Finerenone is a novel nonsteroidal mineralocorticoid-receptor antagonist (MRA) that reduces adverse cardiovascular and renal outcomes in patients with chronic kidney disease and diabetes. Its comparative effectiveness against steroidal MRAs in cardio-oncology patients with higher clinical burden remains unknown. We aim to evaluate whether finerenone use in cardio-oncology patients is associated with reduced heart failure admissions and hyperkalemia events compared with spironolactone over 1 year. Secondary exploratory outcomes were also analyzed. We conducted a retrospective observational analysis using the TriNetX database comprising adults with a history of cancer, heart failure with a baseline ejection fraction ≥40%, and MRA initiation. Cardiovascular and renal outcomes were compared over 1 year of drug initiation after 1:1 propensity matching using Cox proportional hazard ratios (HRs). A total of 872 matched patients were included (mean age = 72, 45% female, 50% white, 23% receiving chemotherapy, 69% chronic kidney disease, and 90% diabetes). Finerenone users were associated with a lower risk of heart failure exacerbation (HR 0.51; 95% CI 0.35–0.76), all-cause mortality (HR 0.41; 95% CI 0.21–0.80), severe hyperkalemia (HR 0.57; 95% CI 0.40–0.83), and renal failure (HR 0.71; 95% CI 0.54–0.93) compared to spironolactone over 1 year. Individual risk of stroke was not different; however, composite major adverse cardiac events was lower with finerenone (HR 0.67; 95% CI 0.51–0.88), driven primarily by fewer heart failure events. In conclusion, finerenone was associated with fewer cardiac and renal adverse events with lower observed mortality compared with spironolactone in patients with a cancer history and heart failure (left ventricular ejection fraction ≥40%).
Highlights
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Finerenone is associated with reduced HF events and hyperkalemia compared to spironolactone in a cardio-oncology cohort.
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Fewer 1-year mortalities were observed among finerenone users.
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Finerenone is associated with lower major adverse cardiac events, driven by fewer HF events.
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Cardiac and renal advantages likely stem from nonsteroidal mineralocorticoid-receptor antagonist properties.
Clinical Perspectives
What Is New?
In heart failure patients with a left ventricular ejection fraction ≥40% and concomitant cancer history, finerenone was associated with a lower risk of heart failure exacerbations, severe hyperkalemia, all-cause mortality, hospitalizations, acute kidney injury, composite major adverse cardiac events, and myocardial infarction compared to similar users on spironolactone. These patient-centered clinical benefits are likely attributed to greater cardiac selectivity and potent anti-fibrotic effects on cardiac tissue than older steroidal MRAs.
What Are the Clinical Implications?
Future studies should further delineate patient subgroups that may preferentially benefit from finerenone over spironolactone, as demonstrated in cardio-oncology populations. This large, multi-institutional, propensity-matched analysis provides a rationale for randomized prospective trials comparing finerenone with other MRAs to demonstrate causality and further support guidance in clinical practice.
Mineralocorticoid antagonists (MRAs) reduce mortality and heart failure hospitalizations in patients with reduced ejection fraction, and current guidelines also suggest they may be utilized for heart failure with preserved ejection fraction (HFpEF). ,, However, these agents pose risks, including hyperkalemia and acute renal failure. Patients with a concomitant cancer history have a higher disease burden that makes them vulnerable to these associated health risks. ,,, Finerenone is a novel nonsteroidal mineralocorticoid-receptor antagonist (MRA) recently approved in 2021 that demonstrated a reduction in cardiovascular and renal outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes. Subsequent phase III demonstrated reductions in heart failure events in patients with CKD and diabetes. Direct comparisons between finerenone and spironolactone have demonstrated lower rates of severe hyperkalemia and less decline in kidney function. ,
Patients with heart failure and a history of cancer are a particularly vulnerable population. Advances in cancer therapy have improved survival but have increased the burden of comorbidities, including HFpEF, hypertension, diabetes, and renal dysfunction in a rapidly growing survivorship population. Treatments such as anthracyclines, HER2 inhibitors, and radiation contribute toward increased myocardial fibrosis and adverse remodeling pathways that are also modulated by mineralocorticoid receptors. ,,,, Finerenone may offer a potential advance in therapy, especially in cardio-oncology patients, due to its favorable safety profile and potent anti-fibrotic effects.
Despite an expanding role of finerenone within guideline-directed medical therapy (GDMT), comparative data between finerenone and spironolactone in patients with heart failure with concomitant cancer history are lacking. We therefore utilize a large, collaborative electronic health record (EHR) database to evaluate the association of finerenone versus spironolactone on heart failure exacerbation and significant hyperkalemia as primary endpoints. Secondary outcomes included composite major adverse cardiac events (MACE), all-cause mortality, all-cause hospitalization, acute renal failure, ventricular arrhythmias, and new onset atrial fibrillation.
Methods
Data source
A retrospective observational cohort study was performed using the TrinetX collaborative research network between January 2021 and January 2025. The TrinetX research network is a global shared database comprising approximately 110 million patients from diverse US health care institutions. This network provides aggregate, deidentified data per the deidentification standards defined in section §164.514(a) of the Health Insurance Portability and Accountability Act Privacy Rule. Because this study used deidentified aggregate data, it was determined to be exempt by the Institutional Review Board of the University of Maryland.
Patient population
Inclusion criteria for the patient population included adults aged >18 years who have a concomitant history of heart failure and malignant neoplasm using International Classification of Diseases-10th Revision (ICD-10) codes. Patients were grouped into cohorts if there was evidence of a first-time finerenone or spironolactone prescription after the first incidence of accumulating diagnoses of heart failure and cancer using ICD codes, RxNorm codes, and compiled EHR data. Patients with any history of malignant neoplasm identified using ICD-10 codes C00-D49, including those with active and prior cancer before the first MRA prescription, were included to approximate a real-world cardio-oncology population. Patients were only included if they were new users and had documented evidence of multiple instances of prescriptions. Patients with hospitalization or heart failure exacerbation within one month of first MRA prescription were excluded to mitigate bias from patients who may already be acutely ill at the index date. Detailed inclusion and exclusion criteria are detailed in Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) ( Figure 1 ). The supplemental appendix contains the specific Current Procedural Terminology and ICD-10 codes that were used for cohort screening and study window definitions.
STROBE figure. Diagram illustrating inclusion and exclusion criteria for the patient population and development of cohorts prior to comparative analysis.
Study endpoints
Patients were followed from the index date, defined as the first recorded prescription of finerenone or spironolactone, among those with heart failure with left ventricular ejection fraction (LVEF) ≥40% and a history of malignant neoplasm. Patients were followed for a twelve-month period, and clinical outcomes were recorded. A 12-month follow-up period was selected to ensure ample exposure to the drug and to adjust for median follow-up time to reduce any immortality bias. The primary outcomes were incidence of acute on chronic heart failure and evidence of severe hyperkalemia, defined as having an ICD-10 code of acute on chronic heart failure (I50.23, I50.33) or serum potassium >5.5, respectively. Secondary endpoints included MACE, acute myocardial infarction, stroke, all-cause mortality, acute renal failure, new onset atrial fibrillation or flutter, and any ventricular arrhythmia. Further details on outcome definitions are included in the supplemental index, which highlights specific database inputs.
Statistical analysis
Baseline characteristics were compared between finerenone and spironolactone cohorts using Student’s t tests for continuous variables and chi-square tests for categorical variables. Propensity analysis using 1:1 matching using a greedy nearest-neighbor algorithm without replacement and a caliper of 0.1 standard deviations of the propensity score was performed. Categorical and binary covariates, as detailed in Table 1 , were included to reduce confounding factors toward the cardiovascular and general clinical outcomes of interest. Cohort sizes before and after matching are reported in the STROBE diagram ( Figure 1 ). Time-to-event outcomes were compared using Kaplan–Meier curves and log-rank tests. Hazard ratios (HRs) were estimated using Cox proportional hazard models, censoring for death among nonfatal endpoints with robust standard errors to account for matching.
Table 1
Baseline characteristics and propensity matching
| Characteristic name | Category | Finerenone cohort before: patient count | Spironolactone cohort before: patient count | Before: standardized mean difference | Finerenone cohort after: patient count | Spironolactone cohort after: patient count | After: standardized mean difference |
|---|---|---|---|---|---|---|---|
| Demographics | |||||||
| Age at Index | 459 | 63,465 | 0.11 | 436 | 436 | 0.03 | |
| Male | 260 | 29,905 | 0.19 | 241 | 243 | 0.01 | |
| White | 222 | 45,250 | 0.48 | 222 | 212 | 0.05 | |
| Female | 199 | 33,532 | 0.19 | 195 | 192 | 0.01 | |
| Black or African American | 84 | 11,095 | 0.02 | 84 | 83 | 0.01 | |
| Asian | 90 | 2,180 | 0.52 | 71 | 72 | 0.01 | |
| Lab Values | |||||||
| Glomerular filtration rate | 0-30 mL/min/{1.73 m 2 } | 225 | 11,955 | 0.67 | 204 | 195 | 0.04 |
| Glomerular filtration rate | 30-60 mL/min/{1.73 m 2 } | 401 | 39,131 | 0.62 | 379 | 386 | 0.05 |
| Glomerular filtration rate | At least 60 mL/min/{1.73 m 2 } | 357 | 51,809 | 0.10 | 341 | 337 | 0.02 |
| Potassium | 432 | 56,909 | 0.45 | 409 | 408 | 0.38 | |
| Potassium | At most 5 mmol/L | 432 | 56,799 | 0.17 | 409 | 407 | 0.02 |
| Potassium | 5–5.5 mmol/L | 259 | 21,262 | 0.47 | 244 | 231 | 0.06 |
| Potassium | 5.5–100 mmol/L | 143 | 8,573 | 0.43 | 131 | 139 | 0.04 |
| Natriuretic peptide B | 213 | 24,294 | 0.22 | 202 | 201 | 0.09 | |
| Natriuretic peptide B | 0–1,000 pg/mL | 208 | 22,735 | 0.19 | 197 | 195 | 0.01 |
| Natriuretic peptide B | 1,000–5,000 pg/mL | 21 | 4,162 | 0.09 | 20 | 24 | 0.04 |
| Natriuretic peptide B | At least 5,000 pg/mL | 0 | 310 | 0.10 | 0 | 0 | |
| Troponin I.cardiac | 131 | 17,079 | 0.01 | 123 | 132 | 0.00 | |
| Troponin I.cardiac | 0–0.001 ng/mL | 25 | 4,388 | 0.06 | 25 | 28 | 0.03 |
| Troponin I.cardiac | 0.001–0.014 ng/mL | 47 | 5,793 | 0.04 | 44 | 45 | 0.01 |
| Troponin I.cardiac | 0.014–0.042 ng/mL | 75 | 8,971 | 0.06 | 70 | 75 | 0.03 |
| Troponin I.cardiac | 0.042–0.14 ng/mL | 40 | 5,821 | 0.02 | 39 | 35 | 0.03 |
| Troponin I.cardiac | At least 0.14 ng/mL | 42 | 5,017 | 0.04 | 37 | 36 | 0.01 |
| Left ventricular ejection fraction (LVEF) (%) | 47 | 8,421 | 0.29 | 47 | 34 | 0.01 | |
| Left ventricular ejection fraction (LVEF) (%) | 0%–39% | 0 | 0 | 0 | 0 | ||
| Left ventricular ejection fraction (LVEF) (%) | 40%–50% | 10 | 2,214 | 0.08 | 10 | 10 | 0.00 |
| Left ventricular ejection fraction (LVEF) (%) | 50%–100% | 44 | 7,608 | 0.08 | 44 | 32 | 0.10 |
| Conditions | |||||||
| BMI | 374 | 48,479 | 0.03 | 352 | 354 | 0.08 | |
| BMI | 0–18 kg/m 2 | 37 | 3,298 | 0.12 | 34 | 36 | 0.02 |
| BMI | 18–25 kg/m 2 | 133 | 16,105 | 0.08 | 123 | 123 | 0.00 |
| BMI | 25–30 kg/m 2 | 227 | 25,886 | 0.17 | 209 | 204 | 0.02 |
| BMI | 30–40 kg/m 2 | 263 | 30,203 | 0.20 | 249 | 238 | 0.05 |
| BMI | At least 40 kg/m 2 | 116 | 13,663 | 0.09 | 114 | 122 | 0.04 |
| ECOG Performance status | 10 | 61 | 0.12 | 10 | 10 | 0.00 | |
| ECOG Performance status | 0–1 {score} | 10 | 54 | 0.20 | 10 | 10 | 0.00 |
| ECOG Performance Status | 1–2 {score} | 10 | 48 | 0.20 | 10 | 10 | 0.00 |
| ECOG Performance Status | 2–3 {score} | 10 | 28 | 0.20 | 10 | 10 | 0.00 |
| ECOG Performance Status | 3–4 {score} | 0 | 10 | 0.02 | 0 | 10 | 0.22 |
| ECOG Performance Status | 4–5 {score} | 0 | 10 | 0.02 | 0 | 0 | |
| Essential (primary) hypertension | 444 | 54,518 | 0.39 | 422 | 421 | 0.01 | |
| Diabetes mellitus | 417 | 29,092 | 1.11 | 394 | 392 | 0.02 | |
| Hyperlipidemia, unspecified | 408 | 42,988 | 0.53 | 388 | 398 | 0.08 | |
| Chronic kidney disease, stage 3 (moderate) | 323 | 13,468 | 1.13 | 301 | 298 | 0.01 | |
| Atherosclerotic heart disease of the native coronary artery without angina pectoris | 311 | 32,920 | 0.33 | 295 | 305 | 0.05 | |
| Personal history of nicotine dependence | 189 | 21,607 | 0.15 | 175 | 185 | 0.05 | |
| Atrial fibrillation and flutter | 172 | 26,415 | 0.08 | 168 | 157 | 0.05 | |
| Other chronic obstructive pulmonary disease | 150 | 17,558 | 0.11 | 142 | 137 | 0.02 | |
| Other peripheral vascular diseases | 123 | 10,340 | 0.26 | 115 | 125 | 0.05 | |
| Old myocardial infarction | 107 | 11,392 | 0.13 | 101 | 104 | 0.02 | |
| Chronic kidney disease, stage 4 (severe) | 114 | 2,825 | 0.60 | 99 | 86 | 0.07 | |
| Acute myocardial infarction | 90 | 11,041 | 0.06 | 86 | 102 | 0.09 | |
| Cerebral infarction | 73 | 7,013 | 0.14 | 69 | 75 | 0.04 | |
| Acute on chronic diastolic (congestive) heart failure | 68 | 7,018 | 0.11 | 67 | 67 | 0.00 | |
| Ventricular tachycardia | 39 | 6,792 | 0.07 | 37 | 30 | 0.06 | |
| Acute on chronic systolic (congestive) heart failure | 30 | 5,073 | 0.06 | 30 | 29 | 0.01 | |
| Ventricular tachycardia, unspecified | 22 | 2,827 | 0.02 | 20 | 20 | 0.00 | |
| Chronic kidney disease, stage 5 | 20 | 759 | 0.19 | 18 | 16 | 0.02 | |
| Ventricular fibrillation and flutter | 10 | 1,026 | 0.04 | 10 | 10 | 0.00 | |
| Ventricular fibrillation | 10 | 953 | 0.05 | 10 | 10 | 0.00 | |
| Ventricular flutter | 0 | 97 | 0.06 | 0 | 0 | ||
| Medications | |||||||
| Beta Blockers/Related | 418 | 49,988 | 0.35 | 396 | 398 | 0.02 | |
| Loop Diuretics | 348 | 44,171 | 0.14 | 338 | 348 | 0.06 | |
| Atorvastatin | 326 | 30,523 | 0.48 | 307 | 312 | 0.03 | |
| Sodium-glucose co-transporter 2 (SGLT2) inhibitors | 326 | 8,165 | 1.46 | 303 | 307 | 0.02 | |
| ANGIOTENSIN II INHIBITOR | 305 | 28,100 | 0.46 | 286 | 289 | 0.01 | |
| ACE INHIBITORS | 226 | 30,243 | 0.03 | 222 | 226 | 0.02 | |
| Rosuvastatin | 149 | 9,456 | 0.42 | 142 | 137 | 0.02 | |
| Anthracyclines and related substances | 10 | 986 | 0.05 | 10 | 10 | 0.00 | |
| Chemotherapy | 101 | 13,990 | 0.00 | 93 | 103 | 0.05 | |
| Radiation | 17 | 3,576 | 0.09 | 15 | 19 | 0.05 | |
| Visit: Inpatient Encounter | 342 | 35,950 | 0.38 | 321 | 328 | 0.04 | |
| Visit: Inpatient Acute | 22 | 743 | 0.21 | 18 | 21 | 0.03 | |
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