What is the role of Finerenone (Mineralocorticoid Receptor Antagonist) in treating Heart Failure with Reduced Ejection Fraction (HFrEF)?

Finerenone for HFrEF: Limited Role Based on Current Evidence

Finerenone is NOT currently recommended for standard HFrEF treatment, as established guidelines prioritize traditional mineralocorticoid receptor antagonists (spironolactone and eplerenone) for this indication. 1 However, emerging evidence suggests finerenone may have a role in specific HFrEF populations, particularly those with concomitant type 2 diabetes and chronic kidney disease.

Current Guideline-Directed Therapy for HFrEF

The 2016 ESC guidelines establish the standard approach for HFrEF management:

• Spironolactone or eplerenone are the recommended MRAs for all symptomatic patients with HFrEF and LVEF ≤35% (despite treatment with ACE inhibitor and beta-blocker) to reduce mortality and heart failure hospitalization 1
• These traditional MRAs have Class I recommendation based on landmark trials (RALES, EPHESUS, EMPHASIS-HF) that demonstrated significant mortality reduction 1
• Finerenone is notably absent from established HFrEF treatment algorithms 1

Emerging Role: Specific Patient Populations

Type 2 Diabetes with CKD and Heart Failure

Finerenone should be considered in patients with type 2 diabetes, CKD with albuminuria, and heart failure (including HFrEF) who are already on maximum tolerated ACE inhibitor/ARB therapy:

• The 2024 ADA guidelines recommend finerenone for patients with type 2 diabetes and CKD with albuminuria, noting it reduces heart failure hospitalization by 29% (HR 0.71,95% CI 0.56-0.90) 1, 2
• Finerenone reduced composite cardiovascular outcomes (CV death, nonfatal MI, nonfatal stroke, or HF hospitalization) by 13% in the FIGARO-DKD trial 1
• A prespecified subgroup analysis revealed that in individuals without symptomatic HFrEF, finerenone reduces the risk for new-onset heart failure 1

Dosing and Initiation Criteria

For eligible patients with type 2 diabetes and CKD:

• Serum potassium must be <4.8 mmol/L before initiation 1, 3, 2
• eGFR must be ≥25 mL/min/1.73 m² 1, 3
• Start with 10 mg once daily if eGFR 25-60 mL/min/1.73 m², or 20 mg once daily if eGFR >60 mL/min/1.73 m² 1, 3, 2
• Uptitrate to 20 mg daily after 4 weeks if potassium remains <4.8 mmol/L 3

Therapeutic Positioning in HFrEF

The hierarchy for MRA selection in HFrEF is clear:

1. First-line: Spironolactone or eplerenone remain the standard MRAs for HFrEF 1
2. Consider finerenone: Only in the specific subset of HFrEF patients with type 2 diabetes and CKD with persistent albuminuria despite maximum tolerated RAS inhibition 3, 2
3. SGLT2 inhibitors are prioritized over finerenone for cardiorenal protection in diabetic patients with HFrEF 3
4. Combination therapy: Finerenone may be added to RAS inhibitor and SGLT2 inhibitor for complementary cardiorenal protection 3

Safety Monitoring: Critical Considerations

Hyperkalemia is the primary concern requiring vigilant monitoring:

• Hyperkalemia incidence: 10.8-14% with finerenone vs. 5.3-6.9% with placebo 1, 2
• Severe hyperkalemia requiring discontinuation occurs in only 1.2-1.7% of patients 1, 2
• Check potassium at baseline, after 4 weeks, then at 1,4,8, and 12 weeks after any dose adjustment 1, 3

Management of hyperkalemia:

• If potassium >5.5 mmol/L: withhold finerenone and restart at 10 mg daily when potassium ≤5.0 mmol/L 3
• Traditional guidelines recommend halving the MRA dose if potassium >5.5 mmol/L and stopping if >6.0 mmol/L 1

Common Pitfalls to Avoid

Do not substitute finerenone for spironolactone/eplerenone in standard HFrEF patients without the specific indication of concomitant type 2 diabetes and CKD with albuminuria 1, 3

Do not initiate finerenone if:

• Serum potassium is ≥4.8 mmol/L 1, 3
• eGFR is <25 mL/min/1.73 m² 1, 3
• Patient has impaired renal function without careful monitoring plans 1

Remember that adverse events in HFrEF trials are frequently observed (75-85% of patients) but occur at similar rates in placebo groups, suggesting many symptoms reflect the disease state rather than medication effects 1

Future Directions

Recent data from FINEARTS-HF (2024) demonstrated finerenone's efficacy in heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF), with a rate ratio of 0.84 for the composite outcome of cardiovascular death and total worsening HF events 4, 5. However, this evidence does not yet translate to guideline recommendations for standard HFrEF, where spironolactone and eplerenone remain the established MRAs of choice.