Non-steroidal mineralocorticoid receptor antagonists in cardiorenal disease

Author:

Pandey Arjun K1,Bhatt Deepak L2,Cosentino Francesco3ORCID,Marx Nikolaus4ORCID,Rotstein Ori5,Pitt Bertram6,Pandey Ambarish7,Butler Javed8ORCID,Verma Subodh9ORCID

Affiliation:

1. Michael G. DeGroote School of Medicine, McMaster University , Hamilton, ON , Canada

2. Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School , USA

3. Cardiology Unit, Department of Medicine Solna, Karolinska Institute & Karolinska University Hospital , Stockholm , Sweden

4. Department of Internal Medicine I, Cardiology, University Hospital Aachen, RWTH Aachen University , Aachen , Germany

5. Department of Surgery, St Michael's Hospital, University of Toronto , Toronto, ON , Canada

6. Department of Medicine, University of Michigan School of Medicine , Ann Arbor, MI , USA

7. Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center , Dallas, TX , USA

8. Department of Medicine, University of Mississippi School of Medicine , Jackson, MS , USA

9. Division of Cardiac Surgery, St Michael's Hospital, University of Toronto , Toronto, ON , Canada

Abstract

Abstract Despite existing treatments, patients with heart failure and chronic kidney disease (CKD) remain at high risk for adverse outcomes and progression to end-stage disease. Steroidal mineralocorticoid receptor antagonists (MRAs) such as spironolactone and eplerenone reduce mortality but remain under-prescribed due to the perceived risk of hyperkalaemia and hormonal side effects. The discovery of non-steroidal MRAs represents a major new dimension in cardiorenal disease therapy. Non-steroidal MRAs have high affinity and specificity for the mineralocorticoid receptor (MR) and differ from both steroidal agents and each other with respect to important physiochemical, pharmacodynamic, and pharmacokinetic parameters. Similar to their steroidal counterparts, they have beneficial anti-inflammatory, anti-remodelling, and anti-fibrotic properties in the kidneys, heart, and vasculature. There are several non-steroidal MRAs under development and clinical assessment; of these, only esaxerenone and finerenone are approved for treatment globally. In Japan, esaxerenone is approved for essential hypertension and has been studied in diabetic nephropathy. Compared with steroidal MRAs, finerenone more potently inhibits MR co-regulator recruitment and fibrosis and distributes more evenly between the heart and kidneys. The landmark Phase III trials FIGARO-DKD and FIDELIO-DKD demonstrated that finerenone-reduced major kidney and cardiovascular events on top of maximally tolerated renin–angiotensin–aldosterone system inhibition in patients with CKD associated with Type 2 diabetes. Non-steroidal MRAs are currently under evaluation in heart failure and for synergistic treatment with sodium–glucose contransporter 2 inhibitors. These ground-breaking agents could become an important therapy across the spectrum of cardiorenal disease.

Publisher

Oxford University Press (OUP)

Subject

Cardiology and Cardiovascular Medicine

Cited by 25 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3