What is the role of SGLT2 (Sodium-Glucose Linked Transporter 2) inhibitors, such as dapagliflozin (Dapagliflozin) and empagliflozin (Empagliflozin), in treating heart failure with reduced ejection fraction (HFrEF)?

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

SGLT2 inhibitors should be prescribed to all patients with symptomatic heart failure with reduced ejection fraction (HFrEF) with LVEF ≤40%, regardless of diabetes status, as they significantly reduce mortality, hospitalization for heart failure, and improve quality of life. 1, 2

Mechanism and Clinical Benefits

SGLT2 inhibitors work by blocking glucose reabsorption in the kidneys, producing several beneficial cardiovascular effects:

• Reduction in primary composite outcomes:

  • Dapagliflozin: 18% reduction in cardiovascular death or heart failure hospitalization (HR 0.82 [95% CI 0.73–0.92]; P < 0.001) 2, 3
  • Empagliflozin: 21% reduction in cardiovascular death or heart failure hospitalization (HR 0.79 [95% CI 0.69–0.90]; P < 0.001) 2, 3

• Mortality benefits:

  • 13% reduction in all-cause mortality (HR 0.87,95% CI 0.77-0.98; p=0.018) 3
  • 14% reduction in cardiovascular mortality (HR 0.86,95% CI 0.76-0.98; p=0.027) 3

• Additional benefits:

  • 25% decrease in recurrent heart failure hospitalizations 3
  • Renal protection with 38% reduction in composite renal endpoints 3
  • Improvement in quality of life 4

Patient Selection and Dosing

SGLT2 inhibitors are recommended for:

• Patients ≥18 years with Stage C heart failure (current or prior HF symptoms) with LVEF ≤40% 1
• Both inpatient and outpatient settings 1
• Patients already on standard guideline-directed medical therapy (GDMT) 2

Dosing:

• Dapagliflozin: 10 mg once daily 2, 5
• Empagliflozin: 10 mg once daily 2

Contraindications and Precautions

Do not use in patients with:

• eGFR <20 mL/min/1.73 m² 1, 2
• Type 1 diabetes 1, 2
• Heart transplant or LVAD 1

Precautions:

• Withhold for at least 3 days before major surgery or procedures requiring prolonged fasting 2
• Monitor for genital mycotic infections, urinary tract infections, and volume depletion 2
• Rare but serious risk of euglycemic diabetic ketoacidosis 2

Implementation in Clinical Practice

Despite strong evidence supporting their use, SGLT2 inhibitors remain significantly underprescribed. Only 15.7% of eligible HFrEF patients receive these medications at hospital discharge, even though 94.8% are eligible 6.

Practical approach to implementation:

1. Early initiation: Consider as first-line therapy in newly diagnosed HFrEF 4
2. Inpatient initiation: Safe to start during hospitalization for heart failure 5, 4
3. Add to existing therapy: Benefits are independent of background heart failure medications 4
4. No dose titration needed: Unlike many heart failure medications, SGLT2 inhibitors do not require dose adjustment or up-titration 2

Benefits in Special Populations

SGLT2 inhibitors show consistent benefits across multiple subgroups:

• Patients with and without diabetes 1, 2, 3
• Elderly patients 2
• Patients with recent heart failure hospitalization 2
• Across different eGFR levels (above 20 mL/min/1.73 m²) 3

Common Pitfalls to Avoid

1. Delaying initiation: Benefits appear within weeks of starting therapy; early initiation is recommended 2, 4
2. Restricting to diabetic patients only: Benefits extend to non-diabetic patients 1, 2, 3
3. Concerns about hypotension: SGLT2 inhibitors have minimal effects on blood pressure 2, 4
4. Concerns about renal function: These medications provide renal protection rather than harm when used appropriately 2, 4, 3
5. Failure to restart after hospitalization: Resume when the patient is clinically stable and has resumed oral intake 2

SGLT2 inhibitors represent a breakthrough in heart failure management, offering substantial improvements in outcomes with a favorable safety profile. They should be considered a cornerstone therapy for all eligible patients with HFrEF.