Comparative Effectiveness of Finerenone Versus Spironolactone on Cardiovascular Outcomes in Heart Failure with Preserved Ejection Fraction: A Bayesian Network Meta-Analysis

Presenter: Abdul Haseeb Riaz

This systematic review and Bayesian network meta-analysis (PRISMA-NMA) included randomized and observational studies from major databases through September 2025, comparing finerenone and spironolactone versus placebo/no treatment. Outcomes included all-cause mortality, cardiovascular death, and hospitalization, analysed using Bayesian random-effects models with SUCRA ranking.

A total of 81,850 patients were analysed for all-cause mortality, 23,958 for cardiovascular death, and 30,365 for hospitalization. For all-cause mortality, both finerenone (OR 0.59, 95% CrI 0.20–1.68) and spironolactone (OR 0.66, 95% CrI 0.36–1.24) showed favourable trends, with finerenone ranking higher (SUCRA ~75–80%). For cardiovascular death, neither achieved significant reduction, though spironolactone ranked higher (SUCRA ~85%). For hospitalization, both showed benefit—finerenone (OR 0.79, 95% CrI 0.55–1.00) and spironolactone (OR 0.86, 95% CrI 0.71–0.999)—with finerenone ranking highest (SUCRA ~85%). Direct comparisons showed no significant differences between the two MRAs.

These findings suggest comparable efficacy between MRAs in HFpEF, with finerenone showing favourable ranking for mortality and hospitalization, and spironolactone for cardiovascular death.

Clinical Outcomes Among HFpEF Patients on Spironolactone vs Eplerenone: A Real-World Propensity Matched Analysis

Presenter: God-dowell O. Odukudu

Heart failure with preserved ejection fraction (HFpEF) remains challenging to manage, with limited comparative evidence among mineralocorticoid receptor antagonists. This retrospective cohort study from the TriNetX network compared eplerenone and spironolactone in HFpEF patients. After propensity score matching, 6,397 patients were included in each group, balanced for demographics, comorbidities, and medications. Outcomes assessed over a mean follow-up of 2.2 years included all-cause mortality, hospitalization, and cardiovascular events.

Eplerenone was associated with significantly improved outcomes compared to spironolactone, including lower all-cause mortality (21.2% vs 26.7%), hospitalization (38.5% vs 44.9%), progression to HFrEF (3.0% vs 4.3%), acute myocardial infarction (13.1% vs 14.9%), and heart failure exacerbation (34.6% vs 41.8%) (all p<0.01). Stroke rates were similar between groups.

These findings suggest that Eplerenone was associated with superior outcomes versus spironolactone in HFpEF, warranting confirmation in prospective trials.

Comparative Effectiveness and Safety of Spironolactone versus Eplerenone in Patients with HFrEF and Chronic Kidney Disease: A Real-World Propensity-Matched Analysis

Presenter: Abdulraheem Eniola Hassan

This retrospective cohort study compared outcomes between spironolactone and eplerenone in patients with heart failure with reduced ejection fraction (HFrEF) and coexisting chronic kidney disease (CKD). Adults with stage 3–5 CKD or ESRD were identified and propensity score matched (1:1), resulting in 1,182 patients in each group. Outcomes were assessed over 12 months.

Spironolactone was associated with a higher risk of hyperkalemia compared to eplerenone (12.7% vs 8.6%; RR 1.48; p=0.004). It was also linked to greater progression to end-stage heart failure (8.1% vs 5.2%; RR 1.54; p=0.013).

There were no significant differences between groups in all-cause mortality (17.9% vs 16.3%; HR 1.11; p=0.29), major adverse cardiovascular events (24.4% vs 23.1%; p=0.59), acute kidney injury, or ventricular arrhythmias. However, all-cause hospitalizations were modestly higher with spironolactone (46.0% vs 41.8%; HR 1.13; p=0.045).

These findings suggest that eplerenone is associated with lower risks of hyperkalemia, progression to advanced heart failure, and hospitalization compared to spironolactone, with similar mortality and cardiovascular outcomes.

Comparative Efficacy and Safety of Spironolactone, Eplerenone, Canrenone, and Finerenone in Heart Failure with Reduced Ejection Fraction: A Network Meta-Analysis of Randomized Trials

Presenter: Rakhshanda Khan

This network meta-analysis evaluated the comparative efficacy and safety of mineralocorticoid receptor antagonists (MRAs)—spironolactone, eplerenone, canrenone, and finerenone—in patients with heart failure with reduced ejection fraction (HFrEF).

A total of 34 RCTs including 22,632 patients were analysed. Eplerenone demonstrated superior outcomes compared to spironolactone in all-cause mortality (HR 0.78, 95% CI 0.66–0.91) and showed favourable trends in cardiovascular death and safety outcomes. Spironolactone significantly reduced cardiovascular death (HR 0.67, 95% CI 0.50–0.89), heart failure hospitalization (HR 0.61, 95% CI 0.43–0.86), all-cause hospitalization (HR 0.51, 95% CI 0.26–0.98), and cardiovascular hospitalization (HR 0.56, 95% CI 0.37–0.84).

Canrenone showed the strongest efficacy across all-cause mortality, composite outcomes, and heart failure hospitalization, although evidence was limited to fewer trials. Finerenone ranked as the safest agent, with lower risks of hyperkalemia (RR 1.56, 95% CI 0.89–2.74), renal injury (RR 0.56, 95% CI 0.24–1.29), overall adverse events (RR 0.84, 95% CI 0.75–0.94), and treatment discontinuation (RR 0.89, 95% CI 0.64–1.23).

Overall, MRAs were effective in HFrEF, with distinct efficacy and safety profiles, and a low overall risk of bias across included trials.

Safety of Mineralocorticoid Receptor Antagonists in Patients with Chronic Kidney Disease Stage 4-5: A Retrospective Review

Presenter: Deema Gichi

This single-center retrospective chart review aims to evaluate the safety of mineralocorticoid receptor antagonists (MRAs)—including spironolactone, eplerenone, and finerenone—in patients with advanced chronic kidney disease (CKD stage 4–5, eGFR <30 mL/min/1.73 m²) not receiving dialysis. Adult patients with indications such as heart failure, hypertension, hyperaldosteronism, or diabetic kidney disease treated between January 2021 and September 2024 are being included. The primary endpoint is the rate of hyperkalemia (serum potassium ≥5.3 mmol/L). Secondary endpoints include MRA dose reduction or discontinuation, hospitalizations due to hyperkalemia, and peak potassium levels.

Data collection is ongoing, with approximately 1,500 patient profiles expected to be reviewed. Results will be analyzed using descriptive statistics.

Overall, this study aims to provide real-world safety data on MRA use in advanced CKD.

ACC 2026, March 28 – 30, New Orleans, LA