非奈利酮在慢性肾脏病和糖尿病患者中的肾脏功能/蛋白尿与心衰结局。

Finerenone and Heart Failure Outcomes by Kidney Function/Albuminuria in Chronic Kidney Disease and Diabetes.

机构信息

Department of Cardiology, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Department of Cardiology and Berlin Institute of Health Center for Regenerative Therapies, German Center for Cardiovascular Research Partner Site Berlin, Charité-Universitätsmedizin, Berlin, Germany.

出版信息

JACC Heart Fail. 2022 Nov;10(11):860-870. doi: 10.1016/j.jchf.2022.07.013. Epub 2022 Oct 12.

DOI:10.1016/j.jchf.2022.07.013

PMID:36328655

Abstract

BACKGROUND

In patients with type 2 diabetes (T2D), risks of cardiovascular mortality and heart failure (HF) increase with decreasing kidney function (estimated glomerular filtration rate [eGFR]) and increasing albuminuria (urine albumin-to-creatinine ratio [UACR]). Finerenone, a selective, nonsteroidal mineralocorticoid receptor antagonist, improved cardiorenal outcomes in patients with chronic kidney disease (CKD) and T2D in FIDELITY (Finerenone in Chronic Kidney Disease and Type 2 Diabetes: Combined FIDELIO-DKD and FIGARO-DKD Trial Programme Analysis).

OBJECTIVES

This study sought to evaluate the effects of finerenone on HF outcomes by eGFR and/or UACR categories.

METHODS

FIDELITY included 13,026 patients with T2D and CKD (UACR 30-5,000 mg/g and eGFR ≥25 mL/min/1.73 m) randomized to finerenone or placebo. Time-to-event outcomes were first hospitalization for heart failure (HHF), cardiovascular death or first HHF, recurrent HHF, and cardiovascular death or recurrent HHF, analyzed in subgroups by baseline eGFR (<60 and ≥60 mL/min/1.73 m) and/or UACR (<300 and ≥300 mg/g).

RESULTS

Compared with placebo, finerenone significantly reduced risk of first HHF (HR: 0.78 [95% CI: 0.66-0.92]; P = 0.003), cardiovascular death or first HHF (HR: 0.83 [95% CI: 0.74-0.93]; P = 0.002), recurrent HHF (HR: 0.79 [95% CI: 0.64-0.96]; P = 0.021), and cardiovascular death or recurrent HHF (HR: 0.82 [95% CI: 0.72-0.95]; P = 0.006). The risk of outcomes increased across baseline eGFR and UACR categories; lowest incidences were seen in patients with an eGFR ≥60 mL/min/1.73 m and a UACR <300 mg/g. Finerenone improved HF outcomes irrespective of baseline eGFR and/or UACR categories (all P interaction values >0.10).

CONCLUSIONS

Compared with placebo, finerenone improved HF-related outcomes in patients with CKD and T2D, with consistent benefits across eGFR and/or UACR categories. (Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease [FIDELIO-DKD], NCT02540993; Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Chronic Kidney Disease [FIGARO-DKD], NCT02545049).

摘要

背景

在 2 型糖尿病（T2D）患者中，心血管死亡率和心力衰竭（HF）的风险随着肾功能（估计肾小球滤过率[eGFR]）的降低和白蛋白尿（尿白蛋白与肌酐比[UACR]）的增加而增加。非奈利酮是一种选择性、非甾体类盐皮质激素受体拮抗剂，在 FIDELITY（非奈利酮在慢性肾脏病和 2 型糖尿病中的作用：联合 FIDELIO-DKD 和 FIGARO-DKD 试验项目分析）研究中改善了慢性肾脏病（CKD）和 T2D 患者的心脏肾脏结局。

目的

本研究旨在通过 eGFR 和/或 UACR 类别评估非奈利酮对 HF 结局的影响。

方法

FIDELITY 纳入了 13026 例 T2D 和 CKD 患者（UACR 30-5000mg/g 和 eGFR≥25mL/min/1.73m），随机分为非奈利酮或安慰剂组。首次心力衰竭（HFH）住院、心血管死亡或首次 HFH、复发性 HFH 和心血管死亡或复发性 HFH 的时间事件结局，按基线 eGFR（<60 和≥60mL/min/1.73m）和/或 UACR（<300 和≥300mg/g）进行亚组分析。

结果

与安慰剂相比，非奈利酮显著降低了首次 HFH 的风险（HR：0.78[95%CI：0.66-0.92]；P=0.003）、心血管死亡或首次 HFH（HR：0.83[95%CI：0.74-0.93]；P=0.002）、复发性 HFH（HR：0.79[95%CI：0.64-0.96]；P=0.021）和心血管死亡或复发性 HFH（HR：0.82[95%CI：0.72-0.95]；P=0.006）。基线 eGFR 和 UACR 类别越高，结局风险越高；在 eGFR≥60mL/min/1.73m 和 UACR<300mg/g 的患者中，发病率最低。非奈利酮改善了 HF 结局，无论基线 eGFR 和/或 UACR 类别如何（所有 P 交互值均>0.10）。

结论

与安慰剂相比，非奈利酮改善了 CKD 和 T2D 患者的 HF 相关结局，在 eGFR 和/或 UACR 类别中均具有一致的获益。（非奈利酮在 2 型糖尿病患者中的疗效和安全性研究[FIDELIO-DKD]，NCT02540993；非奈利酮在 2 型糖尿病患者和慢性肾脏病临床诊断中的疗效和安全性研究[FIGARO-DKD]，NCT02545049）。