Skip to main content
Top
Published in: BMC Primary Care 1/2016

Open Access 01-12-2016 | Research article

Impact of hyperkalaemia definition on incidence assessment: implications for epidemiological research based on a large cohort study in newly diagnosed heart failure patients in primary care

Authors: Mar Martín-Pérez, Ana Ruigómez, Alexander Michel, Luis A. García Rodríguez

Published in: BMC Primary Care | Issue 1/2016

Login to get access

Abstract

Background

Various definitions of hyperkalaemia have been used in clinical research, and data from routine clinical practice on its incidence are sparse. We aimed to establish the incidence of hyperkalaemia in patients with newly diagnosed heart failure in the UK general population using different definitions for the condition.

Methods

We conducted a large retrospective cohort study using data from The Health Improvement Network primary care database. Patients with newly diagnosed heart failure (N = 19,194) were identified and followed until the first occurrence of hyperkalaemia. Different serum potassium (K+) thresholds were evaluated as possible definitions for hyperkalaemia, and incidence rates (IRs) calculated using a final operational definition both overall and among patient sub-groups.

Results

IRs of hyperkalaemia ranged from 0.92–7.93 per 100 person-years according to the definition. Based on considerable differences in the serum K+ normal range used between practices, 2176 (11.3 %) individuals were identified with a record of hyperkalaemia using our operational definition of a proportional increase of ≥10 % above the upper bound of the normal range: IR 2.90 per 100 person-years (95 % CI 2.78–3.02) over a mean follow-up of 3.91 years. Incidence rates were higher in older patients, and in those with diabetes or renal impairment.

Conclusions

Hyperkalaemia is a common finding in heart failure patients in primary care, but its incidence can vary nearly ten-fold depending on its definition. Since assessment of hyperkalaemia risk is essential for therapeutic decision making in heart failure patients, this finding warrants consideration in future epidemiological studies.
Literature
2.
go back to reference Juurlink DN, Mamdani MM, Lee DS, Kopp A, Austin PC, Laupacis A, et al. Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study. N Engl J Med. 2004;351:543–51.CrossRefPubMed Juurlink DN, Mamdani MM, Lee DS, Kopp A, Austin PC, Laupacis A, et al. Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study. N Engl J Med. 2004;351:543–51.CrossRefPubMed
3.
go back to reference Bozkurt B, Agoston I, Knowlton AA. Complications of inappropriate use of spironolactone in heart failure: when an old medicine spirals out of new guidelines. J Am Coll Cardiol. 2003;41:211–4.CrossRefPubMed Bozkurt B, Agoston I, Knowlton AA. Complications of inappropriate use of spironolactone in heart failure: when an old medicine spirals out of new guidelines. J Am Coll Cardiol. 2003;41:211–4.CrossRefPubMed
4.
go back to reference Desai A. Hyperkalaemia associated with inhibitors of the renin-angiotensin-aldosterone system: balancing risk and benefit. Circulation. 2008;118:1609–11.CrossRefPubMed Desai A. Hyperkalaemia associated with inhibitors of the renin-angiotensin-aldosterone system: balancing risk and benefit. Circulation. 2008;118:1609–11.CrossRefPubMed
5.
go back to reference Palmer BF. Managing hyperkalemia caused by inhibitors of the renin-angiotensin-aldosterone system. N Engl J Med. 2004;351:585–92.CrossRefPubMed Palmer BF. Managing hyperkalemia caused by inhibitors of the renin-angiotensin-aldosterone system. N Engl J Med. 2004;351:585–92.CrossRefPubMed
6.
go back to reference Einhorn LM, Zhan M, Hsu VD, Walker LD, Moen MF, Seliger SL, et al. The frequency of hyperkalemia and its significance in chronic kidney disease. Arch Intern Med. 2009;169(12):1156–62.CrossRefPubMedPubMedCentral Einhorn LM, Zhan M, Hsu VD, Walker LD, Moen MF, Seliger SL, et al. The frequency of hyperkalemia and its significance in chronic kidney disease. Arch Intern Med. 2009;169(12):1156–62.CrossRefPubMedPubMedCentral
7.
go back to reference Pitt B, Bakris G, Ruilope LM, DiCarlo L, Mukherjee R. Serum potassium and clinical outcomes in the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). Circulation. 2008;118(16):1643–50.CrossRefPubMed Pitt B, Bakris G, Ruilope LM, DiCarlo L, Mukherjee R. Serum potassium and clinical outcomes in the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). Circulation. 2008;118(16):1643–50.CrossRefPubMed
8.
go back to reference Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, et al. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011;364(1):11–21.CrossRefPubMed Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, et al. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011;364(1):11–21.CrossRefPubMed
9.
go back to reference Jain N, Kotla S, Little BB, Weideman RA, Brilakis ES, Reilly RF, et al. Predictors of hyperkalemia and death in patients with cardiac and renal disease. Am J Cardiol. 2012;109(10):1510–13.CrossRefPubMed Jain N, Kotla S, Little BB, Weideman RA, Brilakis ES, Reilly RF, et al. Predictors of hyperkalemia and death in patients with cardiac and renal disease. Am J Cardiol. 2012;109(10):1510–13.CrossRefPubMed
10.
go back to reference Svensson M, Gustafsson F, Galatius S, Hildebrandt PR, Atar D. How prevalent is hyperkalemia and renal dysfunction during treatment with spironolactone in patients with congestive heart failure? J Card Fail. 2004;10(4):297–303.CrossRefPubMed Svensson M, Gustafsson F, Galatius S, Hildebrandt PR, Atar D. How prevalent is hyperkalemia and renal dysfunction during treatment with spironolactone in patients with congestive heart failure? J Card Fail. 2004;10(4):297–303.CrossRefPubMed
11.
go back to reference Perazella MA. Drug-induced hyperkalemia: old culprits and new offenders. Am J Med. 2000;109:307–14.CrossRefPubMed Perazella MA. Drug-induced hyperkalemia: old culprits and new offenders. Am J Med. 2000;109:307–14.CrossRefPubMed
12.
go back to reference Desai AS, Swedberg K, McMurray JJ, Granger CB, Yusuf S, Young JB, et al. Incidence and predictors of hyperkalemia in patients with heart failure: an analysis of the CHARM Program. J Am Coll Cardiol. 2007;50(20):1959–66.CrossRefPubMed Desai AS, Swedberg K, McMurray JJ, Granger CB, Yusuf S, Young JB, et al. Incidence and predictors of hyperkalemia in patients with heart failure: an analysis of the CHARM Program. J Am Coll Cardiol. 2007;50(20):1959–66.CrossRefPubMed
13.
go back to reference de Denus S, Tardif JC, White M, Bourassa MG, Racine N, Levesque S, et al. Quantification of the risk and predictors of hyperkalemia in patients with left ventricular dysfunction: a retrospective analysis of the Studies of Left Ventricular Dysfunction (SOLVD) trials. Am Heart J. 2006;152(4):705–12.CrossRefPubMed de Denus S, Tardif JC, White M, Bourassa MG, Racine N, Levesque S, et al. Quantification of the risk and predictors of hyperkalemia in patients with left ventricular dysfunction: a retrospective analysis of the Studies of Left Ventricular Dysfunction (SOLVD) trials. Am Heart J. 2006;152(4):705–12.CrossRefPubMed
16.
go back to reference Lewis JD, Schinnar R, Bilker WB, Wang X, Strom BL. Validation studies of the health improvement network (THIN) database for pharmacoepidemiology research. Pharmacoepidemiol Drug Saf. 2007;16(4):393–401.CrossRefPubMed Lewis JD, Schinnar R, Bilker WB, Wang X, Strom BL. Validation studies of the health improvement network (THIN) database for pharmacoepidemiology research. Pharmacoepidemiol Drug Saf. 2007;16(4):393–401.CrossRefPubMed
17.
go back to reference Blak BT, Thompson M, Dattani H, Bourke A. Generalisability of The Health Improvement Network (THIN) database: demographics, chronic disease prevalence and mortality rates. Inform Prim Care. 2011;19(4):251–55.PubMed Blak BT, Thompson M, Dattani H, Bourke A. Generalisability of The Health Improvement Network (THIN) database: demographics, chronic disease prevalence and mortality rates. Inform Prim Care. 2011;19(4):251–55.PubMed
18.
go back to reference Ruigómez A, García Rodríguez LA, Michel A. Incidence of heart failure: a population-based study in a general practice setting. Pharmacoepidemiol Drug Saf. 2014;23:453–4. Ruigómez A, García Rodríguez LA, Michel A. Incidence of heart failure: a population-based study in a general practice setting. Pharmacoepidemiol Drug Saf. 2014;23:453–4.
19.
go back to reference McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Bohm M, Dickstein K, et al. 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. Eur J Heart Fail. 2012;14(8):803–69.CrossRefPubMed McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Bohm M, Dickstein K, et al. 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. Eur J Heart Fail. 2012;14(8):803–69.CrossRefPubMed
20.
go back to reference Yancy CW, Jessup M, Bozkurt B, Butler J, Casey Jr DE, Drazner MH, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013;128(16):e240–327.CrossRefPubMed Yancy CW, Jessup M, Bozkurt B, Butler J, Casey Jr DE, Drazner MH, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013;128(16):e240–327.CrossRefPubMed
21.
go back to reference Muzzarelli S, Maeder MT, Toggweiler S, Rickli H, Nietlispach F, Julius B, et al. Frequency and predictors of hyperkalemia in patients ≥60 years of age with heart failure undergoing intense medical therapy. Am J Cardiol. 2012;109(5):693–98.CrossRefPubMed Muzzarelli S, Maeder MT, Toggweiler S, Rickli H, Nietlispach F, Julius B, et al. Frequency and predictors of hyperkalemia in patients ≥60 years of age with heart failure undergoing intense medical therapy. Am J Cardiol. 2012;109(5):693–98.CrossRefPubMed
22.
go back to reference Pitt B, Pfeffer MA, Assmann SF, Boineau R, Anand IS, Claggett B, et al. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med. 2014;370(15):1383–92.CrossRefPubMed Pitt B, Pfeffer MA, Assmann SF, Boineau R, Anand IS, Claggett B, et al. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med. 2014;370(15):1383–92.CrossRefPubMed
23.
go back to reference Raebel MA. Hyperkalemia associated with use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Cardiovasc Ther. 2012;30:e156–66.CrossRefPubMed Raebel MA. Hyperkalemia associated with use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Cardiovasc Ther. 2012;30:e156–66.CrossRefPubMed
24.
go back to reference Sica DA, Hess M. Pharmacotherapy in congestive heart failure: aldosterone receptor antagonism: interface with hyperkalemia in heart failure. Congest Heart Fail. 2004;10:259–64.CrossRefPubMed Sica DA, Hess M. Pharmacotherapy in congestive heart failure: aldosterone receptor antagonism: interface with hyperkalemia in heart failure. Congest Heart Fail. 2004;10:259–64.CrossRefPubMed
25.
go back to reference Lachaine J, Beauchemin C, Ramos E. Use, tolerability and compliance of spironolactone in the treatment of heart failure. BMC Clin Pharmacol. 2011;11:4.CrossRefPubMedPubMedCentral Lachaine J, Beauchemin C, Ramos E. Use, tolerability and compliance of spironolactone in the treatment of heart failure. BMC Clin Pharmacol. 2011;11:4.CrossRefPubMedPubMedCentral
26.
go back to reference Hernandez AF, Mi X, Hammill BG, Hammill SC, Heidenreich PA, Masoudi FA, et al. Associations between aldosterone antagonist therapy and risks of mortality and readmission among patients with heart failure and reduced ejection fraction. JAMA. 2012;308(20):2097–107.CrossRefPubMed Hernandez AF, Mi X, Hammill BG, Hammill SC, Heidenreich PA, Masoudi FA, et al. Associations between aldosterone antagonist therapy and risks of mortality and readmission among patients with heart failure and reduced ejection fraction. JAMA. 2012;308(20):2097–107.CrossRefPubMed
27.
go back to reference Raebel MA, Ross C, Cheetham C, Petersen H, Saylor G, Smith DH, et al. Increasingly restrictive definitions of hyperkalemia outcomes in a database study: effect on incidence estimates. Pharmacoepidemiol Drug Saf. 2010;19(1):19–25.CrossRefPubMed Raebel MA, Ross C, Cheetham C, Petersen H, Saylor G, Smith DH, et al. Increasingly restrictive definitions of hyperkalemia outcomes in a database study: effect on incidence estimates. Pharmacoepidemiol Drug Saf. 2010;19(1):19–25.CrossRefPubMed
28.
go back to reference Michel A, Martín-Pérez M, Ruigómez A, García Rodríguez LA. Risk factors for hyperkalemia in a cohort of patients with newly diagnosed heart failure: a nested case–control study in UK General Practice. Eur J Heart Fail. 2015;17(2):205–13.CrossRefPubMed Michel A, Martín-Pérez M, Ruigómez A, García Rodríguez LA. Risk factors for hyperkalemia in a cohort of patients with newly diagnosed heart failure: a nested case–control study in UK General Practice. Eur J Heart Fail. 2015;17(2):205–13.CrossRefPubMed
Metadata
Title
Impact of hyperkalaemia definition on incidence assessment: implications for epidemiological research based on a large cohort study in newly diagnosed heart failure patients in primary care
Authors
Mar Martín-Pérez
Ana Ruigómez
Alexander Michel
Luis A. García Rodríguez
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Primary Care / Issue 1/2016
Electronic ISSN: 2731-4553
DOI
https://doi.org/10.1186/s12875-016-0448-5

Other articles of this Issue 1/2016

BMC Primary Care 1/2016 Go to the issue