What is the role of SGLT2 (sodium-glucose cotransporter 2) inhibitors, such as empagliflozin (Empagliflozin) or canagliflozin (Canagliflozin), in the management of heart failure, particularly in patients with reduced ejection fraction?

SGLT2 Inhibitors in Heart Failure Management

SGLT2 inhibitors (empagliflozin and dapagliflozin) are strongly recommended as first-line therapy for heart failure across the entire spectrum of ejection fractions, regardless of diabetes status, to reduce hospitalization for heart failure and cardiovascular mortality. 1, 2

Role in Heart Failure with Reduced Ejection Fraction (HFrEF)

• SGLT2 inhibitors are part of quadruple first-line therapy for HFrEF alongside:

  • ACE inhibitor/ARB/ARNI
  • Evidence-based beta-blocker
  • Mineralocorticoid receptor antagonist (MRA)
  • SGLT2 inhibitor (empagliflozin 10mg daily or dapagliflozin 10mg daily) 1, 2

• In the EMPEROR-Reduced trial, empagliflozin demonstrated:

  • 25% reduction in the combined risk of cardiovascular death or hospitalization for heart failure (HR 0.75; 95% CI, 0.65-0.86; P<0.001) 3
  • 30% reduction in total heart failure hospitalizations (HR 0.70; 95% CI, 0.58-0.85; P<0.001) 3
  • Benefits observed regardless of diabetes status
  • Significant clinical stability improvements evident as early as 12 days after initiation 4

Role in Heart Failure with Preserved Ejection Fraction (HFpEF)

• SGLT2 inhibitors are recommended as first-line therapy for HFpEF 1, 2
• In the EMPEROR-Preserved trial, empagliflozin showed:
  • 21% reduction in the composite of cardiovascular death or hospitalization for heart failure (HR 0.79; 95% CI, 0.69-0.90; P<0.001) 5
  • Benefits consistent regardless of diabetes status

Role in Heart Failure with Mildly Reduced Ejection Fraction (HFmrEF)

• For patients with HFmrEF (LVEF 41-49%), SGLT2 inhibitors have a Class 2a recommendation (Level of Evidence B-R) 2
• In the EMPEROR-Preserved trial subgroup with LVEF 41-49%, empagliflozin reduced the risk of the primary composite endpoint 2

Dosing and Patient Selection

• Recommended dosing:

  • Empagliflozin: 10mg once daily
  • Dapagliflozin: 10mg once daily

• Patient selection considerations:

  • Appropriate for patients with heart failure regardless of ejection fraction
  • Suitable regardless of diabetes status
  • For patients with eGFR 20-30 mL/min/1.73m², dapagliflozin is the only option
  • For patients with eGFR ≥30 mL/min/1.73m², either dapagliflozin or empagliflozin is appropriate 1

Mechanisms of Benefit

SGLT2 inhibitors provide cardiovascular benefits through multiple mechanisms:

• Reduction in preload and afterload
• Decreased myocardial oxygen demand
• Improved cardiac metabolism
• Reduced cardiac fibrosis
• Natriuretic and diuretic effects without sympathetic nervous system activation 1

Monitoring and Safety

• Key monitoring needs:

  • Genital mycotic infections
  • Urinary tract infections
  • Volume depletion/hypotension
  • Risk of euglycemic diabetic ketoacidosis (rare but serious) 1

• Clinical pearls:

  • Benefits appear early (within 12-28 days) and are sustained 4
  • SGLT2 inhibitors also slow the decline in renal function (-0.55 vs -2.28 mL/min/1.73m² per year with placebo) 3
  • Initiation can be considered during hospitalization for heart failure after stabilization 2

Implementation in Practice

For optimal implementation:

1. Assess patient's current heart failure therapy
2. Add SGLT2 inhibitor regardless of diabetes status
3. Monitor for side effects, particularly genital infections and volume status
4. Consider temporary discontinuation during acute illness or prolonged fasting
5. Continue indefinitely as part of comprehensive heart failure management

SGLT2 inhibitors represent a major advance in heart failure therapy with consistent benefits across the spectrum of ejection fractions and regardless of diabetes status.