What is the preferred initial treatment option between Jardiance (empagliflozin) and Forxiga (dapagliflozin) for a patient with impaired renal function and heart failure?

Jardiance (Empagliflozin) vs. Forxiga (Dapagliflozin) for Impaired Renal Function and Heart Failure

Empagliflozin (Jardiance) is the preferred treatment option for patients with impaired renal function and heart failure due to its proven cardiovascular benefits and safety profile across the spectrum of heart failure regardless of ejection fraction. 1

Comparative Efficacy in Heart Failure

• Empagliflozin reduced hospitalization for heart failure by 35% in patients with type 2 diabetes and established cardiovascular disease 2
• Empagliflozin 10mg daily reduced the primary composite outcome of cardiovascular death or hospitalization for heart failure by 21% (HR 0.79 [95% CI 0.69-0.90]; P < 0.001) in patients with heart failure and preserved ejection fraction (HFpEF) 1
• Dapagliflozin 10mg daily reduced the primary composite outcome of worsening heart failure or cardiovascular death by 26% (HR 0.74 [95% CI 0.65-0.85]) in patients with heart failure with reduced ejection fraction (HFrEF) 1
• Both medications have shown benefits in heart failure patients regardless of diabetes status 1

Renal Considerations

• Empagliflozin reduced the risk of a prespecified renal composite outcome by 50% compared to placebo (HR 0.50; 95% CI 0.32-0.77) in patients with prevalent kidney disease 2
• Dapagliflozin has shown renal protective effects in the DAPA-CKD trial, reducing the risk of kidney failure in patients with chronic kidney disease 3
• Empagliflozin is contraindicated in patients with eGFR less than 30 mL/min/1.73 m² and not recommended for initiation when eGFR is below 45 mL/min/1.73 m² 4
• Dapagliflozin had minimal effects on acute eGFR reduction even in recently hospitalized heart failure patients, with no increase in renal adverse events 5

Safety Profile

• Both medications require monitoring for euglycemic ketoacidosis, genital infections, and volume depletion 1
• Empagliflozin may cause acute kidney injury, particularly in settings of reduced oral intake or fluid losses, requiring temporary discontinuation 4
• Empagliflozin increases serum creatinine and decreases eGFR, with patients with hypovolemia being more susceptible to these changes 4
• Dapagliflozin showed consistent benefits in both primary and secondary prevention groups in patients with chronic kidney disease, with low rates of adverse events 3

Recent Evidence and Acute Settings

• Empagliflozin has demonstrated clinical benefit when initiated in patients hospitalized for acute heart failure, regardless of ejection fraction or diabetes status (win ratio 1.36; 95% CI 1.09-1.68; P = 0.0054) 6
• Empagliflozin was well tolerated in the acute heart failure setting with fewer serious adverse events compared to placebo (32.3% vs 43.6%) 6
• The EMPEROR-Reduced study showed that empagliflozin reduced hospitalizations for heart failure complications (13.2% vs 18.3% with placebo) and serious kidney problems (1.6% vs 3.1% with placebo) 7

Clinical Decision Algorithm

1. For patients with eGFR > 45 mL/min/1.73 m²:

   • Empagliflozin 10mg daily is preferred due to strong evidence in both HFrEF and HFpEF 1
   • Monitor renal function regularly and assess for volume status 4

2. For patients with eGFR 30-45 mL/min/1.73 m²:

   • Consider dapagliflozin which has shown benefits in patients with lower eGFR 3
   • More frequent monitoring of renal function is recommended 4

3. For patients with eGFR < 30 mL/min/1.73 m²:

   • Both medications are contraindicated; consider alternative heart failure therapies 4

Practical Considerations

• Start with empagliflozin 10mg once daily, taken in the morning, with or without food 2
• No dose titration is needed for cardiovascular or renal risk reduction benefits 2
• Consider reducing doses of insulin or insulin secretagogues when initiating therapy to reduce risk of hypoglycemia 4
• Discontinue at least 3 days before planned surgery to prevent postoperative ketoacidosis 4
• Monitor for signs of volume depletion, especially when combined with diuretics 4