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

Abstract

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). 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. 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. 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 (P_interaction = 0.87) and by trial (P_interaction = 0.57). Participants with new-onset AF/AFL were at significantly higher subsequent risk of cardiovascular death, HF hospitalization, and adverse kidney outcomes. The nonsteroidal MRA finerenone reduced the risk of new-onset AF/AFL across the CKM spectrum.