Effects of Finerenone on Sudden Death Across the Cardio-Kidney-Metabolic Landscape: A FINE-HEART Analysis.

We investigated independent predictors of SD and treatment effects of finerenone on SD.

我们研究了突发死亡（SD）的独立预测因素以及finerenone对突发死亡（SD）的治疗效果。

Methods

In this prespecified FINE-HEART analysis, we pooled participant-level data from 3 placebo-controlledtrials of finerenone in CKM syndrome, including 2 trials of chronic kidney disease with type 2 diabetes (FIDELIO-DKD [Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease] and FIGARO-DKD [Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease]) and a trial of heart failure with mildly reduced ejection fraction/heart failure with preserved ejection fraction (FINEARTS-HF [FINerenone trial to investigate Efficacy and sAfety superioR to placebo in paTientS with Heart Failure]).

在这项预先指定的FINE-HEART分析中，我们汇总了三项finerenone治疗CKM综合征的安慰剂对照试验的参与者级数据，包括两项针对2型糖尿病患者的慢性肾脏病试验（FIDELIO-DKD [在糖尿病肾病中减少肾功能衰竭和疾病进展的Finerenone]和FIGARO-DKD [在糖尿病肾病中减少心血管死亡和发病率的Finerenone]）以及一项针对轻度射血分数降低/保留射血分数的心力衰竭试验（FINEARTS-HF [FINerenone试验，研究Finerenone在射血分数降低/保留射血分数的心力衰竭患者中与安慰剂相比的有效性和安全性])。

SD in each trial was centrally adjudicated by a blinded clinical endpoint committee.

每个试验的标准差由一个盲法临床终点委员会集中判定。

We identified clinical predictors of SD in multivariable Cox regression models and examined treatment effects of finerenone on SD in Cox models stratified by region and trial.

我们通过多变量Cox回归模型识别了肾功能下降（SD）的临床预测因素，并在按地区和试验分层的Cox模型中检验了非甾体矿物皮质激素受体拮抗剂finerenone对肾功能下降的治疗效果。

Results

Of the 18,991 participants, 418 (2.2%) (0.77 per 100 patient-years) experienced SD during a median follow-up of 2.9 years.

在18,991名参与者中，有418人（占2.2%）（相当于每100患者年0.77人）在中位随访期为2.9年的期间内经历了肾功能下降（SD）。

Overall, rates of SD were higher in FINEARTS-HF than in the chronic kidney disease trials (1.5 vs 0.5 per 100 patient-years).

总体而言，FINEARTS-HF试验中稳定病情（SD）的发生率高于慢性肾脏病试验（每100患者年1.5例对比0.5例）。

For the pooled population, higher risk of SD was associated with older age, history of heart failure, atrial fibrillation, prior myocardial infarction, higher urine albumin-to-creatinine ratio, and lower baseline systolic blood pressure.

对于合并人群，更高的稳定病情（SD）风险与年龄较大、有心力衰竭病史、房颤、既往心肌梗死、较高的尿液白蛋白与肌酐比值以及较低的基线收缩压有关。

Randomization to finerenone reduced the risk of SD compared with placebo (HR: 0.81; 95% CI: 0.67-0.98; P = 0.034).

随机分配至非奈酮治疗组相比安慰剂组降低了肾病进展的风险（HR: 0.81; 95% 置信区间: 0.67-0.98; P = 0.034）。

Relative risk reductions were consistent across subgroups defined by number of baseline CKM conditions (Pinteraction = 0.93) and trial (Pinteraction = 0.71).

相对风险降低在基线时CKM条件数量定义的亚组（Pinteraction = 0.93）和试验（Pinteraction = 0.71）中保持一致。

Conclusions

The nonsteroidal mineralocorticoid receptor antagonist finerenone was associated with a lower risk of SD across the CKM spectrum.

非甾体盐皮质激素受体拮抗剂非瑞酮与慢性肾脏疾病（CKM）谱系中较低的SD风险相关。

(FINE-HEART: An Integrated Pooled Analysis of Finerenone across 3 Phase III Trials of Heart Failure and Chronic Kidney Disease and Type 2 Diabetes; CRD42024570467).

(FINE-HEART：对心力衰竭、慢性肾脏疾病和2型糖尿病的3项III期试验中非瑞酮的综合汇总分析；CRD42024570467)。