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      Serum potassium level and mineralocorticoid receptor antagonist dose in a large cohort of chronic heart failure patients

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          Abstract

          Aims

          Hyperkalaemia is observed frequently in heart failure (HF) patients and is associated with an impaired prognosis and underuse of mineralocorticoid receptor antagonists (MRAs). However, the effects of serum potassium on prescription of the full guideline recommended daily dose of 50 mg in real‐world daily practice are unknown. Therefore, we investigated serum potassium and its association with the prescribed MRA dose in a large cohort of chronic HF patients.

          Methods and results

          A total of 5346 patients with chronic HF with a left ventricular ejection fraction ≤40% from 34 Dutch outpatient HF clinics between 2013 and 2016 were analysed on serum potassium and MRA (spironolactone and eplenerone) dose. Data were stratified by potassium as a serum potassium level <4.0, 4.0 to 5.0 or >5.0 mmol/L. Multivariable logistic regression models were used to assess the association between serum potassium and MRA dose and to adjust for potential confounders. Mean serum potassium was 4.4 ± 0.5 mmol/L and hyperkalaemia (serum potassium >5.0 mmol/L) was present in 399 patients (7.5%). MRA was used in 3091 patients (58.1%). Patients with hyperkalaemia significantly less often received ≥100% of the target dose (50 mg) compared with patients with a serum potassium between 4.0–5.0 mmol/L and <4.0 mmol/L (7.7% vs. 9.5% vs. 13.6% respectively, P = 0.0078). In the multivariable regression analyses, patients with hyperkalaemia were significantly less likely to receive ≥100% of the target dose compared with patients with serum potassium 4.0–5.0 mmol/L (OR 0.38, 95% CI 0.15–0.97, P = 0.044). Additionally, a one unit increase in serum potassium was significantly associated with a lower odds of receiving ≥100% of the target dose (OR 0.69, 95% CI 0.49–0.98, P = 0.036).

          Conclusions

          In this large registry of real‐world chronic HF patients, both an increase in serum potassium and hyperkalaemia were associated with a lower odds of receiving the guideline‐recommended MRA dose.

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          Most cited references34

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          2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure

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            The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators.

            Aldosterone is important in the pathophysiology of heart failure. In a doubleblind study, we enrolled 1663 patients who had severe heart failure and a left ventricular ejection fraction of no more than 35 percent and who were being treated with an angiotensin-converting-enzyme inhibitor, a loop diuretic, and in most cases digoxin. A total of 822 patients were randomly assigned to receive 25 mg of spironolactone daily, and 841 to receive placebo. The primary end point was death from all causes. The trial was discontinued early, after a mean follow-up period of 24 months, because an interim analysis determined that spironolactone was efficacious. There were 386 deaths in the placebo group (46 percent) and 284 in the spironolactone group (35 percent; relative risk of death, 0.70; 95 percent confidence interval, 0.60 to 0.82; P<0.001). This 30 percent reduction in the risk of death among patients in the spironolactone group was attributed to a lower risk of both death from progressive heart failure and sudden death from cardiac causes. The frequency of hospitalization for worsening heart failure was 35 percent lower in the spironolactone group than in the placebo group (relative risk of hospitalization, 0.65; 95 percent confidence interval, 0.54 to 0.77; P<0.001). In addition, patients who received spironolactone had a significant improvement in the symptoms of heart failure, as assessed on the basis of the New York Heart Association functional class (P<0.001). Gynecomastia or breast pain was reported in 10 percent of men who were treated with spironolactone, as compared with 1 percent of men in the placebo group (P<0.001). The incidence of serious hyperkalemia was minimal in both groups of patients. Blockade of aldosterone receptors by spironolactone, in addition to standard therapy, substantially reduces the risk of both morbidity and death among patients with severe heart failure.
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              ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC.

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                Author and article information

                Contributors
                j.brugts@erasmusmc.nl
                Journal
                ESC Heart Fail
                ESC Heart Fail
                10.1002/(ISSN)2055-5822
                EHF2
                ESC Heart Failure
                John Wiley and Sons Inc. (Hoboken )
                2055-5822
                03 February 2023
                April 2023
                : 10
                : 2 ( doiID: 10.1002/ehf2.v10.2 )
                : 1481-1487
                Affiliations
                [ 1 ] Department of Cardiology Erasmus MC, University Medical Center Rotterdam Rotterdam The Netherlands
                [ 2 ] Department of Cardiology Hospital Group Twente Hengelo The Netherlands
                [ 3 ] Department of Cardiology Hospital Rivierenland Tiel The Netherlands
                [ 4 ] Department of Cardiology Tergooi Blaricum The Netherlands
                [ 5 ] Department of Cardiology Zuwe Hofpoort Hospital Woerden The Netherlands
                [ 6 ] Department of Cardiology Scheper Hospital Emmen The Netherlands
                [ 7 ] Department of Cardiology Maastricht University Medical Center Maastricht The Netherlands
                Author notes
                [*] [* ]Correspondence to: Jasper J. Brugts, Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. Email: j.brugts@ 123456erasmusmc.nl
                Author information
                https://orcid.org/0000-0001-9752-6962
                Article
                EHF214285 ESCHF-22-00628
                10.1002/ehf2.14285
                10053159
                36738129
                b2dd0145-f677-4554-a7ac-0dfc1e8c55fa
                © 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 09 November 2022
                : 29 July 2022
                : 09 January 2023
                Page count
                Figures: 2, Tables: 3, Pages: 1487, Words: 2096
                Funding
                Funded by: Servier, the Netherlands
                Categories
                Short Communication
                Short Communications
                Custom metadata
                2.0
                April 2023
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.2.7 mode:remove_FC converted:29.03.2023

                heart failure,heart failure with reduced ejection fraction,hyperkalaemia,mineralocorticoid receptor antagonists,renin‐angiotensin‐aldosterone system inhibitors,guidelines

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