What is the recommended use and dosage of Finrenone in clinical trials for patients with heart failure or diabetic kidney disease?

Finerenone in Clinical Trials for Heart Failure and Diabetic Kidney Disease

Finerenone is recommended for patients with type 2 diabetes and diabetic kidney disease at a dosage of 10-20 mg once daily to reduce the risk of progression from stage A heart failure to symptomatic incident heart failure, and to decrease cardiovascular events including hospitalization for heart failure. 1

Mechanism and Clinical Evidence

• Finerenone is a nonsteroidal mineralocorticoid receptor antagonist (MRA) with unique pharmacological properties offering potent and selective blockade of the mineralocorticoid receptor 2, 3
• Unlike steroidal MRAs (spironolactone and eplerenone), finerenone has demonstrated a more favorable side effect profile with less sexual side effects and no gynecomastia 2
• Two major clinical trials have established its efficacy:
  • FIDELIO-DKD: Evaluated finerenone versus placebo for kidney failure, sustained decrease of ≥40% in eGFR, or death from renal causes in patients with type 2 diabetes and diabetic kidney disease 1
  • FIGARO-DKD: Demonstrated that finerenone reduced the primary outcome of death from cardiovascular causes, nonfatal MI, nonfatal stroke, or hospitalization for heart failure (HR 0.87 [95% CI 0.76–0.98]; P = 0.03) 1, 4

Dosing Recommendations

• Starting dose: 10 mg once daily for patients with moderate CKD 1
• Target dose: 20 mg once daily if tolerated and no significant hyperkalemia develops 1, 2
• Dose adjustment based on serum potassium levels is necessary as hyperkalemia is a potential side effect 2

Patient Selection Criteria

• Primary candidates: Patients with type 2 diabetes and diabetic kidney disease 1
• Particularly beneficial for:
  • Patients with albuminuria (ACR ≥30 mg/g [≥3 mg/mmol]) 1
  • Patients with normal serum potassium (<4.8 mEq/l at screening) 1
  • Patients at risk for heart failure progression 1

Cardiovascular Benefits

• Reduces hospitalization for heart failure (HR 0.71 [95% CI 0.56–0.90]) 1
• Only 7.7-7.8% of study participants in the major trials had a prior history of heart failure, indicating finerenone's preventive effect against new-onset heart failure 1
• Reduces the composite outcome of death from cardiovascular causes, nonfatal MI, nonfatal stroke, or hospitalization for heart failure by 13% 1
• Recent evidence suggests potential benefits in patients with heart failure with mildly reduced or preserved ejection fraction 3

Renal Benefits

• Reduces kidney failure, sustained decrease in eGFR, and death from renal causes 1
• Reduces albuminuria and renal hypertrophy in preclinical models 5
• Complements SGLT2 inhibitors in kidney protection strategy 1

Safety Considerations and Monitoring

• Hyperkalemia is the most common significant adverse effect, requiring regular monitoring of serum potassium 2
• Hyperkalemia leading to drug withdrawal was significantly higher with finerenone compared to placebo 2
• No significant effects on HbA1c or body weight 2
• Only modest effects on blood pressure 2
• No sexual side effects including gynecomastia, unlike steroidal MRAs 2

Combination Therapy Considerations

• Can be used alongside SGLT2 inhibitors with potentially additive benefits 3
• Should be part of a comprehensive treatment approach that includes:
  • SGLT2 inhibitors (if eGFR ≥20 ml/min/1.73 m²) 1
  • RAS inhibitors at maximum tolerated dose (if hypertensive) 1
  • Metformin (if eGFR ≥30 ml/min/1.73 m²) 1

Ongoing Research

• FINEARTS-HF trial has shown that finerenone is superior to placebo in improving the composite outcome of total worsening heart failure events and death from cardiovascular causes in patients with heart failure and mildly reduced or preserved ejection fraction 3
• Additional research is investigating finerenone in non-diabetic CKD populations 5