Key result
Finerenone linked to ~59% lower 1-year mortality vs spironolactone in HFpEF and CKD.
Why the study?
The role of MRAs in patients with HFpEF and CKD remains limited, and no head-to-head study had evaluated cardiorenal outcomes in patients with both HFpEF and established CKD initiating finerenone versus spironolactone.
Does finerenone reduce all-cause mortality, hospitalizations, acute kidney injury, hyperkalemia, and acute decompensated heart failure compared to spironolactone in patients with HFpEF and Stage 3+ CKD?
Cohort (n=888)
Does finerenone reduce all-cause mortality, hospitalizations, acute kidney injury, hyperkalemia, and acute decompensated heart failure compared to spironolactone in patients with HFpEF and Stage 3+ CKD?
In a propensity-matched cohort of patients with comorbid HFpEF and Stage 3+ CKD, finerenone was associated with lower 1-year all-cause mortality, fewer HF hospitalizations, and lower rates of hyperkalemia and acute kidney injury compared with spironolactone.
Finerenone may be preferable to spironolactone in HFpEF-CKD; hypothesis-generating and challenges prior preference pending RCTs.
Introduction Heart failure with preserved ejection fraction (HFpEF) and chronic kidney disease (CKD) are frequently comorbid and worsen cardiorenal outcomes. Mineralocorticoid receptor antagonists (MRAs) have not consistently been shown to improve cardiovascular outcomes among patients with HFpEF, and their role in patients with CKD remains limited. The TOPCAT Trial suggests reduced HF hospitalizations with spironolactone. The FINEARTS-HF trial demonstrated that finerenone, a nonsteroidal MRA, reduces HF events and cardiovascular death in patients with LVEF ≥40%. Although real-world data suggest a potential superiority of finerenone over steroidal MRAs in HFpEF, no head-to-head study has evaluated cardiorenal outcomes in patients with both HFpEF and established CKD initiating finerenone versus spironolactone [1]. Purpose This study aims to compare the incidence of all-cause mortality (ACM), acute kidney injury (AKI), hyperkalemia, and recurrent acute decompensated heart failure (ADHF) in patients with HFpEF and Stage 3+ CKD who initiated either finerenone or spironolactone. Methods Using TriNetX, we conducted a retrospective cohort analysis of patients with documented HFpEF (I50.3) and CKD3+ (N18.3) initiated on either Spironolactone or Finerenone between 2020 and 2025. We excluded patients with systolic (I50.2) or combined heart failure (I50.4). Outcomes were assessed over a year following initiation of MRA. We performed a 1:1 propensity score matching on age, sex, race, ethnicity, and all AHA PREVENT variables. Primary endpoints included ACM and hospitalization, AKI, hyperkalemia, and ADHF events. Z-tests were performed using risk differences; Cox regression was used to compute hazard ratios over 1 year. Results Propensity matching resulted in two well-balanced cohorts (n=444 each) with a mean age of 68 years (49% female, 62% white). Over 1 year follow-up, patients who initiated finerenone had significantly improved outcomes compared to the spironolactone group [Figure 1]. Finerenone was associated with a lower risk of ACM (5.9% vs 13.3%; HR 0.413, 95% CI: 0.260-0.655, p=0.018) and greater time to all-cause hospitalization (HR 0.748, 95% CI: 0.615-0.910, p<0.001). The finerenone cohort showed fewer adverse cardiorenal outcomes, including AKI (32.2% vs 45.5%; HR 0.602, 95% CI: 0.486-0.746, p<0.001), hyperkalemia (18% vs 24.1%; HR 0.679, 95% CI: 0.508-0.907, p=0.026), and ADHF events (20.5% vs 33.8%; HR 0.514, 95% CI: 0.396-0.667, p=0.002). Conclusion In patients with comorbid HFpEF and CKD3+, finerenone may offer improved cardiorenal outcomes and a superior safety profile compared with spironolactone. These findings challenge the reluctance to use MRAs in HFpEF with CKD, positioning finerenone as a safer therapeutic alternative. Notably, the magnitude of benefit appears consistent with prior head-to-head analyses in broader HFpEF populations, suggesting CKD3+ does not significantly modify finerenones' relative efficacy [1].
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Agu et al. (2026) conducted a cohort in Heart failure with preserved ejection fraction (HFpEF) and Stage 3+ chronic kidney disease (CKD) (n=888). Finerenone vs. Spironolactone was evaluated on All-cause mortality (co-primary with all-cause hospitalization, acute kidney injury, hyperkalemia, and acute decompensated heart failure) (HR 0.413, 95% CI 0.260-0.655, p=0.018). Finerenone vs spironolactone in HFpEF and CKD3+ was associated with lower 1-year all-cause mortality (5.9% vs 13.3%; HR 0.413, 95% CI 0.260-0.655, p=0.018) and fewer cardiorenal events.
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