Finerenone versus spironolactone in heart failure with reduced ejection fraction and underlying diabetes mellitus with chronic kidney disease: A propensity-matched analysis

Hypothesis/Introduction Mineralocorticoid receptor antagonists (MRAs) are a cornerstone of therapy for heart failure with reduced ejection fraction (HFrEF), but comparative effectiveness between steroidal and nonsteroidal agents remains unclear. We hypothesized that finerenone would be associated with lower risk of cardiovascular outcomes compared with spironolactone in patients with HFrEF and type 2 diabetes mellitus (T2DM) with chronic kidney disease (CKD). Materials and Methods We conducted a retrospective cohort study using the TriNetX research network. Adults with HFrEF, T2DM, and CKD receiving finerenone or spironolactone were propensity score matched 1:1. Primary outcomes were major adverse cardiovascular events (MACE) and heart failure (HF) exacerbation. Secondary outcomes were major arrhythmic events, hyperkalemia, and acute kidney injury. Results Among 1055 patients in each group, finerenone was associated with a 17.6% lower risk of MACE (hazard ratio [HR] 0.824 [0.734, 0.925]; p < 0.001) and 19.7% lower risk of HF exacerbation (HR 0.803 [0.705, 0.915]; p < 0.001), with similar adverse effect rates. Conclusions Finerenone was associated with lower risks of MACE and HF exacerbation than spironolactone. However, finerenone and spironolactone are prescribed in different clinical settings, and propensity score matching and sensitivity analyses cannot overcome confounding by indication or residual confounding. The findings are hypothesis-generating and require prospective validation.