HFSA Studies Highlight Benefit of nsMRA vs Steroidal MRAs in Heart Failure Population

A pair of studies presented at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2025 are highlighting the potential advantages of finerenone (Kerendia) relative to traditional steroidal mineralocorticoid receptor agonists (MRAs) among patients with heart failure.

The propensity-matched studies, which both leveraged the TriNetX Global Collaborative Network as a data source, offer insight into the comparative effects in patients with heart failure with preserved ejection fraction (HFpEF) as well as a broader population of heart failure patients.1,2

Real-World Comparison of Cardiovascular Outcomes in HFpEF

Using data from the TriNetX network spanning January 2010 through March 2025, investigators conducted a retrospective cohort study to compare cardiovascular and renal outcomes among HFpEF patients treated with either finerenone or spironolactone, with a 3-year follow-up period. For the purpose of analysis, HFpEF was defined as an ejection fraction of 50% or greater.1

After propensity score matching, 1058 patients were included in each treatment group.1

Finerenone was associated with a markedly lower risk of all-cause mortality compared with spironolactone (RR, 0.35; 95% CI, 0.17–0.73; P = .003) and secondary outcomes consistently favored finerenone, including lower rates of hospitalization (RR, 0.67; 95% CI, 0.61–0.73; P <.001), heart failure exacerbation (RR, 0.77; 95% CI, 0.71–0.83; P <.001), new-onset acute kidney injury (RR, 0.67; 95% CI, 0.59–0.75; P <.001), and hyperkalemia (RR, 0.75; 95% CI, 0.62–0.92; P = .005).1

“In patients with HFpEF, finerenone was associated with a significant reduction in all-cause mortality, hospitalization, heart failure exacerbations, acute kidney injury, and hyperkalemia when compared to spironolactone,” wrote investigators, who were led by Mohammed Nor, MD, of Stamford Health.1

Clinical Outcomes in Heart Failure with nsMRA vs MRAs

Investigators used the TriNetX Global Collaborative Network to examine outcomes among adults diagnosed with heart failure between January 1, 2020, and December 31, 2023.

Patients were divided into 2 cohorts: those initiated on nonsteroidal MRAs (nsMRAs) and those receiving steroidal MRAs. Unlike the previous study, this analysis included patients using esaxerenone and eplerenone.2

Propensity score matching was performed across 36 variables, including demographics, comorbidities such as diabetes, chronic kidney disease, ischemic heart disease, cerebrovascular disease, hypertension, obesity, and obstructive sleep apnea, as well as concomitant cardiovascular therapies including beta-blockers, SGLT2 inhibitors, GLP-1 receptor agonists, diuretics, and RAAS agents.2

The sample population included 2224 individuals with heart failure using nsMRAs and 285,357 individuals with heart failure using steroidal MRAs. After matching, each cohort included 1910 patients.2

Treatment with nsMRAs was associated with significantly lower risk of several key outcomes compared with steroidal MRA therapy, including all-cause mortality (Risk ratio [RR], 0.38; 95% CI, 0.29–0.49), 3-point major adverse cardiovascular and cerebrovascular events (RR 0.52; 95% CI, 0.41–0.66), acute HF (RR 0.56; 95% CI, 0.40–0.78), cardiogenic shock (RR 0.39; 95% CI, 0.22–0.69), acute pulmonary edema (RR, 0.40; 95% CI, 0.23–0.69), respiratory failure (RR 0.55; 95% CI, 0.41–0.75), hyperkalemia (RR, 0.69; 95% CI, 0.53–0.90), and hypotension (RR 0.59; 95% CI, 0.46–0.77).2

Investigators pointed out there were no significant differences were observed for all-cause hospitalization, ICU admissions, end-stage heart failure, end-stage renal disease, or dialysis dependence.2

“The use of nonsteroidal MRAs in comparison to steroidal MRAs in individuals with HF was associated with a reduction in the risk for all-cause mortality, [3-point major adverse cardiovascular and cerebrovascular events], acute heart failure, acute pulmonary edema, respiratory failure, hyperkalemia, hypotension,” wrote investigators, who were led by Jai Sivanandan Nagarajan, MD, of Upstate Medical University.2 “Further research and more data like head-to-head clinical trials are needed to establish a clear advantage of nonsteroidal MRAs over steroidal MRAs.”

References:

1. Nor M. Comparing Spironolactone And Finerenone In Heart Failure With Preserved Ejection Fraction: A Real-world Cohort Study On Cardiovascular Outcomes. Presented at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2025. Minneapolis, MN. September 26-29, 2025.

2. Nagarajan J. Clinical Outcomes In Patients With Heart Failure Managed With Non-steroidal Vs Steroidal Mineralocorticoid Receptor Antagonists: A Propensity-score Matched Analysis. Presented at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2025. Minneapolis, MN. September 26-29, 2025.