Nonsteroidal mineralocorticoid receptor antagonists (MRAs), such as finerenone, were developed to possess pharmacologic properties distinct from those of traditional steroidal MRAs such as spironolactone. Recent clinical trials have demonstrated that finerenone reduces the risk of kidney disease progression and cardiovascular events in patients with chronic kidney disease and type 2 diabetes. Furthermore, in the FINEARTS-HF trial, finerenone significantly lowered the rate of a composite endpoint of total worsening heart failure events and cardiovascular death in patients with heart failure with mildly reduced or preserved ejection fraction (EF), compared with placebo. These findings suggest that finerenone may provide therapeutic benefit across a broader spectrum of heart failure phenotypes.
Patients with active cancer or a history of cancer are well known to have a higher risk of developing heart failure than those without cancer. Among patients with cancer, heart failure commonly results from cancer therapy–related cardiac dysfunction (CTRCD), which is frequently induced by cardiotoxic agents such as anthracyclines and certain molecularly targeted therapies, including HER2 inhibitors. Although guideline-directed medical therapy remains the foundation of heart failure management in both cancer and noncancer populations, treatment in patients with active cancer is often more complex with respect to both efficacy and safety. In addition, discontinuation of cancer therapy may adversely affect overall prognosis. Steroidal MRAs are class I guideline-recommended medications for heart failure with reduced EF (HFrEF), but not for heart failure with mildly reduced EF (HFmrEF) or preserved EF (HFpEF). The TOPCAT trial, which evaluated spironolactone versus placebo in patients with HFmrEF/HFpEF, yielded equivocal results for the primary composite outcome of cardiovascular mortality and heart failure hospitalizations. However, post hoc analyses revealed that geographic heterogeneity in patient phenotype, treatment adherence, and event rates complicated interpretation of the study. Thus, spironolactone’s role in the treatment of HFpEF remains uncertain, particularly given safety concerns regarding hyperkalemia and worsening renal function. Given finerenone’s favorable safety profile and potent antifibrotic effects, this novel nonsteroidal MRA may represent a therapeutic advance, particularly for patients with cancer or cancer survivors. Therefore, clarifying the potential benefit of finerenone over spironolactone in cancer populations with HFmrEF/HFpEF is of considerable clinical interest.
In a recent issue of the AJC , Mancini et al. evaluated the association of finerenone use with heart failure hospitalizations and significant hyperkalemia events compared with spironolactone. Using the large multicenter TriNetX electronic health record database, the authors identified patients with concomitant heart failure, a history of cancer, and MRA use. This retrospective observational cohort study employed a propensity score–matching approach that balanced numerous baseline characteristics between groups, thereby mitigating measured confounding. The primary outcomes were the incidence of acute-on-chronic heart failure and severe hyperkalemia, defined by ICD-10 coding and serum potassium >5.5 mmol/L, respectively. Secondary outcomes included major adverse cardiovascular events (MACE), all-cause mortality, acute renal failure, ventricular arrhythmias, and new-onset atrial fibrillation. After matching, 872 patients were included (mean age 72 years; 45% women; 50% White; 23% receiving chemotherapy; 69% with chronic kidney disease; and 90% with diabetes). Among patients with a history of cancer and heart failure (LVEF ≥40%), finerenone use was associated with lower rates of heart failure exacerbation, all-cause mortality, severe hyperkalemia, and renal failure over 1 year compared with spironolactone. The incidences of new-onset atrial fibrillation, cerebrovascular accident, and ventricular arrhythmias did not differ significantly between cohorts; however, composite MACE was lower with finerenone, driven primarily by fewer heart failure events.
These results suggest potential clinical benefits of finerenone in patients with a history of cancer and HFmrEF/HFpEF in real-world practice. Notably, finerenone use was associated with lower all-cause mortality at 1 year in this vulnerable cardio-oncology population. A large nationwide cohort study by Almas et al., also using the TriNetX database, similarly demonstrated that finerenone was associated with a significantly lower risk of heart failure exacerbations compared with spironolactone in patients with HFpEF, along with a more favorable hyperkalemia profile. These findings are consistent with the current study and support the potential clinical utility of finerenone across a broader range of heart failure phenotypes, including consideration of finerenone as a preferred MRA in cardio-oncology patients with heart failure and LVEF ≥40%.
The authors should be congratulated for conducting the first study to demonstrate the clinical benefits of finerenone compared with spironolactone in a cohort of patients with cancer. However, several caveats warrant consideration. First, the study identified patients with any history of malignant neoplasm using ICD-10 codes, encompassing those with active or relapsed cancer as well as cancer survivors, thereby approximating a real-world cardio-oncology population. Yet, detailed information on cancer type, stage, and specific treatment was unavailable. Among the matched cohort, only 23% had received chemotherapy, which may have contributed to CTRCD, and the predominant etiology of heart failure was not clarified. Second, despite propensity matching, residual confounding from unmeasured variables cannot be excluded. Before matching, the finerenone cohort (n = 464) was substantially smaller than the spironolactone cohort (n = 64,961), raising the possibility of channeling bias and formulary effects. Patients initiated on finerenone tended to have more comorbidities, such as diabetes and chronic kidney disease, in the prematched cohort. These baseline characteristics may reflect current prescribing patterns, given that finerenone has primarily been approved for diabetic kidney disease. Third, the TriNetX database does not reliably capture medication discontinuation dates or reasons for therapy changes, such as hyperkalemia, making it difficult to determine whether finerenone was used as initial therapy or after prior MRA exposure. Fourth, survivor bias and prevalent-user bias also cannot be excluded, as patients must have survived long enough to be prescribed finerenone. Fifth, detailed echocardiographic parameters, including quantitative LVEF, were not uniformly available, limiting the ability to stratify by heart failure phenotype—an important consideration given the heterogeneity of HFmrEF and HFpEF. The findings may not be generalizable to patients with HFrEF, which is more commonly associated with CTRCD. Finally, as a retrospective observational study, causality cannot be inferred despite robust statistical adjustment. These findings should therefore be viewed as hypothesis-generating within a coded HFmrEF/HFpEF population. A prospective, head-to-head randomized controlled trial of finerenone versus spironolactone in this specific population would be the definitive approach to confirm these observations.
CRediT authorship contribution statement
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
