Is finerenone indicated for heart failure with preserved ejection fraction?

Finerenone for Heart Failure with Preserved Ejection Fraction

Finerenone is now indicated for heart failure with preserved ejection fraction (HFpEF) and mildly reduced ejection fraction (HFmrEF), specifically for patients with LVEF ≥40%, based on the landmark FINEARTS-HF trial showing a 16% reduction in cardiovascular death and worsening heart failure events.

Current Evidence-Based Indication

The 2025 Canadian Cardiovascular Society/Canadian Heart Failure Society guidelines explicitly include finerenone as an evidence-based medication for heart failure with nonreduced ejection fraction (HFnrEF, which encompasses both HFpEF and HFmrEF with LVEF >40%) 1. This represents a major shift from previous guidance that limited finerenone recommendations to patients with diabetes and chronic kidney disease.

Key Trial Data

The FINEARTS-HF trial (2024) enrolled 6,001 patients with LVEF ≥40% and demonstrated that finerenone reduced the composite primary outcome of total worsening heart failure events and cardiovascular death (rate ratio 0.84,95% CI 0.74-0.95, P=0.007) 2. Critically, this benefit occurred regardless of whether patients had diabetes or CKD, expanding finerenone's indication beyond its original cardiorenal-metabolic niche 2, 3.

The benefit was primarily driven by an 18% reduction in total worsening heart failure events (rate ratio 0.82,95% CI 0.71-0.94, P=0.006), while cardiovascular death showed a non-significant trend toward reduction (HR 0.93,95% CI 0.78-1.11) 2.

Practical Implementation

Dosing Strategy

Starting dose: 10-20 mg once daily depending on baseline eGFR and potassium 1

• If eGFR 25-60 mL/min/1.73 m²: start 10 mg daily
• If eGFR ≥60 mL/min/1.73 m²: start 20 mg daily

Target dose: 20-40 mg once daily 1

• Uptitrate after 4 weeks if potassium ≤4.8 mmol/L and eGFR stable

Patient Selection Criteria

Finerenone should be prescribed for:

• Confirmed symptomatic HF with LVEF ≥40%
• New York Heart Association class II-IV symptoms
• Elevated natriuretic peptides (NT-proBNP >300 pg/mL or BNP >100 pg/mL, or if hospitalized for HF within 12 months, NT-proBNP >600 pg/mL)
• Baseline potassium ≤5.0 mmol/L
• eGFR ≥25 mL/min/1.73 m²

Critical Exclusions

Do not prescribe finerenone if:

• Current hyperkalemia (K+ >5.0 mmol/L)
• eGFR <25 mL/min/1.73 m²
• Concomitant use of strong CYP3A4 inhibitors
• Addison's disease or other conditions causing hyperkalemia

Positioning in Treatment Algorithm

The 2025 Canadian guidelines position finerenone as a Tier 1 therapy alongside SGLT2 inhibitors for HFnrEF 1. This represents the highest level of recommendation, indicating it should be initiated early in the treatment course, not reserved as add-on therapy.

Combination with SGLT2 Inhibitors

Finerenone and SGLT2 inhibitors should be used together, not as alternatives 1, 4. The FINEARTS-HF trial showed consistent benefits regardless of baseline SGLT2 inhibitor use, and the mechanisms are complementary:

• SGLT2 inhibitors: osmotic diuresis, metabolic effects, reduced preload/afterload
• Finerenone: anti-inflammatory, anti-fibrotic, reduced cardiac remodeling

Comparison to Steroidal MRAs

While spironolactone has shown modest benefits in HFpEF (TOPCAT trial), finerenone offers several advantages:

• More selective mineralocorticoid receptor antagonism with less hormonal side effects (gynecomastia, menstrual irregularities) 3, 5
• Equal distribution between heart and kidney tissue versus predominantly renal effects of spironolactone 5
• Lower hyperkalemia risk in clinical trials 2, 5

A recent real-world comparison showed similar effectiveness but potentially lower mortality with finerenone versus spironolactone (4.4% vs 8.0%, HR 0.48,95% CI 0.23-1.00), though this requires confirmation in prospective trials 6.

Diabetes and CKD Context

For patients with type 2 diabetes and CKD, finerenone remains strongly recommended based on the FIDELIO-DKD and FIGARO-DKD trials, which showed:

• 13-14% reduction in cardiovascular death, MI, stroke, or HF hospitalization 7, 8
• 23% reduction in kidney failure or sustained eGFR decline 9, 10
• Benefits for preventing progression from stage A (at-risk) to symptomatic heart failure 7, 8

The 2025 ADA Standards of Care explicitly state: "treatment with finerenone is recommended in people with type 2 diabetes and CKD to reduce the risk of progression from stage A heart failure to symptomatic incident heart failure" 8.

Safety Monitoring Protocol

Baseline Assessment

• Serum potassium and eGFR
• Confirm absence of acute decompensated HF requiring IV diuretics
• Review medication list for CYP3A4 inhibitors and potassium-sparing agents

Follow-up Monitoring

• Recheck potassium and eGFR at 4 weeks after initiation or dose change 4
• If K+ 5.1-5.4 mmol/L: reduce dose by 50%
• If K+ 5.5-5.9 mmol/L: hold dose, recheck in 3-7 days
• If K+ ≥6.0 mmol/L: discontinue permanently

Hyperkalemia Management

In FINEARTS-HF, hyperkalemia occurred more frequently with finerenone but was manageable 2. The incidence of treatment discontinuation due to hyperkalemia was low when proper monitoring protocols were followed 9, 10.

Practical tip: Patients with eGFR 25-45 mL/min/1.73 m² require more intensive monitoring, with potassium checks every 2-4 weeks during titration 4.

Common Clinical Pitfalls

1. Waiting for "optimal" SGLT2 inhibitor therapy before starting finerenone - Both should be initiated early and can be started simultaneously 1, 4

2. Avoiding finerenone in patients without diabetes or CKD - FINEARTS-HF showed benefits across all subgroups, including those without cardiorenal-metabolic comorbidities 2, 3

3. Using steroidal MRAs interchangeably with finerenone - While both are MRAs, finerenone has distinct pharmacology and a more favorable side effect profile for HFpEF 3, 5

4. Inadequate potassium monitoring - The 4-week recheck is critical; many hyperkalemia events are preventable with proper surveillance 4

5. Confusing HFpEF with HFpEF mimics - Ensure true HFpEF diagnosis by excluding cardiac amyloidosis, hypertrophic cardiomyopathy, constrictive pericarditis, and high-output states before initiating therapy 11

Evidence Strength and Limitations

The recommendation for finerenone in HFpEF is based on one large, well-designed randomized controlled trial (FINEARTS-HF) with 6,001 patients and median 32-month follow-up 2. While this represents high-quality evidence, it is newer than the extensive SGLT2 inhibitor data. The cardiovascular mortality benefit was not statistically significant as an individual endpoint, with the primary benefit being reduction in heart failure hospitalizations 2, 12.

The evidence is strongest for: Symptomatic patients with LVEF ≥40%, elevated natriuretic peptides, and adequate renal function who can tolerate potassium monitoring 2, 4.