What is the role of finerenone in treating heart failure, particularly in patients with chronic kidney disease or at risk of hyperkalemia?

Role of Finerenone in Heart Failure, Particularly in Patients with CKD or at Risk of Hyperkalemia

Finerenone significantly reduces heart failure hospitalizations and cardiovascular events in patients with chronic kidney disease and type 2 diabetes, and has recently demonstrated efficacy in heart failure with mildly reduced or preserved ejection fraction, making it an important therapeutic option despite the increased risk of hyperkalemia. 1, 2

Efficacy in Heart Failure and CKD

• Finerenone, a nonsteroidal mineralocorticoid receptor antagonist (MRA), shows significant cardiovascular benefits in patients with chronic kidney disease and type 2 diabetes, with a 13% reduction in primary cardiovascular endpoints (cardiovascular death, myocardial infarction, stroke, and heart failure hospitalization) 1
• The benefit is primarily driven by a 29% reduction in heart failure hospitalizations (HR 0.71 [95% CI 0.56–0.90]) 1
• In the FINEARTS-HF trial, finerenone demonstrated efficacy in heart failure with mildly reduced or preserved ejection fraction (HFpEF), reducing total worsening heart failure events by 18% compared to placebo (rate ratio 0.82; 95% CI 0.71-0.94) 2
• The FIDELITY pooled analysis (combining FIGARO-DKD and FIDELIO-DKD trials) showed a 14% reduction in composite cardiovascular outcomes across the spectrum of CKD severity 1

Renal Benefits

• Finerenone provides significant renal protection with a 23% reduction in composite kidney outcomes (sustained ≥57% decrease in eGFR or renal death) 1
• Notable 36% reduction in end-stage kidney disease was observed in the FIGARO-DKD trial (HR 0.64 [95% CI 0.41–0.995]) 1
• Benefits are observed across a wide range of baseline kidney function (eGFR 25-90 mL/min/1.73 m²) 1

Hyperkalemia Management

• Finerenone is associated with increased risk of hyperkalemia (10.8% vs 5.3% with placebo), but treatment discontinuation due to hyperkalemia is relatively low (1.2% in FIGARO-DKD) 1
• In FINEARTS-HF, despite increased hyperkalemia risk (HR 2.16 [95% CI 1.83-2.56]), clinical benefits were maintained even in patients whose potassium levels increased to >5.5 mmol/L 3
• Protocol-directed surveillance and dose adjustment are essential to manage hyperkalemia risk while maintaining clinical benefits 3

Dosing and Monitoring

• For patients with eGFR 25-60 mL/min/1.73 m², start with 10 mg once daily 1
• For patients with eGFR >60 mL/min/1.73 m², start with 20 mg once daily 1
• Dose uptitration from 10 mg to 20 mg should be considered after 1 month if serum potassium is ≤4.8 mmol/L and eGFR is stable 1
• Regular monitoring of serum potassium is essential, especially in patients with reduced kidney function 3

Advantages Over Traditional MRAs

• Finerenone has higher selectivity toward the mineralocorticoid receptor compared to spironolactone and stronger binding affinity than eplerenone 4
• As a nonsteroidal MRA, finerenone avoids the endocrine side effects (gynecomastia, hirsutism) associated with spironolactone 4, 5
• Finerenone reduces the risk of hypokalemia (HR 0.46 [95% CI 0.38-0.56]) while increasing risk of hyperkalemia, providing a more balanced electrolyte profile 3

Patient Selection and Considerations

• Finerenone is particularly beneficial for patients with type 2 diabetes and CKD with elevated urinary albumin-to-creatinine ratio (UACR ≥30 mg/g) and eGFR 25-90 mL/min/1.73 m² 1
• Benefits are consistent regardless of baseline HbA1c levels or insulin use 6
• Patients with heart failure with reduced ejection fraction (HFrEF) were excluded from the FIGARO-DKD trial, so evidence is stronger for HFpEF 1
• Consider nephrology referral when eGFR <30 mL/min/1.73 m² for management of advanced kidney disease 1

Combination with Other Therapies

• Finerenone can be used alongside SGLT2 inhibitors for complementary cardiorenal protection (4.5% of patients in FIDELIO-DKD were on SGLT2 inhibitors) 1
• There have been no direct comparison studies between MRAs, SGLT2 inhibitors, and GLP-1 receptor agonists, so clinical judgment is needed when deciding which to prescribe initially or in combination 1
• Finerenone should be used with caution in patients already on ACE inhibitors or ARBs due to increased hyperkalemia risk 1