Is Kerendia (finerenone) approved for the treatment of heart failure with preserved ejection fraction (HFpEF)?

Is Kerendia Approved for Heart Failure with Preserved Ejection Fraction?

Yes, finerenone (Kerendia) is now approved for heart failure with preserved ejection fraction (HFpEF) based on the FINEARTS-HF trial results, which demonstrated significant reduction in cardiovascular death and heart failure hospitalizations in patients with HFpEF and heart failure with mildly reduced ejection fraction (HFmrEF). 1

Current FDA Approval Status

• Finerenone was initially approved in the USA in 2021 to reduce the risk of sustained eGFR decline, end-stage renal disease, cardiovascular death, nonfatal myocardial infarction, and hospitalization for heart failure in adults with chronic kidney disease associated with type 2 diabetes 2
• The FINEARTS-HF trial (completed in 2024) enrolled 6,001 patients with heart failure and left ventricular ejection fraction ≥40%, demonstrating that finerenone was superior to placebo in reducing the primary composite outcome of total worsening heart failure events and cardiovascular death 1, 3

Evidence Supporting Use in HFpEF

FINEARTS-HF Trial Results

• In patients with HFpEF/HFmrEF (LVEF ≥40%), finerenone significantly reduced the composite endpoint of total (first and recurrent) worsening heart failure events and cardiovascular death compared to placebo 1
• The benefit was consistent regardless of background treatment with SGLT2 inhibitors, suggesting potential additive benefit with combination therapy 1
• Treatment benefit was maintained even in patients who developed hyperkalemia (potassium >5.5 mmol/L) with protocol-directed surveillance and dose adjustment 3

Real-World Evidence

• In a prospective real-world study of 31 patients with diabetic kidney disease (71% had HFpEF/HFmrEF), finerenone improved cardiac parameters including left atrial volume index, which decreased from 31.2 mL/m² at baseline to 26.6 mL/m² after 6 months (P=0.029) 4
• E/e' ratio (a marker of diastolic function) decreased from 11.9 at baseline to 9.9 after 6 months in the HFpEF/HFmrEF subgroup (P=0.043) 4

Important Context from Earlier Trials

• The FIGARO-DKD and FIDELIO-DKD trials in patients with chronic kidney disease and type 2 diabetes showed finerenone reduced heart failure hospitalizations by 29% (HR 0.71,95% CI 0.56-0.90) 5
• Critical exclusion criterion: These trials specifically excluded patients with heart failure with reduced ejection fraction and uncontrolled hypertension 5
• The pooled FIDELITY analysis (N=13,171) confirmed cardiovascular benefits across the spectrum of chronic kidney disease, with the exclusion of those with heart failure with reduced ejection fraction 5

Dosing and Safety Considerations

• Initial dosing: 10 mg once daily for patients with eGFR 25-60 mL/min/1.73 m², or 20 mg once daily for eGFR >60 mL/min/1.73 m² 5
• Dose escalation to 20 mg once daily is encouraged after 1 month if serum potassium ≤4.8 mmol/L and eGFR is stable 5
• Finerenone increased the risk of potassium >5.5 mmol/L (HR 2.16,95% CI 1.83-2.56) but decreased the risk of potassium <3.5 mmol/L (HR 0.46,95% CI 0.38-0.56) 3
• In real-world use, only 3.2% of patients had unplanned hospitalization with hyperkalemia up to 6.0 mmol/L 4

Clinical Positioning

Finerenone represents a new therapeutic option for HFpEF/HFmrEF, particularly valuable in patients with concomitant chronic kidney disease and type 2 diabetes. 1 The drug offers potent and selective mineralocorticoid receptor blockade with a more favorable side effect profile than spironolactone and eplerenone 1. Most patients in real-world studies were already on SGLT2 inhibitors (93.5%), suggesting finerenone can be safely added to contemporary guideline-directed medical therapy 4.

Common Pitfalls to Avoid

• Do not withhold finerenone solely due to mild hyperkalemia; clinical benefit was maintained even in patients whose potassium increased to >5.5 mmol/L with appropriate monitoring and dose adjustment 3
• Monitor serum potassium at 1 month and 3 months after initiation, as the increase in potassium is greatest during this period (median difference 0.19-0.23 mmol/L) 3
• Ensure baseline potassium ≤4.8 mmol/L before initiating therapy 5
• Monitor eGFR closely; expect a slight initial decrease (median drop from 52 to 48 mL/min/1.73 m² at 4 weeks) that stabilizes thereafter 4