What is the creatinine cut-off for initiating Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors in patients with Congestive Heart Failure (CHF)?

From the Guidelines

SGLT2 inhibitors can be initiated in patients with congestive heart failure who have an estimated glomerular filtration rate (eGFR) ≥ 20 mL/min/1.73m², which corresponds to a creatinine threshold that varies based on age, sex, and race.

Key Considerations

• For most heart failure patients, SGLT2 inhibitors like dapagliflozin (Farxiga) 10mg daily or empagliflozin (Jardiance) 10mg daily can be started and continued until dialysis or transplantation is needed, as supported by the findings of the EMPEROR trials 1.
• These medications should be temporarily held during acute illness, especially when patients are at risk for dehydration.
• The benefit of SGLT2 inhibitors in heart failure is independent of their glucose-lowering effect and appears to work through multiple mechanisms including improved cardiac energetics, reduced cardiac preload and afterload, and cardiorenal protective effects.
• Regular monitoring of kidney function is recommended after initiation, particularly in patients with more advanced kidney disease, though the risk of acute kidney injury is relatively low when appropriate precautions are taken, as noted in the standards of care for diabetes management in chronic kidney disease 1.

Important Safety Information

• SGLT2 inhibitors have been associated with a reversible decline in eGFR, but this generally does not require drug discontinuation, and they appear to protect patients from acute kidney injury (AKI) 1.
• Hypovolemia and hypoglycemia may occur with SGLT2 inhibitors, but absolute risks are low, especially at low eGFR, and adjustment of background therapies is generally not required when initiating an SGLT2 inhibitor, but it may be prudent in some patients 1.
• Genital mycotic infections are a known complication of SGLT2 inhibitors, and daily hygienic measures may lessen this risk 1.

Clinical Evidence

• The DAPA-CKD trial provided clear evidence of efficacy and safety for dapagliflozin in patients with eGFR ≥25 mL/min/1.73m² and albuminuria ≥200 mg/g, and subgroup analyses supported the use of SGLT2 inhibitors in patients with baseline eGFR <30 mL/min/1.73m² 1.
• The EMPEROR trials demonstrated the efficacy and safety of empagliflozin among patients with eGFR ≥20 mL/min/1.73m² and heart failure, providing further support for the use of SGLT2 inhibitors in this population 1.

From the FDA Drug Label

In patients with volume depletion, correct this condition before initiating INVOKANA Adult patients taking INVOKANA with albuminuria greater than 300 mg/day may continue INVOKANA 100 mg once daily to reduce the risk of ESKD, doubling of serum creatinine, CV death, and hospitalization for heart failure Table 1: Recommended Dosage in Adults and Pediatric Patients Aged 10 Years and Older with Renal Impairment Estimated Glomerular Filtration Rate [eGFR (mL/min/1. 73 m 2)] Recommended Dosage eGFR 30 to less than 60 The maximum recommended dosage is 100 mg orally once daily eGFR less than 30 Initiation is not recommended

The creatinine cut-off for initiating SGLT2 inhibitors, such as canagliflozin, in patients with CHF is an eGFR of 30 mL/min/1.73 m^2 or greater.

• For patients with an eGFR of 30 to less than 60 mL/min/1.73 m^2, the maximum recommended dosage is 100 mg orally once daily.
• For patients with an eGFR less than 30 mL/min/1.73 m^2, initiation of canagliflozin is not recommended 2. However, adult patients taking canagliflozin with albuminuria greater than 300 mg/day may continue canagliflozin 100 mg once daily to reduce the risk of ESKD, doubling of serum creatinine, CV death, and hospitalization for heart failure 2.

From the Research

Creatinine Cut-Off for SGLT2-Inhibitors in Patients with CHF

• The studies provided do not specify a clear creatinine cut-off for initiating Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors in patients with Congestive Heart Failure (CHF) 3, 4, 5, 6, 7.
• However, the studies suggest that SGLT2 inhibitors can be effective and well-tolerated in patients with CHF across a wide range of estimated glomerular filtration rates (eGFR) 3, 4, 5, 6, 7.
• One study found that patients with an eGFR <25 mL/min/1.73 m2 had a higher risk of cardiovascular outcomes, but still appeared to benefit from continuation of dapagliflozin with no excess in safety outcomes 4.
• Another study found that SGLT2 inhibitors reduced the composite of cardiovascular mortality or heart failure hospitalizations/urgent visits across subgroups of patients with different eGFR levels, including those with an eGFR <60 mL/min/1.73 m2 5.
• The EMPEROR-Reduced and DAPA-HF trials found that SGLT2 inhibitors reduced the combined risk of cardiovascular death or hospitalization for heart failure in patients with heart failure with reduced ejection fraction (HFrEF), regardless of diabetes status or eGFR level 6, 7.

Key Findings

• SGLT2 inhibitors can be effective and well-tolerated in patients with CHF across a wide range of eGFR levels 3, 4, 5, 6, 7.
• Patients with lower eGFR levels may still benefit from SGLT2 inhibitors, but may require closer monitoring due to a higher risk of cardiovascular outcomes 4.
• The decision to initiate SGLT2 inhibitors in patients with CHF should be based on individual patient characteristics and clinical judgment, rather than a specific creatinine cut-off 3, 4, 5, 6, 7.