Is Jardiance (empagliflozin) appropriate for a patient with Chronic Heart Failure with Reduced Ejection Fraction (CHFrEF) and Chronic Kidney Disease (CKD) stage IV?

Jardiance (Empagliflozin) in CHFrEF with CKD Stage IV

Jardiance is NOT appropriate for a patient with CHFrEF and CKD stage IV (eGFR 15-29 mL/min/1.73 m²) for glycemic control, but may be continued if already established for heart failure benefits, though this represents off-label use below FDA-approved thresholds. 1

FDA-Approved Kidney Function Thresholds

• Empagliflozin is contraindicated when eGFR is <30 mL/min/1.73 m² according to the FDA label, which encompasses CKD stage IV 1
• The FDA label explicitly states that "use of JARDIANCE is not recommended when eGFR is persistently less than 45 mL/min/1.73 m²" 1
• More frequent renal function monitoring is required in patients with eGFR below 60 mL/min/1.73 m² 1

Guideline Recommendations for Heart Failure

Despite FDA restrictions, recent guidelines show evolving evidence:

• The 2024 ESC guidelines recommend SGLT2 inhibitors (dapagliflozin or empagliflozin) for CCS patients with HFrEF to reduce HF hospitalization and death (Class I, Level A recommendation) 2
• The 2022 AHA/ACC/HFSA guidelines give empagliflozin a Class 2a recommendation for HFmrEF (LVEF 41-49%), with benefits extending to patients with lower LVEF 2
• The 2024 multispecialty DCRM guidelines state that empagliflozin improved CKD and reduced cardiovascular events in persons with moderate to severe CKD, including those without diabetes 2

Evidence from Clinical Trials in Advanced CKD

The EMPEROR-Reduced trial provides critical data:

• Empagliflozin reduced cardiovascular death or HF hospitalization consistently across kidney function categories, including patients with eGFR as low as 20 mL/min/1.73 m² 3
• The hazard ratio for the primary outcome was 0.78 (95% CI 0.65-0.93) in patients with CKD and 0.72 (95% CI 0.58-0.90) in those without CKD 3
• Empagliflozin slowed eGFR decline by 1.11 mL/min/1.73 m²/yr in CKD patients and reduced composite kidney outcomes (HR 0.53,95% CI 0.31-0.91) 3
• The drug was well-tolerated in CKD patients, with benefits consistent across the spectrum of kidney impairment 3, 4

Diabetes Guidelines for Advanced CKD

• The 2022 ADA/KDIGO consensus recommends SGLT2 inhibitors for patients with type 2 diabetes and eGFR ≥20 mL/min/1.73 m² to reduce CKD progression and cardiovascular events 2
• Empagliflozin can be started with eGFR >30 mL/min/1.73 m² according to diabetes guidelines, though pivotal trials included participants with eGFR <30 mL/min/1.73 m² 2
• For glycemic control specifically, empagliflozin should be avoided in CKD stage IV as its glucose-lowering efficacy is significantly attenuated at low eGFR 5

Clinical Decision Algorithm

For a patient with CHFrEF and CKD stage IV:

1. If empagliflozin is NOT currently prescribed:

   • Do NOT initiate empagliflozin for glycemic control (contraindicated per FDA) 1
   • Consider initiation ONLY if eGFR is 20-29 mL/min/1.73 m² AND the primary indication is heart failure benefit, recognizing this is below FDA-approved thresholds but supported by trial data 3
   • Ensure patient has stable kidney function and is not acutely ill 1

2. If empagliflozin is ALREADY prescribed:

   • Continue the medication if eGFR is 20-29 mL/min/1.73 m² based on EMPEROR-Reduced protocol, which specified continuation when eGFR fell below initiation thresholds 2, 3
   • Discontinue if eGFR falls below 20 mL/min/1.73 m² or if patient requires dialysis 1

3. Monitor closely for:

   • Volume depletion and acute kidney injury (consider reducing diuretic doses proactively) 2, 1
   • Serum creatinine and eGFR every 1-2 months 1
   • Signs of ketoacidosis, especially during acute illness 1
   • Genital mycotic infections (1.7% incidence) 6

Critical Caveats

• The glycemic benefit of empagliflozin is minimal in CKD stage IV due to reduced glucose filtration; the primary rationale for use would be cardiovascular and renal protection 5
• Temporarily discontinue during acute illness, surgery, or situations causing reduced oral intake or fluid losses 2, 1
• The FDA contraindication at eGFR <30 mL/min/1.73 m² creates a regulatory-evidence gap, as trial data support use down to eGFR 20 mL/min/1.73 m² 1, 3
• Alternative agents for glycemic control in CKD stage IV include DPP-4 inhibitors (with dose adjustment) or GLP-1 receptor agonists (without dose adjustment) 5

Practical Recommendation

For heart failure benefit in stable patients with eGFR 20-29 mL/min/1.73 m²: Empagliflozin may be considered or continued based on EMPEROR-Reduced evidence, but this requires shared decision-making acknowledging off-label use below FDA thresholds 3. For eGFR <20 mL/min/1.73 m² or for glycemic control at any CKD stage IV level: Do not use empagliflozin 1.