J Am Coll Cardiol. 2026 Jun 3:S0735-1097(26)06417-X. doi: 10.1016/j.jacc.2026.04.045. Online ahead of print.
ABSTRACT
BACKGROUND: The nonsteroidal mineralocorticoid receptor antagonist finerenone has been shown to improve cardiovascular and kidney outcomes in patients with cardio-kidney-metabolic (CKM) syndrome, but its effects on sudden death (SD) are uncertain.
OBJECTIVES: We investigated independent predictors of SD and treatment effects of finerenone on SD.
METHODS: In this prespecified FINE-HEART analysis, we pooled participant-level data from 3 placebo-controlled trials of finerenone in CKM syndrome, including 2 trials of chronic kidney disease with type 2 diabetes (FIDELIO-DKD [Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease] and FIGARO-DKD [Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease]) and a trial of heart failure with mildly reduced ejection fraction/heart failure with preserved ejection fraction (FINEARTS-HF [FINerenone trial to investigate Efficacy and sAfety superioR to placebo in paTientS with Heart Failure]). SD in each trial was centrally adjudicated by a blinded clinical endpoint committee. We identified clinical predictors of SD in multivariable Cox regression models and examined treatment effects of finerenone on SD in Cox models stratified by region and trial.
RESULTS: Of the 18,991 participants, 418 (2.2%) (0.77 per 100 patient-years) experienced SD during a median follow-up of 2.9 years. Overall, rates of SD were higher in FINEARTS-HF than in the chronic kidney disease trials (1.5 vs 0.5 per 100 patient-years). For the pooled population, higher risk of SD was associated with older age, history of heart failure, atrial fibrillation, prior myocardial infarction, higher urine albumin-to-creatinine ratio, and lower baseline systolic blood pressure. Randomization to finerenone reduced the risk of SD compared with placebo (HR: 0.81; 95% CI: 0.67-0.98; P = 0.034). Relative risk reductions were consistent across subgroups defined by number of baseline CKM conditions (Pinteraction = 0.93) and trial (Pinteraction = 0.71).
CONCLUSIONS: The nonsteroidal mineralocorticoid receptor antagonist finerenone was associated with a lower risk of SD across the CKM spectrum. (FINE-HEART: An Integrated Pooled Analysis of Finerenone across 3 Phase III Trials of Heart Failure and Chronic Kidney Disease and Type 2 Diabetes; CRD42024570467).
PMID:42233928 | DOI:10.1016/j.jacc.2026.04.045