Eur J Heart Fail. 2026 May 5:xuag150. doi: 10.1093/ejhf/xuag150. Online ahead of print.
ABSTRACT
AIMS: Finerenone, a selective nonsteroidal mineralocorticoid receptor antagonist, has been shown to reduce cardiovascular (CV) and kidney events in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). We aimed to quantify the robustness of its CV benefits in phase 3 randomized controlled trials (RCTs) using fragility metrics coupled with conventional clinical effect measures.
METHODS AND RESULTS: We systematically searched MEDLINE and Scopus (from inception to June 2025) for phase 3 or 4 placebo-controlled RCTs of finerenone in T2DM and CKD reporting dichotomous CV outcomes. Three trials were included: FIDELIO-DKD, FIGARO-DKD, and the pooled FIDELITY analysis. We extracted hazard ratios (HRs), absolute risk reduction (ARR), relative risk reduction (RRR), number needed to treat (NNT), fragility index (FI), reverse fragility index (RFI), fragility quotient (FQ), and reverse fragility quotient (RFQ) for the primary composite CV outcome (CV death, non-fatal myocardial infarction [MI], non-fatal stroke, heart failure hospitalization [HFH]) and individual components. The primary composite outcome was significantly reduced in FIDELIO-DKD (HR 0.86, NNT 56; FI 4, FQ 0.0007) and FIDELITY (HR 0.86, NNT 59; FI 38, FQ 0.002), but not FIGARO-DKD (HR 0.87; RFI 7, RFQ 0.0009). Among individual outcomes, HFH showed the most consistent and robust benefit (FIDELITY HR 0.78, NNT 91; FI 23, FQ 0.001). Effects on CV death, MI, and stroke were numerically favorable but statistically non-significant, with low RFIs (mostly 1-3, and up to 9).
CONCLUSIONS: Finerenone significantly reduces HF hospitalization and modestly improves composite CV outcomes in T2DM with CKD, but effects on CV death, MI, and stroke are fragile. Combining fragility metrics with standard efficacy measures offers a clearer view of the reliability of trial results.
PMID:42087276 | DOI:10.1093/ejhf/xuag150
