Finerenone Reduces New-Onset Atrial Fibrillation Across the Spectrum of Cardio-Kidney-Metabolic Syndrome: The FINE-HEART Pooled Analysis

Background: Mineralocorticoid receptor antagonists (MRA) modulate cardiac and systemic pathways such as fibrosis and inflammation, which may contribute to the onset of atrial fibrillation (AF) or atrial flutter (AFL). Objectives: In this participant-level pooled analysis of 3 large clinical trials, the authors evaluated the effect of the nonsteroidal MRA finerenone on incident AF/AFL across the cardio-kidney-metabolic (CKM) spectrum. Methods: In this prespecified analysis, we pooled participants from 2 trials of chronic kidney disease and type 2 diabetes (FIDELIO-DKD and FIGARO-DKD) and a trial of heart failure (HF) with mildly reduced or preserved ejection fraction (FINEARTS-HF). Patients were randomized 1:1 to finerenone or placebo. New-onset AF/AFL was prospectively adjudicated in all trials by blinded clinical event committees. The risk of new-onset AF/AFL was evaluated using Cox regression models stratified by region and trial. Results: Among 14,581 patients who were free of AF/AFL at trial enrollment, 631 (4.3%) experienced new-onset AF/AFL during follow-up. Predictors of new-onset AF/AFL included older age, history of HF, higher body mass index, geographic region, and higher levels of urine albumin-to-creatinine ratio. During 2.9 years of median follow-up, new-onset AF/AFL occurred in 286 (3.9%) participants receiving finerenone and 345 (4.7%) assigned to placebo (HR: 0.83; 95% CI: 0.71-0.97; P = 0.019). Risk reductions were consistent irrespective of number of CKM conditions (Pinteraction = 0.87) and by trial (Pinteraction = 0.57). Participants with new-onset AF/AFL were at significantly higher subsequent risk of cardiovascular death, HF hospitalization, and adverse kidney outcomes. Conclusions: The nonsteroidal MRA finerenone reduced the risk of new-onset AF/AFL across the CKM spectrum.