Are Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitors still indicated for heart failure in patients with impaired renal function, specifically those with anuria or oliguria?

From the Guidelines

Yes, SGLT2 inhibitors are still indicated for heart failure even in patients with anuria or oliguria. These medications, including empagliflozin (Jardiance), dapagliflozin (Farxiga), and canagliflozin (Invokana), provide cardiovascular benefits that extend beyond their diuretic effects. For heart failure with reduced ejection fraction (HFrEF), the typical dosing is empagliflozin 10mg daily or dapagliflozin 10mg daily, regardless of kidney function. The benefits in heart failure appear to be independent of the glucose-lowering or diuretic mechanisms. SGLT2 inhibitors reduce heart failure hospitalizations and cardiovascular mortality through multiple pathways including improved cardiac energetics, reduced cardiac fibrosis, decreased cardiac preload and afterload, and anti-inflammatory effects. While these medications do have diuretic properties that may not be relevant in anuric patients, their metabolic and cardioprotective effects persist. However, it's essential to monitor kidney function, as severe kidney impairment (eGFR <20-30 mL/min/1.73m²) may be a limiting factor depending on the specific medication and local prescribing guidelines 1.

Key Considerations

• SGLT2 inhibitors have been shown to reduce heart failure hospitalizations and cardiovascular mortality in patients with heart failure, including those with reduced ejection fraction 1.
• The benefits of SGLT2 inhibitors in heart failure are independent of their diuretic effects and are thought to be due to their metabolic and cardioprotective effects 1.
• Severe kidney impairment (eGFR <20-30 mL/min/1.73m²) may be a limiting factor for the use of SGLT2 inhibitors, but the benefits of these medications can still be observed in patients with lower eGFR levels 1.
• Monitoring of kidney function is essential when using SGLT2 inhibitors, especially in patients with pre-existing kidney disease 1.

Recommendations

• SGLT2 inhibitors should be considered for patients with heart failure, including those with anuria or oliguria, as they provide cardiovascular benefits beyond their diuretic effects 1.
• The selection of specific SGLT2 inhibitors may depend on comorbidity and CKD stage, with empagliflozin and dapagliflozin being recommended for patients with eGFR 25-45 mL/min/1.73m² for kidney/heart failure outcomes 1.
• Patients with type 2 diabetes and CKD should be considered for SGLT2 inhibitor therapy to reduce CKD progression and cardiovascular events, regardless of kidney function 1.

From the Research

SGLT2 Inhibitors in Heart Failure

• SGLT2 inhibitors have been shown to reduce cardiovascular death and heart failure hospitalizations in patients with heart failure 2.
• The efficacy of SGLT2 inhibitors in patients with heart failure and impaired renal function, such as those with anuria or oliguria, is not directly addressed in the provided studies.
• However, a study on ACE inhibitors in heart failure patients with impaired renal function suggests that neuro-hormonal antagonism, including SGLT2 inhibitors, may still be beneficial in these patients 3.
• Another study on SGLT2 inhibitors in patients with heart failure with reduced ejection fraction found that SGLT2 inhibitor use was associated with a 25% lower risk of all-cause mortality, but did not specifically address patients with anuria or oliguria 4.

Considerations for Patients with Anuria or Oliguria

• The use of SGLT2 inhibitors in patients with anuria or oliguria may require careful consideration of the potential benefits and risks, including the risk of worsening renal function.
• Close monitoring of renal function and serum potassium levels is recommended when using SGLT2 inhibitors in patients with heart failure, particularly those with impaired renal function 5, 3.
• Further research is needed to determine the safety and efficacy of SGLT2 inhibitors in patients with heart failure and anuria or oliguria.

Subgroup Analysis

• A systematic review and meta-analysis of SGLT2 inhibitors in patients with heart failure found that the composite of cardiovascular mortality or heart failure hospitalizations was significantly reduced with SGLT2 inhibitors across subgroups of sex, age, race, estimated glomerular filtration rate (eGFR), and New York Heart Association (NYHA) class 2.
• However, the study did not specifically analyze the subgroup of patients with anuria or oliguria.