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依折麦布在伴或不伴2型糖尿病的慢性肾脏病高血压患者中的疗效与安全性:五项临床研究的汇总分析

Efficacy and safety of esaxerenone in hypertensive patients with chronic kidney disease, with or without type 2 diabetes mellitus: a pooled analysis of five clinical studies.

作者信息

Uchida Haruhito A, Wada Jun, Motoki Hirohiko, Kuwahara Koichiro, Kario Kazuomi, Katsuya Tomohiro, Shimosawa Tatsuo, Tsujita Kenichi, Suzuki Shoko, Suedomi Tomohiro, Taguchi Takashi

机构信息

Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

Department of Cardiovascular Medicine, Shinshu University School of Medicine, Nagano, Japan.

出版信息

Hypertens Res. 2025 Jun 30. doi: 10.1038/s41440-025-02259-z.

Abstract

Effective management of blood pressure (BP) and albuminuria are crucial for suppressing chronic kidney disease (CKD) progression and cardiovascular risks in hypertension. This pooled analysis evaluated the antihypertensive effects, organ-protective effects, and safety of esaxerenone in hypertensive patients with CKD by integrating five clinical studies of esaxerenone. Patients were divided based on type 2 diabetes mellitus (T2DM) status (with or without T2DM) and creatinine-based estimated glomerular filtration rate (eGFR) (30 to <60 and ≥60 mL/min/1.73 m). Significant changes in morning home BP from baseline at Week 12 were observed in the overall population (mean change -12.8/ - 5.4 mmHg), T2DM subgroups ( - 12.2/ - 4.5 and -14.5/ - 7.8 mmHg), and eGFR subgroups ( - 12.5/ - 4.7 and -14.0/ - 6.9 mmHg) (all P < 0.001). Bedtime home and office BP showed similar tendencies. Urine albumin-to-creatinine ratio significantly improved from baseline at Week 12 in the overall population (mean change: -55.2%), T2DM subgroups ( - 56.5% and -52.0%), and eGFR subgroups ( - 54.6% and -55.4%) (all P < 0.001). N-terminal pro-B-type natriuretic peptide levels significantly decreased in the overall population (percent change: -14.1%) and subgroup without T2DM ( - 25.3%). The incidence of serum potassium ≥5.5 mEq/L was lower in the subgroup with T2DM vs without T2DM (3.1% and 11.3%), potentially related to the use of sodium-glucose cotransporter 2 inhibitors. These findings highlight the sustained BP-lowering effect of esaxerenone throughout the day in hypertensive patients with CKD, irrespective of T2DM status, and its significant reduction in albuminuria. The data support the safety and efficacy of esaxerenone in this patient population, underscoring its potential as a valuable therapeutic option. This study showed that esaxerenone significantly lowered morning home, bedtime home, and office BP and UACR in hypertensive patients with CKD, regardless of T2DM status and kidney function (eGFR), and without any novel safety concerns. These highlight the efficacy, organ-protective effects, and safety of esaxerenone in hypertensive patients with CKD.

摘要

有效管理血压(BP)和蛋白尿对于抑制慢性肾脏病(CKD)进展以及高血压患者的心血管风险至关重要。这项汇总分析通过整合五项依普利酮的临床研究,评估了依普利酮在CKD高血压患者中的降压效果、器官保护作用及安全性。患者根据2型糖尿病(T2DM)状态(有或无T2DM)以及基于肌酐的估计肾小球滤过率(eGFR)(30至<60和≥60 mL/min/1.73 m²)进行分组。在总体人群(平均变化-12.8/-5.4 mmHg)、T2DM亚组(-12.2/-4.5和-14.5/-7.8 mmHg)以及eGFR亚组(-12.5/-4.7和-14.0/-6.9 mmHg)中,观察到第12周时清晨家庭血压较基线有显著变化(所有P<0.001)。就寝时家庭血压和诊室血压呈现相似趋势。总体人群、T2DM亚组以及eGFR亚组在第12周时尿白蛋白与肌酐比值较基线均显著改善(平均变化:-55.2%)(所有P<0.001)。总体人群以及无T2DM的亚组中N末端B型利钠肽原水平显著降低(百分比变化:-14.1%和-25.3%)。T2DM亚组血清钾≥5.5 mEq/L的发生率低于无T2DM亚组(3.1%和11.3%),这可能与使用钠-葡萄糖协同转运蛋白2抑制剂有关。这些发现突出了依普利酮在CKD高血压患者中全天持续的降压效果,无论T2DM状态如何,且其能显著降低蛋白尿。数据支持依普利酮在该患者群体中的安全性和有效性,强调了其作为一种有价值治疗选择的潜力。这项研究表明,依普利酮显著降低了CKD高血压患者的清晨家庭血压、就寝时家庭血压和诊室血压以及尿白蛋白与肌酐比值,无论T2DM状态和肾功能(eGFR)如何,且无任何新的安全问题。这些突出了依普利酮在CKD高血压患者中的疗效、器官保护作用及安全性。

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