

• Sacubitril/valsartan may be considered specifically for women and patients with LVEF 45-57%, as these subgroups showed benefit in PARAGON-HF post-hoc analyses 1, 2
• The PARAGON-HF trial did not achieve a significant reduction in the primary composite endpoint overall (rate ratio 0.87; 95% CI 0.75-1.01; p=0.06) 1
• This carries a Class 2b recommendation, indicating it "may be considered" for selected patients 1

Blood Pressure Management

• Target blood pressure <130/80 mmHg using medications already prescribed for heart failure 1, 2
• The SGLT2 inhibitor, loop diuretic, and potentially MRA will contribute to blood pressure control 2
• ACE inhibitors or ARBs are reasonable for additional blood pressure control if needed, though they have not shown mortality benefit in HFpEF specifically 1, 2
• Beta-blockers may be used for blood pressure control and are reasonable in HFpEF, particularly if atrial fibrillation is present for rate control 2

Non-Pharmacological Interventions

• Prescribe supervised exercise training programs (Class 1 recommendation) to improve functional capacity and quality of life 1, 2
• Exercise training typically involves 3 sessions per week for 1-8 months at 40-90% of exercise capacity, using walking, stationary cycling, or high-intensity interval training 1
• Recommend dietary sodium restriction to <2-3 g/day to help control volume status and reduce congestion 2

Management of Comorbidities

• Optimize management of hypertension, diabetes, obesity, and atrial fibrillation, which significantly impact outcomes in HFpEF 1, 2
• For diabetes, prioritize SGLT2 inhibitors (already prescribed for HFpEF), then add GLP-1 receptor agonists if additional glucose lowering is needed 2
• For atrial fibrillation, prescribe anticoagulation based on CHA₂DS₂-VASc score and use beta-blockers cautiously for rate control if COPD is present 3

Critical Medications to Avoid

• Do not use diltiazem or verapamil (nondihydropyridine calcium channel blockers), as they increase the risk of heart failure worsening and hospitalization 4, 1
• Avoid nitrates, as they are associated with a signal of harm in HFpEF 1
• Avoid or use pioglitazone with extreme caution, as thiazolidinediones cause fluid retention and can worsen heart failure 2
• The addition of an ARB to the combination of an ACE inhibitor and an MRA is not recommended because of increased risk of renal dysfunction and hyperkalemia 4

Monitoring and Follow-Up

• Regularly assess volume status, renal function, electrolytes (especially potassium), and symptoms at each visit 1, 3, 2
• Adjust diuretic doses based on congestion status to avoid overdiuresis leading to hypotension and renal dysfunction 2
• Consider wireless, implantable pulmonary artery monitors in selected patients for optimizing volume status 1

Important Clinical Context

No pharmacological agent has been definitively shown to reduce mortality in HFpEF 1. The goal of therapy is to alleviate symptoms, improve quality of life, and reduce hospitalizations 1. SGLT2 inhibitors provide the strongest evidence for reducing heart failure hospitalizations and composite cardiovascular outcomes, making them the clear first-line choice 1, 2.