Key Points

In three trials, finerenone reduced a range of cardiovascular and kidney outcomes in persons with diabetes and CKD.Benefits of finerenone were observed across a broad spectrum of glycemia and kidney structure and function.In exploratory analyses, cardiovascular benefits of finerenone appeared consistent in CKD populations without diabetes.

Background

Finerenone has been shown to reduce cardiovascular and kidney events in individuals with CKD and type 2 diabetes. Pooling data from all completed outcomes trials evaluating finerenone to date may enhance understanding of its effects on morbidity and mortality in this high-risk population.

Methods

In this prespecified participant-level pooled analysis of the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease (FIDELIO-DKD), Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD), and Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients with Heart Failure (FINEARTS-HF) trials (FINE-HEART), FINEARTS-HF participants with type 2 diabetes, CKD, and albuminuria were pooled with persons enrolled in FIDELIO-DKD and FIGARO-DKD. Treatment effects of finerenone versus placebo on cardiovascular events, composite kidney outcomes, all-cause hospitalization, and mortality were evaluated using Cox proportional hazards regression models, stratified by trial and geographic region.

Results

Among 18,991 pooled trial participants, 14,180 (mean age, 65±10 years; 31% female; mean eGFR, 58±22 ml/min per 1.73 m2; median urine albumin-to-creatinine ratio (UACR), 478 [interquartile range, 167–1103] mg/g) were included in the analysis. Finerenone reduced cardiovascular death or heart failure hospitalization (hazard ratio, 0.83; 95% confidence interval, 0.75 to 0.93; P = 0.001) compared with placebo, without evidence of heterogeneity according to baseline eGFR (Pinteraction = 0.18), UACR (Pinteraction = 0.60), or glycated hemoglobin (Pinteraction = 0.51). Finerenone additionally appeared to reduce cardiovascular death, heart failure hospitalization, major adverse cardiovascular events, new-onset atrial fibrillation, and the composite kidney outcome. Benefits on the composite kidney outcome appeared greater with higher baseline UACR (Pinteraction = 0.04). In sensitivity analyses evaluating a broader range of participants with CKD, finerenone appeared to consistently reduce cardiovascular death or heart failure hospitalization irrespective of (1) UACR (Pinteraction = 0.22) when FINEARTS-HF participants with type 2 diabetes and at least moderate-risk CKD were included and (2) glycated hemoglobin (Pinteraction = 0.59) when FINEARTS-HF participants with albuminuric CKD but without diabetes were included. Serious adverse events were less common with finerenone versus placebo (34% versus 36%), but hyperkalemia-related permanent treatment discontinuations were more common (2% versus 1%).

Conclusions

In this prespecified FINE-HEART analysis, finerenone reduced cardiovascular, kidney, and mortality events across a wide spectrum of CKD in persons with type 2 diabetes.

Clinical Trial registry name and registration number:

PROSPERO, CRD42024570467