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      Management of hyperkalemia during treatment with mineralocorticoid receptor blockers: findings from esaxerenone

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          Abstract

          The nonsteroidal mineralocorticoid receptor (MR) blocker esaxerenone has demonstrated good antihypertensive activity in a variety of patients, including those with uncomplicated grade I–III hypertension, hypertension with moderate renal dysfunction, hypertension with type 2 diabetes mellitus with albuminuria, and hypertension associated with primary aldosteronism. Hyperkalemia has long been recognized as a potential side effect occurring during treatment with MR blockers, but there is a lack of understanding and guidance about the appropriate management of hyperkalemia during antihypertensive therapy with MR blockers, especially in regard to the newer agent esaxerenone. In this article, we first highlight risk factors for hyperkalemia, including advanced chronic kidney disease, diabetes mellitus, cardiovascular disease, age, and use of renin-angiotensin-aldosterone system inhibitors. Next, we examine approaches to prevention and management, including potassium monitoring, diet, and the use of appropriate therapeutic techniques. Finally, we summarize the currently available data for esaxerenone and hyperkalemia. Proper management of serum potassium is required to ensure safe clinical use of MR blockers, including awareness of at-risk patient groups, choosing appropriate dosages for therapy initiation and dosage titration, and monitoring of serum potassium during therapy. It is critical that physicians take such factors into consideration to optimize MR blocker therapy in patients with hypertension.

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          Most cited references 121

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          Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study.

          The Randomized Aldactone Evaluation Study (RALES) demonstrated that spironolactone significantly improves outcomes in patients with severe heart failure. Use of angiotensin-converting-enzyme (ACE) inhibitors is also indicated in these patients. However, life-threatening hyperkalemia can occur when these drugs are used together. We conducted a population-based time-series analysis to examine trends in the rate of spironolactone prescriptions and the rate of hospitalization for hyperkalemia in ambulatory patients before and after the publication of RALES. We linked prescription-claims data and hospital-admission records for more than 1.3 million adults 66 years of age or older in Ontario, Canada, for the period from 1994 through 2001. Among patients treated with ACE inhibitors who had recently been hospitalized for heart failure, the spironolactone-prescription rate was 34 per 1000 patients in 1994, and it increased immediately after the publication of RALES, to 149 per 1000 patients by late 2001 (P<0.001). The rate of hospitalization for hyperkalemia rose from 2.4 per 1000 patients in 1994 to 11.0 per 1000 patients in 2001 (P<0.001), and the associated mortality rose from 0.3 per 1000 to 2.0 per 1000 patients (P<0.001). As compared with expected numbers of events, there were 560 (95 percent confidence interval, 285 to 754) additional hyperkalemia-related hospitalizations and 73 (95 percent confidence interval, 27 to 120) additional hospital deaths during 2001 among older patients with heart failure who were treated with ACE inhibitors in Ontario. Publication of RALES was not associated with significant decreases in the rates of readmission for heart failure or death from all causes. The publication of RALES was associated with abrupt increases in the rate of prescriptions for spironolactone and in hyperkalemia-associated morbidity and mortality. Closer laboratory monitoring and more judicious use of spironolactone may reduce the occurrence of this complication. Copyright 2004 Massachusetts Medical Society
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            K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease.

              (2004)
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              2013 ACCF/AHA Guideline for the Management of Heart Failure

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                Author and article information

                Contributors
                rakugi@geriat.med.osaka-u.ac.jp
                Journal
                Hypertens Res
                Hypertens Res
                Hypertension Research
                Springer Singapore (Singapore )
                0916-9636
                1348-4214
                20 November 2020
                20 November 2020
                2021
                : 44
                : 4
                : 371-385
                Affiliations
                [1 ]GRID grid.136593.b, ISNI 0000 0004 0373 3971, Department of Geriatric and General Medicine, , Osaka University Graduate School of Medicine, ; 2-2 Yamadaoka, Suita, Osaka 565-0871 Japan
                [2 ]GRID grid.410844.d, ISNI 0000 0004 4911 4738, Clinical Development Department III, , R&D Division, Daiichi Sankyo Co., Ltd., ; 1-2-58, Hiromachi, Shinagawa-ku, Tokyo 140-8710 Japan
                [3 ]GRID grid.410844.d, ISNI 0000 0004 4911 4738, Medical Science Department, , Daiichi Sankyo Co., Ltd., ; 3-5-1, Nihonbashi Honcho, Chuo-ku, Tokyo 103-8426 Japan
                Article
                569
                10.1038/s41440-020-00569-y
                8019656
                33214722
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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                Review Article
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                © The Japanese Society of Hypertension 2021

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