Finerenone Across Cardiovascular-Kidney-Metabolic Syndrome Stages: Post Hoc Analysis of the FIDELITY Randomized Clinical Trials.

Finerenone is a nonsteroidal mineralocorticoid receptor antagonist that has improved outcomes in type 2 diabetes (T2D) and CKD.

Finerenone 是一种非甾体类盐皮质激素受体拮抗剂，已在2型糖尿病（T2D）和慢性肾脏病（CKD）中改善了结果。

Background

To evaluate the efficacy and safety of finerenone across CKM stages, and to examine the effects of finerenone on CKM syndrome progression and regression over time.

评估非奈利酮在慢性肾脏病（CKD）各阶段的疗效和安全性，并检查非奈利酮对CKD综合征进展和逆转随时间的影响。

DESIGN, SETTING, AND PARTICIPANTS: This study is a post hoc pooled analysis of 2 randomized, double-blind, placebo-controlled, phase 3 multinational, multicenter clinical trials (FIDELITY) and was conducted across 48 countries.

设计、环境和参与者：本研究是对两项随机、双盲、安慰剂对照的第三阶段多国多中心临床试验（FIDELITY）的事后汇总分析，研究在48个国家进行。

Patients with T2D and CKD with estimated glomerular filtration rate (eGFR) 25 mL/min/1.73 m2 or higher, serum potassium 4.8 mmol/L or less, and taking maximally tolerated renin angiotensin system inhibitor therapy were included and classified into CKM syndrome stages, using American Heart Association criteria.

纳入了患有2型糖尿病和慢性肾脏病的患者，这些患者的估算肾小球滤过率(eGFR)为25 mL/min/1.73 m2或更高，血清钾为4.8 mmol/L或更低，并且正在接受最大耐受剂量的肾素-血管紧张素系统抑制剂治疗。这些患者根据美国心脏协会的标准被分类为CKM综合征的各个阶段。

These data were analyzed from September 2025 and March 2026.

这些数据的分析是从2025年9月到2026年3月进行的。

intervention

Participants in the pooled trials were randomly assigned to either finerenone or placebo.

合并试验中的参与者被随机分配到finerenone组或安慰剂组。

main_outcomes_and_measures

Cardiovascular composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or heart failure hospitalization and a kidney composite outcome of kidney failure, a sustained 57% or more decrease in eGFR from baseline over 4 weeks or more, or death from kidney failure.

心血管复合终点包括心血管死亡、非致命性心肌梗死、非致命性中风或心力衰竭住院，以及肾脏复合结果包括肾衰竭、从基线开始4周或更长时间内eGFR持续下降57%或更多，或因肾衰竭死亡。

Results

Among 12 990 participants (mean [SD] age, 64.8 [9.5] years; 3932 women [30%] and 9058 men [70%]) in FIDELITY, 3864 were classified as CKM stage 2 (30%), 3275 stage 3 (25%), and 5851 stage 4 (45%).

在FIDELITY研究中，共有12990名参与者（平均年龄[标准差]为64.8[9.5]岁；女性3932人[30%]，男性9058人[70%]），其中3864人被归类为CKM 2期（30%），3275人为3期（25%），5851人为4期（45%）。

After a median follow-up of 3 years, stage 4 was associated with a higher incidenceof cardiovascular events (adjusted hazard ratio[aHR], 1.87; 95% CI, 1.56-2.24) and kidney events (aHR, 1.96; 95% CI, 1.43-2.69) when compared with stage 2.

经过中位随访3年后，与2期相比，4期与更高的心血管事件发生率相关（调整后风险比[aHR]，1.87；95%置信区间[CI]，1.56-2.24），以及更高的肾脏事件发生率（aHR，1.96；95% CI，1.43-2.69）。

Finerenone consistently reduced cardiovascular (P for interaction = .86) and kidney (P for interaction = .65) events, irrespective of baseline CKM stage.

无论基线 CKM 阶段如何，Finerenone 一致地降低了心血管 (P for interaction = .86) 和肾脏 (P for interaction = .65) 事件。

Absolute rate reductions for the composite cardiovascular outcome were -1.1 per 100 person-years for stage 4 and -0.4 per 100 person-years for stage 2.

复合心血管结果的绝对率降低为 CKM 4 期每 100 人年 -1.1，CKM 2 期每 100 人年 -0.4。

After 3 years, participants randomized to finerenone were more likely to experience CKM syndrome regression (11.4% vs 7.4%; adjusted odds ratio [aOR], 1.66; 95% CI, 1.30-2.13; P < .001) and less likely to experience CKM syndrome progression (aOR, 0.89; 95% CI, 0.79, 1.00; P = .05) vs placebo.

3年后，被随机分配到finerenone的参与者更有可能经历CKM综合征的缓解（11.4%对比7.4%；调整后的优势比[aOR]，1.66；95%置信区间[CI]，1.30-2.13；P < .001），并且相比于安慰剂，他们经历CKM综合征进展的可能性更小（aOR，0.89；95% CI，0.79至1.00；P = .05）。

conclusions_and_relevance

Among patients with T2D and CKD in this study, finerenone reduced risks of cardiovascular and kidney events across CKM stages and led to greater CKM syndrome regression, and lesser CKM syndrome progression, over time.

在这项研究中，患有2型糖尿病和慢性肾脏病的患者中，finerenone降低了心血管和肾脏事件的风险，这些风险跨越CKM各个阶段，并随着时间的推移导致更大的CKM综合征缓解和更小的CKM综合征进展。

trial_registration

ClinicalTrials.gov Identifier: NCT02540993 and NCT02545049.

临床试验注册号：NCT02540993和NCT02545049。