Abstract 4365801: Finerenone Reduces Sudden Death across the Spectrum of Cardio-Kidney-Metabolism: the FINE-HEART Pooled Analysis

Abstract

Background: Mineralocorticoid receptor antagonists (MRAs) mechanistically may alter pathways of cardiac fibrosis and electrical stability. The non-steroidal MRA finerenone has been shown to improve cardiovascular and kidney outcomes in patients with cardio-kidney-metabolic (CKM) syndrome, but its effects on cause-specific death, namely sudden death (SD), is uncertain. Methods: We conducted a participant-level pooled analysis of three large phase 3 trials of finerenone vs. placebo to evaluate the effect of the non-steroidal MRA finerenone on SD in participants with CKM syndrome. In this prespecified analysis, we pooled participants from 2 trials of chronic kidney disease with type 2 diabetes (FIDELIO-DKD and FIGARO-DKD) and a trial of HF with mildly reduced or preserved ejection fraction (FINEARTS-HF). SD was centrally adjudicated by the clinical endpoint committees. Independent predictors of SD were identified with multivariable Cox models using a stepwise forward selection. Treatment effects of finerenone (vs. placebo) were evaluated using Cox regression models stratified by region and trial. Results: Of the 18,991 participants, 418 (2.2%) (0.77 per 100 patient-years) experienced a SD during median follow-up of 2.9 years. An increased risk of SD was associated with age, male sex, a history of HF, lower estimated glomerular filtration rate, higher urine albumin/creatinine ratio, and lower baseline systolic blood pressure ( Panel A ). SD occurred in 188 (2.0%) participants randomized to finerenone and in 230 (2.5%) receiving placebo (HR 0.81, 95% CI 0.67, 0.98, p=0.034) ( Panel B ). Risk reductions were consistent irrespective of number of baseline CKM conditions (P interaction =0.93) and by trial (P interaction =0.71) ( Panel C ). Consistent results were observed analyzing non-SD as a competing risk (HR 0.81, 95% CI 0.67, 0.98, p=0.034). Conclusion: The non-steroidal MRA finerenone significantly reduced the risk of SD across the CKM spectrum.