What is the preferred SGLT2 (sodium-glucose cotransporter 2) inhibitor for heart failure?

Preferred SGLT2 Inhibitor for Heart Failure

Dapagliflozin or empagliflozin are equally recommended as the preferred SGLT2 inhibitors for heart failure, regardless of ejection fraction or diabetes status. 1

Evidence-Based Recommendation Algorithm

First-Line SGLT2 Inhibitors for Heart Failure

• Dapagliflozin and empagliflozin have the strongest evidence and explicit guideline recommendations for heart failure treatment 1
• Both medications have demonstrated significant benefits in:
  • Reducing hospitalization for heart failure
  • Reducing cardiovascular mortality
  • Improving quality of life

Selection Based on Heart Failure Type

For Heart Failure with Reduced Ejection Fraction (HFrEF, LVEF ≤40%):

• Both dapagliflozin and empagliflozin are recommended as Class I (highest recommendation) treatments 1
• Key evidence:
  • DAPA-HF trial showed dapagliflozin reduced the primary composite outcome of worsening heart failure or cardiovascular death (HR 0.74) 1
  • EMPEROR-Reduced showed similar benefits with empagliflozin 2
  • Meta-analysis of both trials confirmed 13% reduction in all-cause mortality and 14% reduction in cardiovascular death 2

For Heart Failure with Mildly Reduced or Preserved Ejection Fraction (HFmrEF/HFpEF, LVEF >40%):

• Both dapagliflozin and empagliflozin are recommended (Class I recommendation) 1
• Key evidence:
  • EMPEROR-Preserved trial showed empagliflozin reduced the primary composite endpoint of cardiovascular death or hospitalization for heart failure in patients with LVEF >40% 1
  • Benefits were consistent across LVEF subgroups (41-49%, 50-<60%, and >60%) 1

Special Considerations

Acute Heart Failure

• Empagliflozin has specific evidence from the EMPULSE trial showing benefit when initiated during hospitalization for acute heart failure 3
• Patients treated with empagliflozin showed clinical benefit regardless of ejection fraction or diabetes status 3

Safety Considerations

• Monitor for diabetic ketoacidosis, especially in patients with type 1 diabetes or those on insulin with significant dose reductions 1
• Caution in patients with eGFR <20 mL/min/1.73m² 1
• Both medications have similar safety profiles with low rates of serious adverse events 3, 2

Mechanism of Action

Both dapagliflozin and empagliflozin:

• Inhibit SGLT2 in the proximal renal tubules
• Reduce sodium reabsorption
• Increase delivery of sodium to the distal tubule
• Lower both pre- and afterload of the heart
• Downregulate sympathetic activity
• Decrease intraglomerular pressure 4, 5

Common Pitfalls to Avoid

1. Delaying initiation: Guidelines recommend early initiation of SGLT2 inhibitors as part of foundational heart failure therapy 1
2. Restricting use to diabetic patients only: Benefits are consistent regardless of diabetes status 1, 2
3. Stopping during acute decompensation: Evidence supports initiating these medications even during hospitalization for acute heart failure 3
4. Failure to monitor for euglycemic ketoacidosis: This rare but serious complication requires vigilance, especially in patients with type 1 diabetes or insulin dose reductions 1

Summary

Both dapagliflozin and empagliflozin are equally effective first-line SGLT2 inhibitors for heart failure treatment across the spectrum of ejection fractions. The choice between them should be based on specific patient factors, formulary availability, and cost considerations, as their cardiovascular benefits and safety profiles are comparable.