What is the effectiveness of Dapagliflozin (SGLT2 inhibitor) for treating Heart Failure with preserved Ejection Fraction (HFpEF)?

Dapagliflozin is Effective for Treating Heart Failure with Preserved Ejection Fraction

Dapagliflozin significantly improves symptoms, physical function, and reduces the risk of hospitalization and cardiovascular death in patients with heart failure with preserved ejection fraction (HFpEF), making it a first-line therapy for this condition. 1, 2

Efficacy of Dapagliflozin in HFpEF

Dapagliflozin has demonstrated robust clinical benefits in HFpEF:

• In the DELIVER trial, dapagliflozin reduced the combined risk of worsening heart failure or cardiovascular death by 18% (HR 0.82; 95% CI 0.73-0.92; P<0.001) in patients with heart failure and LVEF >40% 3
• The PRESERVED-HF trial showed that dapagliflozin significantly improved both symptoms and physical limitations, as well as objective measures of exercise function in patients with chronic HFpEF 1
• Dapagliflozin improved the Kansas City Cardiomyopathy Questionnaire Clinical Summary score by 5.8 points at 12 weeks and increased the 6-minute walk distance by 8.2% 1
• Benefits were consistent regardless of diabetes status, making it appropriate for all HFpEF patients 1, 3

Clinical Application Algorithm

1. Patient Selection:

   • Patients with heart failure and LVEF >40%
   • With or without diabetes
   • eGFR ≥30 mL/min/1.73m² (for eGFR 20-30 mL/min/1.73m², dapagliflozin remains the only SGLT2 inhibitor option) 4

2. Dosing:

   • Dapagliflozin 10 mg once daily 2
   • No dose adjustment needed based on diabetes status 4

3. Monitoring:

   • If patient is on insulin or sulfonylureas, monitor for hypoglycemia 4
   • Watch for volume depletion/hypotension, especially during initiation 4
   • Monitor for genital mycotic infections and urinary tract infections 4

4. Expected Outcomes:

   • Reduction in heart failure hospitalizations by 23% (HR 0.77; 95% CI 0.67-0.89) 2
   • Improvement in quality of life and exercise capacity 1
   • Reduction in total heart failure events and symptom burden 3

Comparative Effectiveness

While both dapagliflozin and empagliflozin have shown benefits in HFpEF, dapagliflozin has more robust evidence specifically for symptom improvement and quality of life:

• Dapagliflozin demonstrated significant improvements in symptoms, physical limitations, and exercise function in the PRESERVED-HF trial 1
• Empagliflozin reduced the primary outcome of cardiovascular death or hospitalization for heart failure by 21% in EMPEROR-Preserved 1
• The benefits of SGLT2 inhibitors in HFpEF appear to be a class effect, but dapagliflozin has more comprehensive data on quality of life improvements 5

Important Considerations and Cautions

• Safety profile: Dapagliflozin has a favorable safety profile with similar incidence of adverse events compared to placebo 3
• Potential side effects: Monitor for genital mycotic infections, urinary tract infections, and volume depletion 4
• Rare but serious risk: Euglycemic diabetic ketoacidosis, particularly in situations of insulin dose reduction, prolonged fasting, or carbohydrate restriction 4
• Consistent benefit across subgroups: Efficacy is maintained regardless of age, sex, baseline ejection fraction (including LVEF ≥60%), and diabetes status 3

Implementation in Clinical Practice

Dapagliflozin should be incorporated into standard heart failure therapy for HFpEF patients, alongside:

• Diuretics for symptom relief as needed 4
• Evidence-based beta blockers 4
• Consider ACEi, ARB, or ARNI for patients with LVEF 41-49% (HFmrEF) 4
• Mineralocorticoid receptor antagonists for patients with poorly controlled hypertension 4

The American College of Cardiology/American Heart Association guidelines now include a Class 2a recommendation for SGLT2 inhibitors in HFpEF, recognizing their important role in this previously difficult-to-treat condition 1.