SGLT2 Inhibitors in Heart Failure: The EMPEROR Trial and Beyond
SGLT2 inhibitors should be prescribed for all patients with heart failure, regardless of ejection fraction or diabetes status, as they significantly reduce cardiovascular mortality and heart failure hospitalizations. 1, 2
Efficacy in Heart Failure with Reduced Ejection Fraction (HFrEF)
The EMPEROR-Reduced trial demonstrated that empagliflozin 10 mg daily provides substantial benefits for patients with HFrEF:
- 25% reduction in the primary composite outcome 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 hospitalizations for heart failure (HR 0.70 [95% CI 0.58-0.85]; P<0.001) 3
- Significant slowing of renal function decline (-0.55 vs. -2.28 ml/min/1.73m² per year, P<0.001) 3
- Benefits observed regardless of diabetes status 3
Efficacy in Heart Failure with Preserved Ejection Fraction (HFpEF)
The EMPEROR-Preserved trial extended these benefits to patients with HFpEF (LVEF >40%):
- 21% reduction in the primary composite outcome of cardiovascular death or hospitalization for heart failure (HR 0.79 [95% CI 0.69-0.90]; P<0.001) 1, 4
- 29% reduction in hospitalizations for heart failure 5
- Benefits consistent across patients with or without diabetes 1, 4
- Effects most pronounced in patients with LVEF between 41% and 65% 2
Clinical Practice Guidelines Recommendations
Current guidelines strongly support SGLT2 inhibitor use:
- The American Heart Association/American College of Cardiology recommends SGLT2 inhibitors for all patients with Stage C heart failure with LVEF ≤40% (HFrEF) 1
- SGLT2 inhibitors are also recommended for patients with HFpEF (LVEF >40%), excluding those with NYHA class I symptoms 1
- Benefits appear early (within weeks) and are maintained long-term 2
Practical Implementation
Dosing and Patient Selection
- Recommended dose: Empagliflozin 10 mg once daily or dapagliflozin 10 mg once daily 2
- eGFR requirements: Do not initiate if eGFR <20 mL/min/1.73m² 2
- Perioperative management: Hold for at least 3 days before major surgery or procedures requiring prolonged fasting 2
Monitoring and Adverse Effects
- Monitor for genital mycotic infections and urinary tract infections
- Assess for volume depletion/hypotension, especially when initiating therapy
- Rare but serious: euglycemic diabetic ketoacidosis (particularly in patients with diabetes) 2
Meta-analysis Evidence
A meta-analysis of EMPEROR-Reduced and DAPA-HF trials showed consistent benefits across both medications:
- 13% reduction in all-cause mortality (HR 0.87 [95% CI 0.77-0.98]; p=0.018)
- 14% reduction in cardiovascular death (HR 0.86 [95% CI 0.76-0.98]; p=0.027)
- 26% reduction in the combined risk of cardiovascular death or first hospitalization for heart failure (HR 0.74 [95% CI 0.68-0.82]; p<0.0001) 6
Clinical Pearls and Pitfalls
- Start early: Benefits begin within weeks of initiation 2
- Continue indefinitely: SGLT2 inhibitors should be continued as part of long-term heart failure management 2
- Avoid in: Type 1 diabetes, polycystic kidney disease, or recent immunosuppressive therapy for kidney disease 7
- Caution with: Diuretics (may need dose adjustment due to volume effects)
- Do not withhold based on diabetes status: Benefits are independent of glycemic effects 1, 3
SGLT2 inhibitors represent a breakthrough in heart failure management, with consistent benefits across the spectrum of heart failure that extend beyond their effects on glycemic control.