Abstract Body (Do not enter title and authors here): BACKGROUND:
Mineralocorticoid receptor antagonists (MRAs) mechanistically reduce inflammation, oxidative stress and endothelial dysfunction. There is growing interest in understanding the composite cardiovascular (CV) protection afforded by therapies like the nonsteroidal MRA finerenone with systemic actions in patients with cardio-kidney-metabolic (CKM) syndrome.

METHODS:
In this participant-level pre-specified pooled analysis from three large phase 3 clinical trials (FIDELIO-DKD, FIGARO-DKD, and FINEARTS-HF), we assessed the association between various nonfatal CV events (myocardial infarction, stroke, and heart failure hospitalization) and rates of subsequent mortality using time-updated models. We then examined the treatment effects of finerenone vs. placebo on major adverse cardiovascular events (MACE, a composite of CV death, nonfatal myocardial infarction, nonfatal stroke, or heart failure hospitalization), which was a prespecified secondary endpoint in the FINE-HEART pooled analysis, using Cox regression models stratified by trial and region.

RESULTS:
During a median of 2.9 years of follow-up, among the 18,991 participants, 1,544 (8.1%) experienced heart failure hospitalization, 500 (2.6%) nonfatal myocardial infarction, 570 (3.0%) nonfatal stroke, and 892 (4.7%) CV death. Patients with incident myocardial infarction, stroke, and heart failure hospitalization consistently experienced markedly higher subsequent risks of mortality (Figure 1). Mortality was highest after heart failure hospitalization (incidence rate 23.4 [21.4-25.8] per 100py compared with 3.2 [3.1-3.4] per 100py for individuals without nonfatal CV events). Finerenone reduced the composite of CV death, nonfatal myocardial infarction, nonfatal stroke, or heart failure hospitalization (HR 0.91; 95% CI, 0.85–0.98; P = 0.010, Figure 2). Results were essentially unchanged in a sensitivity analysis including undetermined deaths as CV deaths (HR 0.90; 95% CI, 0.84–0.96; P = 0.002). The treatment effect on MACE was consistent across FINEARTS-HF (HR 0.95; 95% CI 0.86–1.05), FIDELIO-DKD (HR 0.88; 95% CI 0.76–1.02), and FIGARO-DKD (HR 0.87; 95% CI 0.76–1.00); P_int=0.55. Risk reductions did not differ by the number of CKM conditions (P_int=0.98).

CONCLUSION
Among patients with cardio-kidney-metabolic syndrome, major adverse cardiovascular events were frequent, prognostically meaningful, and reduced with the non-steroidal MRA finerenone.