TOPLINE

Among patients with type 2 diabetes (T2D) and chronic kidney disease (CKD), finerenone consistently reduced the risk for adverse cardiovascular and kidney outcomes compared with placebo, regardless of the cardiovascular-kidney-metabolic (CKM) syndrome stage at baseline.

METHODOLOGY

• CKM syndrome is defined as the interplay of obesity, diabetes, CKD, and cardiovascular disease (CVD), with finerenone previously showing cardiovascular and kidney benefits in patients with T2D and CKD.
• Researchers conducted a pooled analysis of two randomized phase 3 trials to evaluate the efficacy and safety of finerenone across CKM stages and its effects on CKM syndrome progression and regression over time in patients with T2D and CKD.
• A total of 12,990 patients (mean age, 64.8 years; 70% male) with a serum potassium level ≤ 4.8 mmol/L who were receiving maximally tolerated renin-angiotensin system inhibitor therapy were included; patients were randomly assigned to receive finerenone or placebo, and those with symptomatic heart failure with reduced ejection fraction were excluded.
• Patients were categorized by the CKM stage at baseline: stage II (metabolic risk factors or moderate- to high-risk CKD; n = 3864), stage III (very high-risk CKD; n = 3275), and stage IV (clinical CVD; n = 5851).
• The primary endpoints were a cardiovascular composite outcome (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or heart failure hospitalization) and a kidney composite outcome (kidney failure, sustained ≥ 57% decrease in the estimated glomerular filtration from baseline over ≥ 4 weeks, or death from kidney failure); the median follow-up duration was 3 years.

TAKEAWAY

• CKM stage IV was associated with a higher risk for the composite cardiovascular outcome (adjusted hazard ratio [aHR], 1.87; 95% CI, 1.56-2.24) and the composite kidney outcome (aHR, 1.96; 95% CI, 1.43-2.69) than CKM stage II.
• Finerenone reduced the composite cardiovascular (P for interaction = .86) and kidney (P for interaction = .65) outcomes, regardless of the CKM stage at baseline.
• Patients in the finerenone group had 66% higher odds of experiencing CKM regression from stage III to stage II than those in the placebo group (P < .001) and were less likely to experience CKM stage progression from baseline, with borderline statistical significance (P = .05).
• The safety profile of finerenone was similar across CKM stages, with no differential risk for hyperkalemia by stage.

IN PRACTICE

“These findings highlight the applicability of the CKM syndrome construct to clinical trial settings, illustrate the dynamic temporal flexibility of CKM syndrome, and extend understanding of the benefits of finerenone on interrelated CKM health pathways in persons with CKD and T2D,” the authors of the study wrote.

SOURCE

The study was led by Kevin Bryan Lo, MD, MS, Brigham and Women’s Hospital and Harvard Medical School, Boston. It was published online as a brief report in JAMA Cardiology.

LIMITATIONS

The FIDELITY trials were not originally designed to investigate the effects of finerenone on CKM syndrome. As a result, some subgroups had limited sample sizes, and not all data required for complete CKM stage classification were systematically collected.

DISCLOSURES

The trials were funded by Bayer AG. Three authors reported being employees of Bayer AG, and one author also reported holding shares in the company. Several authors reported receiving grants or grants to their institution, personal or consulting fees, nonfinancial support, or lecture fees; having advisory roles; holding patents or patent applications; and having other relationships with multiple pharmaceutical companies and institutions, including Bayer AG.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.