Is dapagliflozin (SGLT2 inhibitor) indicated in Heart Failure with preserved Ejection Fraction (HFpEF)?

Dapagliflozin in Heart Failure with Preserved Ejection Fraction (HFpEF)

Dapagliflozin is strongly indicated for patients with heart failure with preserved ejection fraction (HFpEF), regardless of diabetes status, to reduce the risk of hospitalization for heart failure and cardiovascular death. 1, 2

Evidence Supporting Dapagliflozin in HFpEF

The 2022 AHA/ACC/HFSA guideline provides a Class 2a recommendation (moderate strength) for SGLT2 inhibitors in HFpEF, supporting their use for improving symptoms, physical function, and reducing hospitalization and cardiovascular death 1. This recommendation is based on robust clinical evidence from large randomized controlled trials.

The DELIVER trial specifically evaluated dapagliflozin in patients with HFpEF (LVEF >40%) and demonstrated that:

• 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) 1, 3
• The primary benefit was driven by a reduction in heart failure hospitalizations 3
• Benefits were consistent regardless of diabetes status 4

Dosing and Patient Selection

• Recommended dose: 10 mg orally once daily 1, 2
• Patient eligibility: Adults with heart failure and LVEF >40%, with or without diabetes 1
• Renal function considerations:
  • For patients with eGFR 20-30 mL/min/1.73m², dapagliflozin remains the only SGLT2 inhibitor option 1
  • For patients with eGFR ≥30 mL/min/1.73m², either dapagliflozin or empagliflozin is appropriate 1

Clinical Benefits in HFpEF

Dapagliflozin provides several important clinical benefits in HFpEF patients:

• Reduces the risk of hospitalization for heart failure 1, 3
• Improves symptoms and physical function 1
• Improves Kansas City Cardiomyopathy Questionnaire Clinical Summary score by 5.8 points at 12 weeks 1
• Increases 6-minute walk distance by 8.2% 1
• Provides benefits across the spectrum of glycemic status (normoglycemia, prediabetes, and type 2 diabetes) 4

Practical Implementation

Dapagliflozin should be considered first-line therapy for HFpEF regardless of diabetes status 1. Implementation of dapagliflozin in eligible HFpEF patients could translate to:

• Absolute risk reduction of 1.3% for mortality 5
• Absolute risk reduction of 5.1% for heart failure readmission 5

Monitoring and Safety Considerations

Key monitoring needs for patients on dapagliflozin include:

• Genital mycotic infections and urinary tract infections 1
• Volume depletion/hypotension 1
• Risk of euglycemic diabetic ketoacidosis (rare but serious), particularly with insulin dose reduction, prolonged fasting, or carbohydrate restriction 1
• Consider discontinuing dapagliflozin at least 3 days before planned surgery to prevent postoperative ketoacidosis 1

Integration with Other HFpEF Therapies

Dapagliflozin can be used alongside other therapies based on comorbidities:

• Diuretics for volume management
• Blood pressure control with RAAS antagonists
• Mineralocorticoid receptor antagonists (MRAs)
• Evidence-based beta blockers 1

When used in patients with well-controlled HbA1c or history of hypoglycemic events, consider weaning or stopping sulfonylureas or glinides to prevent hypoglycemia 1.

Conclusion

The evidence strongly supports the use of dapagliflozin in patients with HFpEF to reduce hospitalizations and improve quality of life. This recommendation is consistent across patients with different glycemic statuses and represents a significant advance in the management of HFpEF, which has historically had limited treatment options.