Some clinical dilemmas in medication with inhibitors of the renin-angiotensin-aldosterone system in patients with heart failure
DOI:
https://doi.org/10.52692/1857-0011.2024.1-78.19Keywords:
inhibitors of the renin-angiotensin-aldosterone system, heart failure, hyperkaliemiaAbstract
Use of renin-angiotensin-aldosterone system inhibitors in patients with heart failure and reduced ejection fraction is associated with functional improvement, an increase in perceived quality of life, a reduction in the probability of cardiovascular death, and a decrease in the number of hospitalizations. Some of these drugs are also efficacious in patients with chronic kidney disease and albuminuria as well as in patients with resistant hypertension. Despite their numerous benefits, renin-angiotensin-aldosterone system inhibitors are associated with an increase in incidence of hyperkalemia, especially in patients with concomitant chronic kidney disease. Hyperkalemia is a common electrolyte disorder that is defined as an elevation in plasma concentrations of potassium above 5 mEq/L. It has been related to rehospitalizations, malignant arrhythmias, and an increase in mortality. On the other hand, optimized treatment with renin-angiotensinaldosterone system inhibitors requires progressive dose increases which can in turn entail a greater probability of hyperkalemia.
References
Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37:2129---200, doi:10.1093/ eurheartj/ehw128.
Wang K, Hu J, Luo T, et al. Effects of angiotensin- converting enzyme inhibitors and angiotensin II receptor blockers on all-cause mortality and renal outcomes in patients with diabetes and albuminuria: a systematic review and meta-analysis. Kidney Blood Press Res. 2018;43:768---79, doi:10.1159/000489913.
Acelajado MC, Hughes ZH, Oparil S, Calhoun DA. Treatment of resistant and refractory hypertension. Circ Res. 2019;124:1061---70, doi:10.1161/circresaha.118.312156.
Einhorn LM, Zhan M, Hsu VD, et al. The frequency of hyperkalemia and its significance in chronic kidney disease. Arch Intern Med. 2009;169:1156---62, doi:10.1001/archinternmed.2009.132.
Hoppe LK, Muhlack DC, Koenig W, et al. Association of abnormal serum potassium levels with arrhythmias and cardiovascular mortality: a systematic review and meta- analysis of observational studies. Cardiovasc Drugs Ther. 2018;32:197---212, doi:10.1007/s10557-018-6783-0.
Raebel MA. Hyperkalemia associated with use of angiotensin-converting enzyme inhibitors and angiotensin 239 L. Almenar Bonet and Á. González-Franco receptor blockers. Cardiovasc Ther. 2012;30:e156---166, doi:10.1111/j.1755-5922.2010.00258.x.
Rosano GMC, Tamargo J, Kjeldsen KP, Lewis BS, et al. (2018) Expert consensus document on the management of hyperkalaemia in patients with cardiovascular disease treated with renin angiotensin aldosterone system inhibitors: coordinated by the Working Group on Cardiovascular Pharmacotherapy of the European Society of Cardiology. Eur Heart J Cardiovasc Pharmacother 4:180–188.
Alfonzo A, Harrison A, Baines R, et. All. UK Kidney Association (2020) Renal association clinical practice guidelines: treatment of acute hyperkalaemia in adults.
American Heart Association (2005) Guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Part 10.1: life-threatening electrolyte abnormalities. Circulation 112:IV121– IV125.
Howlett JG, Chan M, Ezekowitz JA, et. al. Canadian Cardiovascular Society Heart Failure Guidelines Panels (2016) The Canadian Cardiovascular Society heart failure companion: bridging guidelines to your practice. Can J Cardiol 32:296–310.
National Kidney Foundation (2014) Clinical update on hyperkalemia.
Bianchi S, Aucella F, De Nicola L, et. al. (2019) Management of hyperkalemia in patients with kidney disease: a position paper endorsed by the Italian Society of Nephrology. J Nephrol 32:499–516.
Nilsson E, Gasparini A, et. al. (2017) Incidence and determinants of hyperkalemia and hypokalemia in a large healthcare system. Int J Cardiol 245:277–284.
Rossignol P, Lainscak M, Crespo-Leiro MG, et. al. Heart Failure Long-Term Registry Investigators Group (2020) Unravelling the interplay between hyperkalaemia, renin-angiotensin-aldosterone inhibitor use and clinical outcomes. Eur J Heart Fail 22:1378–1389.
Einhorn LM, Zhan M, Hsu VD, et. al. (2009) The frequency of hyperkalemia and its signifcance in chronic kidney disease. Arch Intern Med 169:1156–1162.
Sarafdis PA, Blacklock R, Wood E, et.all. (2012) Prevalence and factors associated with hyperkalemia in predialysis patients followed in a low-clearance clinic. Clin J Am Soc Nephrol 7:1234–1241.
Luo X, Xu J, Zhou S, Xue C, et. al. (2023) Infuence of SGLT2i and RAASi and their combination on risk of hyperkalemia in DKD: a network meta-analysis. Clin J Am Soc Nephrol.
Neuen BL, Oshima M, Perkovic V, et. All. (2021) Efects of canaglifozin on serum potassium in people with diabetes and chronic kidney disease: the CREDENCE trial. Eur Heart J 42:4891–4901.
Hsu TW, Liu JS, Hung SC, et al. Renoprotective effect of reninangiotensin-aldosterone system blockade in patients with predialysis advanced chronic kidney disease, hypertension, and anemia. JAMA Intern Med. 2014;174:347–354.
Dzau VJ, Antman EM, Black HR, et al. The cardiovascular disease continuum validated: clinical evidence of improved patient outcomes: part I: pathophysiology and clinical trial evidence (risk factors through stable coronary artery disease). Circulation. 2006;114:2850–2870.
Kovesdy CP. Epidemiology of hyperkalemia: an update. Kidney Int Suppl. 2016;6:3–6.
Ferrario CM. New physiological concepts of the renin-angiotensin system from the investigation of precursors and products of angiotensin I metabolism. Hypertension. 2010;55:445–452.
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;46:845–849.
Bozkurt B, Agoston MD, 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;41:211–214.
Pitt B, Zannad F, Remme WJ, et al., for the Randomized Aldactone Evaluation Study Investigators. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med. 1999;341:709–717.
Zannad F, McMurray JJ, Krum H, et al., for the EMPHASIS-HF Study Group. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011;364:11–21.
Epstein M, Reaven NL, Funk SE, et al. Evaluation of the treatment gap between clinical guidelines and the utilization of renin-angiotensin-aldosterone system inhibitors. Am J Manag Care. 2015;21(11 suppl): S212– S220. 5220.
Rosano GMC, Tamargo J, Kjeldsen KP, et al. Expert consensus document on the management of hyperkalaemia in patients with cardiovascular disease treated with renin angiotensin aldosterone system inhibitors: coordinated by the Working Group on Cardiovascular Pharmacotherapy of the European Society of Cardiology. Eur Heart J Cardiovasc Pharmacother. 2018;4:180---8, doi:10.1093/ehjcvp/pvy015.
Alvo M, Warnock DG. Hyperkalemia. West J Med. 1984;141:666---71.
Perazella MA, Mahnensmith RL. Hyperkalemia in the elderly: drugs exacerbate impaired potassium homeostasis. J Gen Intern Med. 1997;12:646---56, doi:10.1046/j.1525-1497.1997.07128.x.
Crespo-Leiro MG, Anker SD, Maggioni AP, et al. European Society of Cardiology Heart Failure Long-Term Registry (ESC-HF-LT): 1-year follow-up outcomes and differences across regions. Eur J Heart Fail. 2016;18:613---25, doi:10.1002/ejhf.566.
Rosano GM, Spoletini I, Vitale C, Agewall S. Hyperkalemia and renin-angiotensin-aldosterone system inhibitors dose therapy in heart failure with reduced ejection fraction. Card Fail Rev. 2019;5:130–2.
Renal Association. Clinical Practice Guideline. Treatment of acute hyperkalaemia in adults. 2020.
Ponikowski P, Voors AA, Anker SD, et al.; ESC Scientific Document Group. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37:2129–200.
Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2020 clinical practice guideline for diabetes management in chronic kidney disease. Kidney Int. 2020;98:S1–S115.
Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group. KDIGO 2021 clinical practice guideline for the management of blood pressure in chronic kidney disease. Kidney Int. 2021;99:S1–S87.
Ezekowitz JA, O’Meara E, McDonald MA, et al. 2017 comprehensive update of the Canadian Cardiovascular Society guidelines for the management of heart failure. Can J Cardiol. 2017;33:1342–433.
House AA, Wanner C, Sarnak MJ, et al. Heart failure in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) controversies conference. Kidney Int. 2019;95:1304–17.
Wang AY. Optimally managing hyperkalemia in patients with cardiorenal syndrome. Nephrol Dial Transplant. 2019;34:iii36–44.
Epstein M, Reaven NL, Funk SE, et. al. Evaluation of the treatment gap between clinical guidelines and the utilization of renin-angiotensin-aldosterone system inhibitors. Am J Manag Care. 2015;21:S212–20.
Trevisan M, de Deco P, Xu H, Evans et al. Incidence, predictors and clinical management of hyperkalaemia in new users of mineralocorticoid receptor antagonists. Eur J Heart Fail. 2018;20:1217–26.
McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur J Heart Fail. 2022;24:4–131.
Renal Association. Clinical Practice Guideline. Treatment of acute hyperkalaemia in adults. 2020.
Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2020 clinical practice guideline for diabetes management in chronic kidney disease. Kidney Int. 2020;98:S1–S115.
Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group. KDIGO 2021 clinical practice guideline for the management of blood pressure in chronic kidney disease. Kidney Int. 2021;99:S1–S87.
Lisi F, Parisi G, Gioia MI, et al. Mineralcorticoid receptor antagonist withdrawal for hyperkalemia and mortality in patients with heartfailure. Cardiorenal Med. 2020;10:145---53, doi:10.1159/000505286.
Molnar MZ, Kalantar-Zadeh K, Lott EH, et al. Angiotensin-converting enzyme inhibitor, angiotensin receptor blocker use, and mortality in patients with chronic kidney disease. J Am Coll Cardiol. 2014;63:650---8, doi:10.1016/j.jacc.2013.10.050.
Darden D, Drazner MH, Mullens W, Dupont M, Tang WHW, Grodin JL. Implications of renin-angiotensin- system blocker discontinuation in acute decompensated heart failure with systolic dysfunction. Clin Cardiol. 2019;42:1010---8, doi:10.1002/clc.23260.
Esteban-Fernández A, Díez-Villanueva P, Vicent L, et al. Sacubitril/Valsartan is useful and safe in elderly
people with heart failure and reduced ejection fraction. Data from a real-word cohort. Rev Esp Geriatr Gerontol. 2020;55:65---9, doi:10.1016/j.regg.2019.10.002.
Núnez ˜ J, Bayes-Genis A, Zannad F, Rossignol P, et al. Long-term potassium monitoring and dynamics in heart failure and risk of mortality. Circulation. 2018;137:1320--- 30, doi:10.1161/circulationaha.117.030576.
Rosano GMC, Tamargo J, Kjeldsen KP, et al. Expert consensus document on the management of hyperkalaemia in patients with cardiovascular disease treated with renin angiotensin aldosterone system inhibitors: coordinated by the Working Group on Cardiovascular Pharmacotherapy of the European Society of Cardiology. Eur Heart J Cardiovasc Pharmacother. 2018;4:180---8, doi:10.1093/ ehjcvp/pvy015.
Pitt B, Bushinsky DA, Kitzman DW, et al.; Patiromer-204 Investigators. Evaluation of an individualized dose titration regimen of patiromer to prevent hyperkalaemia in patients with heart failure and chronic kidney disease. ESC Heart Fail. 2018;5: 257–66.
Packham DK, Rasmussen HS, Lavin PT, et al. Sodium zirconium cyclosilicate in hyperkalemia. N Engl J Med. 2015;372: 222–31.
Li L, Harrison SD, Cope MJ, Park C, et al. (2016) Mechanism of action and pharmacology of patiromer, a nonabsorbed cross-linked polymer that lowers serum potassium concentration in patients with hyperkalemia. J Cardiovasc Pharmacol Ther 21:456–465.
European Medicines Agency (2022) Lokelma (soidum zirconium cyclosilicate): summary of product characteristics.https://www.ema.europa.eu/en/documents/product-information/lokelma-eparproductinformation_en.pdf.
Meaney CJ, Beccari MV, Yang Y, Zhao J (2017) Systematic review and meta-analysis of patiromer and sodium zirconium cyclosilicate: a new armamentarium for the treatment of hyperkalemia. Pharmacotherapy 37:401–411.
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