What is the role of finerenone in the treatment of a patient with heart failure (HF) and mildly reduced ejection fraction (EF), particularly those with a history of diabetes or kidney disease?

Finerenone for Heart Failure with Mildly Reduced Ejection Fraction

Finerenone is now an evidence-based treatment option for patients with HF and mildly reduced EF (HFmrEF), particularly those with concomitant diabetes and chronic kidney disease, based on recent trial data showing significant reductions in heart failure hospitalizations and cardiovascular events. 1, 2

Primary Indication and Patient Selection

For patients with HFmrEF who also have type 2 diabetes and CKD (eGFR ≥25 mL/min/1.73 m² with albuminuria UACR ≥30 mg/g), finerenone should be strongly considered as it reduces cardiovascular death or heart failure hospitalization by 14% and heart failure hospitalizations specifically by 29%. 1, 3

Key Patient Characteristics for Finerenone Use:

• Type 2 diabetes with CKD (eGFR 25-90 mL/min/1.73 m²) and persistent albuminuria (UACR ≥30 mg/g) despite maximum tolerated RAS blockade 3
• HFmrEF or HFpEF with or without diabetes, based on FINEARTS-HF trial results showing benefit across the entire LVEF spectrum 2, 4
• Normal baseline potassium (<4.8 mEq/L at screening) 5
• Exclude patients with symptomatic HFrEF, as the pivotal trials excluded this population and steroidal MRAs remain the standard 6, 1

Dosing Algorithm

Start with eGFR-based dosing:

• eGFR 25-60 mL/min/1.73 m²: Start 10 mg once daily 1, 3
• eGFR >60 mL/min/1.73 m²: Start 20 mg once daily 1, 3

Titrate to target dose of 20 mg once daily if tolerated and no significant hyperkalemia develops after 4 weeks. 5

Clinical Benefits Across Multiple Outcomes

Cardiovascular Protection:

• 13-14% reduction in composite cardiovascular death, MI, stroke, and heart failure hospitalization (HR 0.86-0.87) 6, 1, 3
• 29% reduction in heart failure hospitalizations (HR 0.71), which drives the primary benefit 1, 3
• Benefit evident early in treatment and sustained across follow-up 4

Renal Protection:

• 23% reduction in composite kidney outcomes (sustained ≥57% decrease in eGFR or renal death) 1, 3
• 36% reduction in end-stage kidney disease (HR 0.64) 1, 3
• Benefits observed across wide range of baseline kidney function (eGFR 25-90 mL/min/1.73 m²) 1

Real-World Cardiac Effects in HFmrEF/HFpEF:

• Reduction in left atrial volume index from 31.2 to 26.6 mL/m² over 6 months 7
• Improvement in E/e' ratio from 11.9 to 9.9 in patients with HFpEF/HFmrEF, indicating improved diastolic function 7
• Stable NT-proBNP and left ventricular mass index during treatment 7

Critical Monitoring and Safety

Hyperkalemia Management:

Hyperkalemia occurs in 10.8% of patients versus 5.3% with placebo, but only 1.2% discontinue due to hyperkalemia. 6, 3

Monitoring schedule:

• Check potassium at baseline, 4 weeks after initiation, and regularly throughout treatment 3
• Expect slight initial increase in potassium (median 4.2 to 4.4 mmol/L at 4 weeks) that stabilizes thereafter 7
• Expect slight initial decrease in eGFR (median 52 to 48 mL/min/1.73 m² at 4 weeks) that stabilizes thereafter 7

Common Pitfalls to Avoid:

• Do not withhold finerenone solely due to fear of hyperkalemia—the risk is manageable with proper monitoring and dose adjustments 3
• Do not assume lack of benefit in patients already on ACE inhibitors or ARBs—finerenone provides additional benefit beyond RAS blockade, though caution with potassium monitoring is warranted 1, 5
• Do not exclude patients with HFmrEF/HFpEF who lack diabetes—FINEARTS-HF demonstrated benefit regardless of diabetes status 2, 4

Combination Therapy Strategy

Finerenone can and should be used alongside SGLT2 inhibitors for complementary cardiorenal protection with potentially additive benefits. 5, 3, 2

Optimal Treatment Sequence:

• First-line: Maximize RAS inhibitor (ACE inhibitor or ARB) and add SGLT2 inhibitor 5, 3
• Second-line: Add finerenone for patients with persistent albuminuria despite first-line therapy 3
• The benefit of finerenone is consistent regardless of background SGLT2 inhibitor use, suggesting true additive effect 2, 4

Evidence Strength and Context

The evidence for finerenone in HFmrEF is now robust, with the FINEARTS-HF trial (2025) demonstrating superiority over placebo in reducing total worsening HF events and cardiovascular death across the entire LVEF spectrum. 2, 4 This complements earlier data from FIGARO-DKD and FIDELIO-DKD trials that established benefit in diabetic kidney disease populations. 6, 8

Important distinction: The original FIGARO-DKD and FIDELIO-DKD trials excluded patients with symptomatic HFrEF, so evidence is strongest for HFpEF and HFmrEF populations. 1 For HFrEF, steroidal MRAs (spironolactone, eplerenone) remain the guideline-recommended agents with Class I evidence. 9

When to Refer to Nephrology

Consider nephrology referral when eGFR <30 mL/min/1.73 m² for management of advanced kidney disease and discussion of renal replacement therapy. 6, 1 Also refer for continuously rising UACR, continuously declining eGFR, difficult management issues (resistant hyperkalemia, resistant hypertension), or uncertainty about kidney disease etiology. 6