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      Incidence, predictors and clinical management of hyperkalaemia in new users of mineralocorticoid receptor antagonists

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          Abstract

          Background

          Concerns for hyperkalaemia limit the use of mineralocorticoid receptor antagonists (MRAs). The frequency of MRA‐associated hyperkalaemia in real‐world settings and the extent of subsequent MRA discontinuation are poorly quantified.

          Methods and results

          Observational study including all Stockholm citizens initiating MRA therapy during 2007–2010. Hyperkalaemias were identified from all potassium (K +) measurements in healthcare. MRA treatment lengths and dosages were obtained from complete collection of pharmacy dispensations. We assessed the 1‐year incidence and clinical hyperkalaemia predictors, and quantified drug prescription changes after an episode of hyperkalaemia. Overall, 13 726 new users of MRA were included, with median age of 73 years, 53% women and median plasma K + of 3.9 mmol/L. Within a year, 18.5% experienced at least one detected hyperkalaemia (K + > 5.0 mmol/L), the majority within the first 3 monthsnthsnthsnthsnths of therapy. As a comparison, hyperkalaemia was detected in 6.4% of propensity‐matched new beta‐blocker users. Chronic kidney disease (CKD), older age, male sex, heart failure, peripheral vascular disease, diabetes and concomitant use of angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers, beta‐blockers and diuretics were associated with increased hyperkalaemia risk. After hyperkalaemia, 47% discontinued MRA and only 10% reduced the prescribed dose. Discontinuation rates were higher after moderate/severe (K + > 5.5 mmol/L) and early in therapy (<3 months from initiation) hyperkalaemias. CKD participants carried the highest risk of MRA discontinuation in adjusted analyses. When MRA was discontinued, most patients (76%) were not reintroduced to therapy during the subsequent year.

          Conclusion

          Among real‐world adults initiating MRA therapy, hyperkalaemia was very common and frequently followed by therapy interruption, especially among participants with CKD.

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          Most cited references34

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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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            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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              Patiromer in patients with kidney disease and hyperkalemia receiving RAAS inhibitors.

              Hyperkalemia increases the risk of death and limits the use of inhibitors of the renin-angiotensin-aldosterone system (RAAS) in high-risk patients. We assessed the safety and efficacy of patiromer, a nonabsorbed potassium binder, in a multicenter, prospective trial.
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                Author and article information

                Contributors
                juan.jesus.carrero@ki.se
                Journal
                Eur J Heart Fail
                Eur. J. Heart Fail
                10.1002/(ISSN)1879-0844
                EJHF
                European Journal of Heart Failure
                John Wiley & Sons, Ltd (Oxford, UK )
                1388-9842
                1879-0844
                18 April 2018
                August 2018
                18 April 2018
                : 20
                : 8 ( doiID: 10.1002/ejhf.2018.20.issue-8 )
                : 1217-1226
                Affiliations
                [ 1 ] Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden
                [ 2 ] Department of Statistics and Quantitative Methods University of Milano‐Bicocca Milan Italy
                [ 3 ] AstraZeneca Gaithersburg MD USA
                [ 4 ] Department of Clinical Science, Intervention and Technology Karolinska Institutet Stockholm Sweden
                [ 5 ] Department of Clinical Sciences Danderyd University Hospital, Karolinska Institutet Stockholm Sweden
                [ 6 ] Department of Medicine Karolinska Institutet Stockholm Sweden
                Author notes
                [*] [* ]Corresponding author. Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet, Nobels väg 12A, Box 281, 171 77 Stockholm, Sweden. Tel: +46 8 52482437, Email: juan.jesus.carrero@ 123456ki.se
                Article
                EJHF1199
                10.1002/ejhf.1199
                6607478
                29667759
                935a7510-0f8b-4387-8c3f-113e8651bd75
                © 2018 The Authors. European Journal of 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
                : 12 December 2017
                : 16 March 2018
                : 23 March 2018
                Page count
                Figures: 2, Tables: 3, Pages: 10, Words: 6487
                Funding
                Funded by: AstraZeneca to Karolinska Institutet
                Funded by: Swedish Heart and Lung Foundation
                Funded by: The Stockholm County Council
                Funded by: Baxter Healthcare
                Funded by: Vifor Fresenius Medical Care Renal Pharma
                Funded by: Martin Rind's and Westman's Foundations
                Funded by: Erasmus Traineeship Program
                Categories
                Research Article
                Research Articles
                Medical Therapy
                Research Article
                Custom metadata
                2.0
                ejhf1199
                August 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.4.4 mode:remove_FC converted:20.08.2018

                Cardiovascular Medicine
                renin–angiotensin–aldosterone system inhibitors,adverse drug events,heart failure,spironolactone

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