在 4 期 CKD 合并 2 型糖尿病患者中使用非奈利酮的结局：FIDELITY 亚组分析。

Outcomes with Finerenone in Participants with Stage 4 CKD and Type 2 Diabetes: A FIDELITY Subgroup Analysis.

机构信息

Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Richard L. Roudebush VA Medical Center and Indiana University, Indianapolis, Indiana.

出版信息

Clin J Am Soc Nephrol. 2023 May 1;18(5):602-612. doi: 10.2215/CJN.0000000000000149. Epub 2023 Apr 7.

DOI:10.2215/CJN.0000000000000149

PMID:36927680

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10278789/

Abstract

BACKGROUND

Patients with stage 4 CKD and type 2 diabetes have limited treatment options to reduce their persistent cardiovascular and kidney risk. In Finerenone in Chronic Kidney Disease and Type 2 Diabetes (FIDELITY), a prespecified pooled analysis of Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease (FIDELIO-DKD) and Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD), finerenone improved heart-kidney outcomes in participants with CKD and type 2 diabetes.

METHODS

This FIDELITY subgroup analysis investigated the effects of finerenone in participants with stage 4 CKD (eGFR <30 ml/min per 1.73 m 2 ). Efficacy outcomes included a cardiovascular composite (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and a kidney composite (kidney failure, sustained ≥57% decrease in eGFR from baseline, or kidney disease death).

RESULTS

Of 13,023 participants, 890 (7%) had stage 4 CKD. The hazard ratio for risk of cardiovascular composite outcome with finerenone versus placebo was 0.78 (95% confidence interval, 0.57 to 1.07). The kidney composite outcome proportional hazards assumption was not met for the overall study period, with a protective effect only shown up to 2 years, after which the direction of association was inconsistent, and an observed loss of precision over time incurred on finerenone versus placebo risk differences. Nonetheless, albuminuria and rate of eGFR decline were consistently reduced with finerenone versus placebo. Adverse events were balanced between treatment arms. Hyperkalemia was the most common adverse event reported (stage 4 CKD: 26% and 13% for finerenone versus placebo, respectively); however, the incidence of hyperkalemia leading to permanent discontinuation was low (stage 4 CKD: 3% and 2% for finerenone versus placebo, respectively).

CONCLUSIONS

The cardiovascular benefits and safety profile of finerenone in participants with stage 4 CKD were consistent with the overall FIDELITY population; this was also the case for albuminuria and the rate of eGFR decline. The effects on the composite kidney outcome were not consistent over time.

摘要

背景

患有 4 期 CKD 和 2 型糖尿病的患者，其降低持续性心血管和肾脏风险的治疗选择有限。在非奈利酮减少慢性肾脏病和 2 型糖尿病患者的肾脏不良结局试验（FIDELIO-DKD）和非奈利酮减少 2 型糖尿病患者心血管死亡和发病率试验（FIGARO-DKD）的预先设定的非奈利酮汇总分析中，非奈利酮改善了 CKD 和 2 型糖尿病患者的心脏-肾脏结局。

方法

这项 FIDELITY 亚组分析调查了非奈利酮在 4 期 CKD （eGFR<30ml/min/1.73m2）患者中的疗效。主要疗效终点包括心血管复合终点（心血管死亡、非致死性心肌梗死、非致死性卒中和因心力衰竭住院）和肾脏复合终点（肾功能衰竭、eGFR 从基线持续下降≥57%或肾脏疾病死亡）。

结果

在 13023 名参与者中，890 名（7%）患有 4 期 CKD。与安慰剂相比，非奈利酮降低心血管复合终点风险的风险比为 0.78（95%置信区间，0.57 至 1.07）。在整个研究期间，肾脏复合终点的比例风险假设不成立，仅在 2 年内观察到保护作用，此后关联方向不一致，并且非奈利酮与安慰剂的风险差异随时间推移而观察到精度损失。尽管如此，与安慰剂相比，非奈利酮仍持续降低白蛋白尿和 eGFR 下降率。治疗组之间的不良事件平衡。高钾血症是最常见的不良事件（4 期 CKD：非奈利酮组为 26%，安慰剂组为 13%）；然而，导致永久停药的高钾血症发生率较低（4 期 CKD：非奈利酮组为 3%，安慰剂组为 2%）。