Is Jardiance (empagliflozin) effective for treating diastolic heart failure?

Empagliflozin (Jardiance) for Diastolic Heart Failure

Empagliflozin is recommended for patients with diastolic heart failure (heart failure with preserved ejection fraction, HFpEF) to reduce the risk of heart failure hospitalization and cardiovascular death. 1, 2

Efficacy in Diastolic Heart Failure

• The EMPEROR-Preserved trial demonstrated that empagliflozin significantly reduced the primary composite endpoint of cardiovascular death or hospitalization for heart failure by 21% in patients with heart failure with LVEF >40% (HR 0.79; 95% CI 0.69-0.90; p<0.001) 1

• This benefit was primarily driven by a 29% reduction in heart failure hospitalizations, with a non-significant trend toward reduced cardiovascular death 2

• The benefits of empagliflozin were consistent regardless of diabetes status, making it appropriate for patients with diastolic heart failure with or without diabetes 1, 3

• Total hospitalizations for heart failure were significantly lower with empagliflozin (407) compared to placebo (541), representing a 27% reduction (HR 0.73; 95% CI 0.61-0.88; p<0.001) 1

Treatment Algorithm for Diastolic Heart Failure

1. First-line therapy:

   • SGLT2 inhibitors (empagliflozin) are recommended to reduce heart failure hospitalizations and cardiovascular events 2
   • Diuretics for symptom relief in patients with fluid overload 2

2. Additional therapies to consider:

   • Blood pressure control with RAAS blockers (ACEi, ARB) as first-line agents, especially for patients with hypertension 2
   • MRAs (mineralocorticoid receptor antagonists) may be considered, particularly in patients with LVEF on the lower end of the preserved spectrum 2
   • ARNi (sacubitril/valsartan) may be considered in selected patients, particularly those with LVEF on the lower end of the preserved spectrum 2

3. Avoid:

   • Nitrates or phosphodiesterase-5 inhibitors are ineffective for increasing activity or quality of life in HFpEF 2
   • Thiazolidinediones (pioglitazone, rosiglitazone) are not recommended in heart failure 2
   • Saxagliptin is not recommended in patients with heart failure 2

Mechanism of Action in Diastolic Heart Failure

• Empagliflozin appears to improve diastolic function through several mechanisms: 4
  • Reduction in left ventricular mass
  • Improvement in wall stress
  • Hemodynamic improvements (reduction in preload and afterload)
  • Slowing the decline in estimated glomerular filtration rate over time 2

Special Considerations

• The benefits of empagliflozin in heart failure appear to be a class effect of SGLT2 inhibitors and are independent of their glucose-lowering effects 5, 2

• The efficacy of empagliflozin is consistent across the spectrum of ejection fraction, though there may be slightly less benefit in patients with very high ejection fractions (>62.5%) 2

• Common adverse effects include uncomplicated genital and urinary tract infections and hypotension 1

• Empagliflozin does not lower HbA1c in patients without diabetes and is not associated with increased risk of hypoglycemia in non-diabetic patients 3

Guideline Recommendations

• The 2022 AHA/ACC/HFSA guideline for heart failure management gives a Class 2a recommendation (moderate strength) for SGLT2 inhibitors in HFpEF 2

• The 2020 ESC guidelines on diabetes and cardiovascular diseases recommend SGLT2 inhibitors (including empagliflozin) to lower the risk of heart failure hospitalization in patients with diabetes 2

• The 2024 American Diabetes Association standards of care recommend SGLT2 inhibitors for heart failure risk reduction regardless of diabetes status 2