Are there other medications besides Jardiance (empagliflozin) in its class used to treat heart failure with reduced ejection fraction?

SGLT2 Inhibitors for Heart Failure: Beyond Jardiance (Empagliflozin)

Yes, there are multiple SGLT2 inhibitors besides Jardiance (empagliflozin) that are effective for treating heart failure with reduced ejection fraction, with dapagliflozin being the other major medication in this class approved for this indication. 1, 2

Available SGLT2 Inhibitors for Heart Failure

SGLT2 inhibitors (sodium-glucose cotransporter-2 inhibitors) have emerged as a cornerstone therapy for heart failure management. The two primary medications in this class with robust evidence for heart failure treatment are:

1. Empagliflozin (Jardiance)

   • Approved for heart failure across all ejection fraction ranges 2
   • Demonstrated 21% reduction in the composite outcome of cardiovascular death or hospitalization for heart failure in the EMPEROR-Reduced trial 3
   • Effective in patients with eGFR ≥20 mL/min/1.73 m² 2

2. Dapagliflozin (Farxiga)

   • Also approved for heart failure treatment 4
   • Demonstrated 18% reduction in the composite outcome of cardiovascular death or hospitalization for heart failure 4
   • Can be used in patients with eGFR ≥25 mL/min/1.73 m² 2, 4

Efficacy Across the Ejection Fraction Spectrum

Both empagliflozin and dapagliflozin have shown efficacy across different heart failure phenotypes:

• Heart Failure with Reduced Ejection Fraction (HFrEF):

  • Empagliflozin reduced cardiovascular death or hospitalization for heart failure by 25% in patients with LVEF ≤40% 3
  • Dapagliflozin showed similar benefits in the DAPA-HF trial 4

• Heart Failure with Preserved Ejection Fraction (HFpEF):

  • Empagliflozin reduced the primary composite outcome by 21% in the EMPEROR-Preserved trial 5
  • Dapagliflozin showed an 18% reduction in the DELIVER trial 4

• Across the Spectrum:

  • A pooled analysis showed that empagliflozin's benefits were consistent in patients with ejection fractions from <25% to <65%, with some attenuation of effect in those with EF ≥65% 6

Unique Characteristics of SGLT2 Inhibitors

SGLT2 inhibitors have several advantages in heart failure management:

• Do not affect blood pressure, heart rate, or potassium levels 1
• Require no dose adjustment or up-titration 1
• Offer long-term kidney protection despite initial mild eGFR drop 1
• Show benefits within weeks of initiation 1
• Effective regardless of age, sex, or background medical therapy 1
• May reduce the need for diuretic intensification 7
• May facilitate the use of mineralocorticoid receptor antagonists (MRAs) by reducing the risk of severe hyperkalemia 1

Implementation in Heart Failure Treatment

According to the 2021 ESC guidelines and 2022 AHA/ACC/HFSA guidelines, SGLT2 inhibitors are now considered core treatments for heart failure, particularly HFrEF 1:

• Should be added to standard guideline-directed medical therapy including:
  • ACE inhibitors/ARBs/ARNI
  • Beta-blockers
  • Mineralocorticoid receptor antagonists
  • Diuretics (as needed for congestion)

Dosing and Monitoring

• Standard dosing:

  • Empagliflozin: 10 mg once daily 2
  • Dapagliflozin: 10 mg once daily 2, 4

• Key monitoring considerations:

  • Renal function and volume status before initiation
  • Risk of genital mycotic infections (most common side effect)
  • Withhold for at least 3 days before major surgery 2

Clinical Pearls and Pitfalls

• Benefits occur early (within weeks) after initiation 1
• Effectiveness maintained in vulnerable populations including elderly and those with recent heart failure hospitalization 1
• Monitor for genital tract infections, which are more common with SGLT2 inhibitors 8, 3
• These medications should be continued indefinitely as part of heart failure management 2

SGLT2 inhibitors represent a major advance in heart failure therapy, with both empagliflozin and dapagliflozin showing significant benefits in reducing mortality and hospitalizations across the spectrum of heart failure.