How do SGLT2 (sodium-glucose cotransporter 2) inhibitors help Heart Failure with reduced Ejection Fraction (HFrEF)?

SGLT2 Inhibitors in Heart Failure with Reduced Ejection Fraction (HFrEF)

SGLT2 inhibitors significantly reduce cardiovascular mortality and heart failure hospitalizations in patients with HFrEF and should be prescribed to all eligible patients with HFrEF as part of quadruple therapy regardless of diabetes status. 1, 2

Mechanism of Action and Benefits

SGLT2 inhibitors provide multiple benefits for patients with HFrEF:

• Reduce the combined risk of cardiovascular death or hospitalization for heart failure by approximately 25% 3
• Benefits appear early (within weeks) after initiation 1
• Reduce risk of:
  • Cardiovascular death (14% reduction) 3
  • All-cause mortality (13% reduction) 3
  • Heart failure hospitalizations (26% reduction) 3
  • Renal outcomes (38% reduction) 3

Clinical Application in HFrEF

Patient Selection

• Indicated for adults with heart failure to reduce risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visits 4
• Effective across the spectrum of HFrEF patients, including:
  • With or without diabetes 1, 3
  • Elderly patients 1
  • Patients with recent heart failure hospitalization 1
  • Across various NYHA functional classes (greatest benefit in class II-III) 1

Dosing and Administration

• Recommended dosing:
  • Dapagliflozin: 10 mg once daily 1
  • Empagliflozin: 10 mg once daily 1
• No dose titration required - standard dosing applies to all eligible patients 1
• Can be initiated in-hospital or outpatient setting 2

Renal Considerations

• Safe and effective in patients with eGFR ≥25 mL/min/1.73m² 1
• Should not be initiated if eGFR <25 mL/min/1.73m² 1
• Provides long-term kidney protection 1

Integration with Other HF Therapies

SGLT2 inhibitors should be part of quadruple therapy for HFrEF, along with:

• ACE inhibitors/ARNIs
• Beta-blockers
• Mineralocorticoid receptor antagonists (MRAs)

Key points:

• Benefits are fully additive to effects of other guideline-directed medical therapies 2
• Consistent magnitude of incremental benefit regardless of background therapy quality 2
• Should be prioritized above dose escalation of other therapies to maximize clinical event reduction 2

Implementation Considerations

In-Hospital Initiation

• In-hospital initiation is recommended to improve medication adherence and reduce post-discharge events 2
• Deferring initiation to outpatient setting may expose patients to excess risk of early post-discharge clinical worsening 2
• Current outpatient prescription rates remain suboptimal (only 15.7% of eligible patients receive SGLT2 inhibitors at discharge despite 94.8% being eligible) 5

Monitoring and Safety

• Common adverse effects:
  • Genital mycotic infections
  • Urinary tract infections
  • Volume depletion/hypotension
  • Euglycemic diabetic ketoacidosis (rare but serious) 1
• Withhold for at least 3 days before major surgery requiring prolonged fasting 1
• For patients with diabetes: consider reducing daily insulin dose by 20% and stopping sulfonylureas if hemoglobin A1c <8.5% 2

Special Populations

SGLT2 inhibitors are also beneficial in:

• Heart failure with mildly reduced ejection fraction (HFmrEF, LVEF 41-49%) 2
• Heart failure with preserved ejection fraction (HFpEF, LVEF >50%) 6
• Patients with chronic kidney disease 4

Conclusion

The 2022 AHA/ACC/HFSA guidelines strongly recommend SGLT2 inhibitors for patients with HFrEF to reduce heart failure hospitalizations and cardiovascular mortality 2. Despite strong evidence supporting their use, these medications remain significantly underprescribed 5. Clinicians should prioritize initiating SGLT2 inhibitors in all eligible HFrEF patients to improve outcomes.