Skip to main content
SpringerLink
Log in

Incidence of risk factors for developing hyperkalemia when using ACE inhibitors in cardiovascular diseases

  • Research Article
  • Published:
Pharmacy World & Science Aims and scope Submit manuscript

Abstract

Study objective To determine the incidence of and the risk factors associated with hyperkalemia, induced by ACEI–drug interactions among cardiac patients. Setting Five medical and cardiology wards of a tertiary care center in Malaysia. Subjects Five hundred cardiac inpatients, who received ACEIs concomitantly with other interacting drugs. Method This was a prospective cohort study of 500 patients with cardiovascular diseases admitted to Penang Hospital between January to August 2006, who received ACEIs concomitantly with other interacting drugs. ACEI–drug interactions of clinical significance were identified using available drug information resources. Drug Interaction Probability Scale (DIPS) was used to assess the causality of association between ACEI–drug interactions and the adverse outcome (hyperkalemia). Main outcome measure Hyperkalemia as an adverse clinical outcome of the interaction was identified from laboratory investigations. Results Of the 489 patients included in the analysis, 48 (9.8%) had hyperkalemia thought to be associated with ACEI–drug interactions. Univariate analysis using binary logistic regression revealed that advanced age (60 years or more), and taking more than 15 medications were independent risk factors significantly associated with hyperkalemia. However, current and previous smoking history appeared to be a protective factor. Risk factors identified as predictors of hyperkalemia secondary to ACEI–drug interactions by multi-logistic regression were: advanced age (adjusted OR 2.3, CI 1.07–5.01); renal disease (adjusted OR 4.7, CI 2.37–9.39); hepatic disease (adjusted OR 5.2, CI 1.08–25.03); taking 15–20 medications (adjusted OR 4.4, CI 2.08–9.19); and taking 21–26 medications (adjusted OR 9.0, CI 1.64–49.74). Conclusion Cardiac patients receiving ACEIs concomitantly with potentially interacting drugs are at high risk of experiencing hyperkalemia. Old age, renal disease, hepatic disease, and receiving large number of medications are factors that may significantly increase their vulnerability towards this adverse outcome; thus, frequent monitoring is advocated.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Sica DA. Angiotensin-converting enzyme inhibitors side effects: physiologic and non-physiologic considerations. J Clin Hypertens. 2004;6(7):410–6. doi:10.1111/j.1524-6175.2004.02866.x.

    Article  CAS  Google Scholar 

  2. Perazella MA, Mahnensmith RL. Hyperkalemia in the elderly drugs exacerbate impaired potassium homeostasis. J Gen Intern Med. 1997;12(10):646–56. doi:10.1046/j.1525-1497.1997.07128.x.

    Article  PubMed  CAS  Google Scholar 

  3. Bakris GL, Weir MR. Angiotensin-converting enzyme inhibitor-associated elevations in serum creatinine: is this a cause for concern? Arch Intern Med. 2000;160(5):685–93. doi:10.1001/archinte.160.5.685.

    Article  PubMed  CAS  Google Scholar 

  4. Cruz CS, Cruz AA, Marcilio de Souza CA. Hyperkalaemia in congestive heart failure patients using ACE inhibitors and spironolactone. Nephrol Dial Transplant. 2003;18(9):1814–9. doi:10.1093/ndt/gfg295.

    Article  PubMed  CAS  Google Scholar 

  5. RALES Investigators. Effectiveness of spironolactone added to an angiotensin-converting enzyme inhibitor and a loop diuretic for severe chronic congestive heart failure (the randomized aldactone evaluation study, RALES). Am J Cardiol. 1996;78(6):902–7.

    Google Scholar 

  6. Anton C, Cox AR, Watson RDS, Ferner RE. The safety of spironolactone treatment in patients with heart failure. J Clin Pharm Ther. 2003;28(4):285–7. doi:10.1046/j.1365-2710.2003.00491.x.

    Article  PubMed  CAS  Google Scholar 

  7. Palmer B. Managing hyperkalemia caused by inhibitors of the renin–angiotensin–aldosterone system. N Engl J Med. 2004;351(6):585–92. doi:10.1056/NEJMra035279.

    Article  PubMed  CAS  Google Scholar 

  8. Saito M, Takada M, Hirooka K, Isobe F, Yasumura Y. Serum concentration of potassium in chronic heart failure patients administered spironolactone plus furosemide and either enalapril maleate, losartan potassium or candesartan cilexetil. J Clin Pharm Ther. 2005;30(6):603–10. doi:10.1111/j.1365-2710.2005.00694.x.

    Article  PubMed  CAS  Google Scholar 

  9. 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(6):543–51. doi:10.1056/NEJMoa040135.

    Article  PubMed  CAS  Google Scholar 

  10. Wrenger E, Muller R, Moesenthin M, Welte T, Frolich JC, Neumann KH. Interaction of spironolactone with ACE inhibitors or angiotensin receptor blockers: analysis of 44 cases. BMJ. 2003;327(7407):147–9. doi:10.1136/bmj.327.7407.147.

    Article  PubMed  CAS  Google Scholar 

  11. 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. doi:10.1016/j.cardfail.2003.10.012.

    Article  PubMed  CAS  Google Scholar 

  12. Ramadan FH, Masoodi N, El-Solh AA. Clinical factors associated with hyperkalemia in patients with congestive heart failure. J Clin Pharm Ther. 2005;30(7):233–9. doi:10.1111/j.1365-2710.2005.00638.x.

    Article  PubMed  CAS  Google Scholar 

  13. Chan LN, Horn JR. Management of metabolic drug interactions. In: Carter BL, Lake KD, Raebel MA, Bertch KE, Israel MK, Jermain DM, et al., editors. Pharmacotherapy Self-Assessment Program (PSAP). 3rd ed. Module 8. USA: ACCP; 2000. p. 102.

  14. Hansten PD, Horn JR. Managing clinically important drug interactions. USA: Wolter Kluwer Health, Inc; 2005.

    Google Scholar 

  15. Lacy CF, Armstrong LL, Goldman MP, Lance LL. Drug information handbook international. 14th ed. Hudson, Ohlo: Lexi-Comp Inc; 2006.

    Google Scholar 

  16. British National Formulary (BNF). Britain, R. P. S. O. G. 54th ed. London: BMJ Publishing Group Ltd and RPS Publishing; 2007.

    Google Scholar 

  17. Field A. Discovering statistics using SPSS. London: SAGE Publications Ltd; 2005. p. 208.

    Google Scholar 

  18. Hosmer DW, Taber S, Lemeshow S. The importance of assessing the fit of logistic regression models: a case study. Am J Public Health. 1991;81(12):1630–5.

    Article  PubMed  CAS  Google Scholar 

  19. Obialo CI, Ofili EO, Mirza T. Hyperkalemia in congestive heart failure patients aged 63 to 85 years with subclinical renal disease. Am J Cardiol. 2002;90:663–5. doi:10.1016/S0002-9149(02)02581-X.

    Article  PubMed  CAS  Google Scholar 

  20. Tamirisa KP, Aaronson KD, Koelling TM. Spironolactone-induced renal insufficiency and hyperkalemia in patients with heart failure. Am Heart J. 2004;148:971–8. doi:10.1016/j.ahj.2004.10.005.

    Article  PubMed  CAS  Google Scholar 

  21. Reardon LC, Macpherson DS. Hyperkalemia in outpatients using angiotensin-converting enzyme inhibitors: how much should we worry? Arch Intern Med. 1998;158:26–32. doi:10.1001/archinte.158.1.26.

    Article  PubMed  CAS  Google Scholar 

  22. Shah KB, Rao K, Sawyer R, Gottlieb SS. The adequacy of laboratory monitoring in patients treated with spironolactone for congestive heart failure. J Am Coll Cardiol. 2005;46:845–9. doi:10.1016/j.jacc.2005.06.010.

    Article  PubMed  CAS  Google Scholar 

  23. Schepkens H, Vanholder R, Billiouw J, Lameire N. Life-threatening hyperkalemia during combined therapy with angiotensin-converting enzyme inhibitors and spironolactone: an analysis of 25 cases. Am J Med. 2001;110(6):438–41. doi:10.1016/S0002-9343(01)00642-8.

    Article  PubMed  CAS  Google Scholar 

  24. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, et al. The Effect of spironolactone on morbidity and mortality in patients with severe heart failure (RALES). N Engl J Med. 1999;341:709–17. doi:10.1056/NEJM199909023411001.

    Article  PubMed  CAS  Google Scholar 

  25. Raebel MA, McClure DL, Chan KA. Laboratory evaluation of potassium and creatinine among ambulatory patients prescribed spironolactone: are we monitoring for hyperkalemia? Ann Pharmacother. 2007;41(2):193–200. doi:10.1345/aph.1H520.

    Article  PubMed  CAS  Google Scholar 

  26. Stevens M, Dunlay R. Hyperkalemia in hospitalized patients. Int Urol Nephrol. 2000;32(2):177–80. doi:10.1023/A:1007135517950.

    Article  PubMed  CAS  Google Scholar 

  27. De Denus S, Tardif J, 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. doi:10.1016/j.ahj.2006.05.030.

    Article  PubMed  CAS  Google Scholar 

  28. Horn H. Hyperkalemia due to drug interactions. Pharm Times. 2004; www.hanstenandhorn.com. Accessed 28 Aug 2008.

  29. Mangoni AA, Jackson SHD. Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications. Br J Clin Pharmacol. 2003;57(1):6–14. doi:10.1046/j.1365-2125.2003.02007.x.

    Article  CAS  Google Scholar 

  30. Bates DW, Miller EB, Cullen DJ, Burdick L, Williams L, Laird N, et al. Patient risk factors for adverse drug events in hospitalized patients. Arch Intern Med. 1999;159(21):2553–60. doi:10.1001/archinte.159.21.2553.

    Article  PubMed  CAS  Google Scholar 

  31. Bente G, Stig EA, Kim D. Drug-drug interactions among recently hospitalised patients—frequent but mostly clinically insignificant. Eur J Clin Pharmacol. 2005;61(9):675–81. doi:10.1007/s00228-005-0978-6.

    Article  Google Scholar 

  32. Ramsay L, Tucker GT. Drugs and the elderly. BMJ. 1981;282:125–7.

    Article  PubMed  CAS  Google Scholar 

  33. Butler JV, McAvoy H, McEnroy D, Mulkerrin EC. Spironolactone therapy in older patients—the impact of renal dysfunction. Arch Gerontol Geriatr. 2002;35(1):45–9. doi:10.1016/S0167-4943(01)00214-X.

    Article  PubMed  CAS  Google Scholar 

  34. Hay E, Derazon H, Bukish N, Katz L, Kruglyakov I, Armoni M. Fatal hyperkalemia related to combined therapy with a COX-2 inhibitor, ACE inhibitor and potassium rich diet. J Emerg Med. 2002;22:349–52. doi:10.1016/S0736-4679(02)00434-1.

    Article  PubMed  Google Scholar 

  35. Wannamethee SG, Lever AF, Shaper AG, Whincup PH. Serum potassium, cigarette smoking, and mortality in middle-aged Men. Am J Epidemiol. 1997;145(7):598–606.

    PubMed  CAS  Google Scholar 

  36. Orth SR. Smoking and the kidney. J Am Soc Nephrol. 2002;13(6):1663–72. doi:10.1097/01.ASN.0000018401.82863.FD.

    Article  PubMed  CAS  Google Scholar 

  37. Paice B, Gray JM, McBride D, Donnelly T, Lawson DH. Hyperkalaemia in patients in hospital. BMJ. 1983;286(6372):1189–92.

    Article  PubMed  CAS  Google Scholar 

  38. Hu Y, Carpenter JP, Cheung AT. Life-threatening hyperkalemia: a complication of spironolactone for heart failure in a patient with renal insufficiency. Anesth Analg. 2002;95(1):39–41. doi:10.1097/00000539-200207000-00006.

    Article  PubMed  Google Scholar 

  39. Weiner D, Wingo C. Hyperkalemia: a potential silent killer. J Am Soc Nephrol. 1998;9:1535–43.

    PubMed  CAS  Google Scholar 

  40. Gurwitz JH, Field TS, Judge J, Rochon P, Harrold LR, Cadoret C, et al. The incidence of adverse drug events in two large academic long-term care facilities. Am J Med. 2005;118(3):251–8. doi:10.1016/j.amjmed.2004.09.018.

    Article  PubMed  Google Scholar 

  41. Heininger-Rothbucher D, Bischinger S, Ulmer H, Pechlaner C, Speer G, Wiedermann CJ. Incidence and risk of potential adverse drug interactions in the emergency room. Resuscitation. 2001;49(3):283–8. doi:10.1016/S0300-9572(00)00363-4.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank the Ministry of Health, Khartoum State, Sudan for awarding the scholarship for this research. We also thank the Khartoum Medical Insurance Services Corporation, Khartoum State and the staff of pharmacy department, medical and cardiology wards at Penang Hospital, Malaysia for their cooperation.

Funding

None.

Conflicts of interest

None to declare.

Author information

Authors and Affiliations

  1. Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800, Penang, Malaysia

    Omalhassan Amir, Yahaya Hassan, Azmi Sarriff, Ahmed Awaisu & Noorizan Abd. Aziz

  2. Department of Cardiology, Penang General Hospital, 10990, Penang, Malaysia

    Omar Ismail

Authors
  1. Omalhassan Amir
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yahaya Hassan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Azmi Sarriff
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ahmed Awaisu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Noorizan Abd. Aziz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Omar Ismail
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yahaya Hassan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Amir, O., Hassan, Y., Sarriff, A. et al. Incidence of risk factors for developing hyperkalemia when using ACE inhibitors in cardiovascular diseases. Pharm World Sci 31, 387–393 (2009). https://doi.org/10.1007/s11096-009-9288-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11096-009-9288-x

Keywords

Search

Navigation