##common.pageHeaderLogo.altText##

Review article: Biomedical intelligence

Vol. 150 No. 3940 (2020)

Patiromer and medication optimisation in heart failure with reduced ejection fraction: a Swiss perspective

Cite this as:
Swiss Med Wkly. 2020;150:w20362
Published
06.10.2020

Summary

Despite medical advances, heart failure remains a major public health issue and is associated with considerable morbidity and mortality. Suboptimal use of evidence-based therapies and lack of medication up-titration play important roles in this regard. Hyperkalaemia is a frequent and potentially harmful finding which hinders treatment optimisation in patients with heart failure. In this review, heart failure experts from two Swiss academic hospitals discuss the principles of general pharmacological therapy in heart failure with reduced ejection fraction and the different treatment options for chronic hyperkalaemia, focusing on patiromer, a recently available potassium binder. Patiromer has been accepted for reimbursement since 1 August 2020 in Switzerland, and has been shown in several clinical trials to safely reduce potassium levels over the long term, thereby allowing up-titration or maintenance of renin-angiotensin-aldosterone inhibitors in patients with chronic kidney disease, including those with heart failure. Whether this promising approach improves outcomes in patients with heart failure and reduced ejection fraction is currently under investigation.

References

  1. Savarese G, Lund LH. Global public health burden of heart failure. Card Fail Rev. 2017;3(1):7–11. doi:.https://doi.org/10.15420/cfr.2016:25:2
  2. Https://www.Obsan.Admin.Ch/en. 2015
  3. Www.Health-stat.Admin.Ch.
  4. Schmidt M, Ulrichsen SP, Pedersen L, Bøtker HE, Sørensen HT. Thirty-year trends in heart failure hospitalization and mortality rates and the prognostic impact of co-morbidity: a Danish nationwide cohort study. Eur J Heart Fail. 2016;18(5):490–9. doi:.https://doi.org/10.1002/ejhf.486
  5. Ambrosy AP, Fonarow GC, Butler J, Chioncel O, Greene SJ, Vaduganathan M, et al. The global health and economic burden of hospitalizations for heart failure: lessons learned from hospitalized heart failure registries. J Am Coll Cardiol. 2014;63(12):1123–33. doi:.https://doi.org/10.1016/j.jacc.2013.11.053
  6. Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, et al.; ESC Scientific Document Group. 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(27):2129–200. doi:.https://doi.org/10.1093/eurheartj/ehw128
  7. Maggioni AP, Anker SD, Dahlström U, Filippatos G, Ponikowski P, Zannad F, et al.; Heart Failure Association of the ESC. Are hospitalized or ambulatory patients with heart failure treated in accordance with European Society of Cardiology guidelines? Evidence from 12,440 patients of the ESC Heart Failure Long-Term Registry. Eur J Heart Fail. 2013;15(10):1173–84. doi:.https://doi.org/10.1093/eurjhf/hft134
  8. Greene SJ, Butler J, Albert NM, DeVore AD, Sharma PP, Duffy CI, et al. Medical therapy for heart failure with reduced ejection fraction: The champ-hf registry. J Am Coll Cardiol. 2018;72(4):351–66. doi:.https://doi.org/10.1016/j.jacc.2018.04.070
  9. Komajda M, Anker SD, Cowie MR, Filippatos GS, Mengelle B, Ponikowski P, et al.; QUALIFY Investigators. Physicians’ adherence to guideline-recommended medications in heart failure with reduced ejection fraction: data from the QUALIFY global survey. Eur J Heart Fail. 2016;18(5):514–22. doi:.https://doi.org/10.1002/ejhf.510
  10. Mueller C, Bally K, Buser M, Flammer AJ, Gaspoz JM, Mach F, et al. Roadmap for the treatment of heart failure patients after hospital discharge: an interdisciplinary consensus paper. Swiss Med Wkly. 2020;150:w20159. doi:.https://doi.org/10.4414/smw.2020.20159
  11. Packer M, Poole-Wilson PA, Armstrong PW, Cleland JG, Horowitz JD, Massie BM, et al.; ATLAS Study Group. Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. Circulation. 1999;100(23):2312–8. doi:.https://doi.org/10.1161/01.CIR.100.23.2312
  12. Konstam MA, Neaton JD, Dickstein K, Drexler H, Komajda M, Martinez FA, et al.; HEAAL Investigators. Effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure (HEAAL study): a randomised, double-blind trial. Lancet. 2009;374(9704):1840–8. doi:.https://doi.org/10.1016/S0140-6736(09)61913-9
  13. Ouwerkerk W, Voors AA, Anker SD, Cleland JG, Dickstein K, Filippatos G, et al. Determinants and clinical outcome of uptitration of ACE-inhibitors and beta-blockers in patients with heart failure: a prospective European study. Eur Heart J. 2017;38(24):1883–90. doi:.https://doi.org/10.1093/eurheartj/ehx026
  14. Mordi IR, Ouwerkerk W, Anker SD, Cleland JG, Dickstein K, Metra M, et al. Heart failure treatment up-titration and outcome and age: an analysis of BIOSTAT-CHF. Eur J Heart Fail. 2020. doi:.https://doi.org/10.1002/ejhf.1799
  15. Rosano GMC, Tamargo J, Kjeldsen KP, Lainscak M, Agewall S, Anker SD, 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(3):180–8. doi:.https://doi.org/10.1093/ehjcvp/pvy015
  16. McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, et al.; PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371(11):993–1004. doi:.https://doi.org/10.1056/NEJMoa1409077
  17. Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, et al.; EMPHASIS-HF Study Group. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011;364(1):11–21. doi:.https://doi.org/10.1056/NEJMoa1009492
  18. Thomsen RW, Nicolaisen SK, Hasvold P, Garcia-Sanchez R, Pedersen L, Adelborg K, et al. Elevated potassium levels in patients with congestive heart failure: Occurrence, risk factors, and clinical outcomes: A Danish population-based cohort study. J Am Heart Assoc. 2018;7(11):7. doi:.https://doi.org/10.1161/JAHA.118.008912
  19. Muzzarelli S, Maeder MT, Toggweiler S, Rickli H, Nietlispach F, Julius B, et al.; TIME-CHF Investigators. Frequency and predictors of hyperkalemia in patients ≥60 years of age with heart failure undergoing intense medical therapy. Am J Cardiol. 2012;109(5):693–8. doi:.https://doi.org/10.1016/j.amjcard.2011.10.027
  20. Vardeny O, Claggett B, Anand I, Rossignol P, Desai AS, Zannad F, et al.; Randomized Aldactone Evaluation Study (RALES) Investigators. Incidence, predictors, and outcomes related to hypo- and hyperkalemia in patients with severe heart failure treated with a mineralocorticoid receptor antagonist. Circ Heart Fail. 2014;7(4):573–9. doi:.https://doi.org/10.1161/CIRCHEARTFAILURE.114.001104
  21. Rossignol P, Dobre D, McMurray JJ, Swedberg K, Krum H, van Veldhuisen DJ, et al. Incidence, determinants, and prognostic significance of hyperkalemia and worsening renal function in patients with heart failure receiving the mineralocorticoid receptor antagonist eplerenone or placebo in addition to optimal medical therapy: results from the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF). Circ Heart Fail. 2014;7(1):51–8. doi:.https://doi.org/10.1161/CIRCHEARTFAILURE.113.000792
  22. Aldahl M, Jensen AC, Davidsen L, Eriksen MA, Møller Hansen S, Nielsen BJ, et al. Associations of serum potassium levels with mortality in chronic heart failure patients. Eur Heart J. 2017;38(38):2890–6. doi:.https://doi.org/10.1093/eurheartj/ehx460
  23. Rossignol P, Lainscak M, Crespo-Leiro MG, Laroche C, Piepoli MF, Filippatos G, et al.; Heart Failure Long-Term Registry Investigators Group. Unravelling the interplay between hyperkalaemia, renin-angiotensin-aldosterone inhibitor use and clinical outcomes. Data from 9222 chronic heart failure patients of the ESC-HFA-EORP Heart Failure Long-Term Registry. Eur J Heart Fail. 2020;22(8):1378–89. doi:.https://doi.org/10.1002/ejhf.1793
  24. Clase CM, Carrero JJ, Ellison DH, Grams ME, Hemmelgarn BR, Jardine MJ, et al.; Conference Participants. Potassium homeostasis and management of dyskalemia in kidney diseases: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2020;97(1):42–61. doi:.https://doi.org/10.1016/j.kint.2019.09.018
  25. Desai AS, Vardeny O, Claggett B, McMurray JJ, Packer M, Swedberg K, et al. Reduced risk of hyperkalemia during treatment of heart failure with mineralocorticoid receptor antagonists by use of sacubitril/valsartan compared with enalapril: A secondary analysis of the paradigm-hf trial. JAMA Cardiol. 2017;2(1):79–85. doi:.https://doi.org/10.1001/jamacardio.2016.4733
  26. McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, et al.; DAPA-HF Trial Committees and Investigators. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381(21):1995–2008. doi:.https://doi.org/10.1056/NEJMoa1911303
  27. Elkinton JR, Clark JK, Squires RD, Bluemle LW, Jr, Crosley AP, Jr. Treatment of potassium retention in anuria with cation exchange resin; a preliminary report. Am J Med Sci. 1950;220(5):547–52. doi:.https://doi.org/10.1097/00000441-195022050-00010
  28. Nasir K, Ahmad A. Treatment of hyperkalemia in patients with chronic kidney disease: a comparison of calcium polystyrene sulphonate and sodium polystyrene sulphonate. J Ayub Med Coll Abbottabad. 2014;26(4):455–8.
  29. Lepage L, Dufour AC, Doiron J, Handfield K, Desforges K, Bell R, et al. Randomized clinical trial of sodium polystyrene sulfonate for the treatment of mild hyperkalemia in ckd. Clin J Am Soc Nephrol. 2015;10(12):2136–42. doi:.https://doi.org/10.2215/CJN.03640415
  30. Harel Z, Harel S, Shah PS, Wald R, Perl J, Bell CM. Gastrointestinal adverse events with sodium polystyrene sulfonate (Kayexalate) use: a systematic review. Am J Med. 2013;126(3):264.e9–24. doi:.https://doi.org/10.1016/j.amjmed.2012.08.016
  31. Http://www.Accessdata.Fda.Gov/drugsatfda_docs/label/2011/011287s023lbl.Pdf 2020
  32. Hoy SM. Sodium zirconium cyclosilicate: A review in hyperkalaemia. Drugs. 2018;78(15):1605–13. doi:.https://doi.org/10.1007/s40265-018-0991-6
  33. Pitt B, Anker SD, Bushinsky DA, Kitzman DW, Zannad F, Huang IZ ; PEARL-HF Investigators. Evaluation of the efficacy and safety of RLY5016, a polymeric potassium binder, in a double-blind, placebo-controlled study in patients with chronic heart failure (the PEARL-HF) trial. Eur Heart J. 2011;32(7):820–8. doi:.https://doi.org/10.1093/eurheartj/ehq502
  34. Weir MR, Bakris GL, Bushinsky DA, Mayo MR, Garza D, Stasiv Y, et al.; OPAL-HK Investigators. Patiromer in patients with kidney disease and hyperkalemia receiving RAAS inhibitors. N Engl J Med. 2015;372(3):211–21. doi:.https://doi.org/10.1056/NEJMoa1410853
  35. Bakris GL, Pitt B, Weir MR, Freeman MW, Mayo MR, Garza D, et al.; AMETHYST-DN Investigators. Effect of patiromer on serum potassium level in patients with hyperkalemia and diabetic kidney disease: The amethyst-dn randomized clinical trial. JAMA. 2015;314(2):151–61. doi:.https://doi.org/10.1001/jama.2015.7446
  36. Agarwal R, Rossignol P, Romero A, Garza D, Mayo MR, Warren S, et al. Patiromer versus placebo to enable spironolactone use in patients with resistant hypertension and chronic kidney disease (AMBER): a phase 2, randomised, double-blind, placebo-controlled trial. Lancet. 2019;394(10208):1540–50. doi:.https://doi.org/10.1016/S0140-6736(19)32135-X
  37. Pitt B, Bakris GL, Weir MR, Freeman MW, Lainscak M, Mayo MR, et al. Long-term effects of patiromer for hyperkalaemia treatment in patients with mild heart failure and diabetic nephropathy on angiotensin-converting enzymes/angiotensin receptor blockers: results from AMETHYST-DN. ESC Heart Fail. 2018;5(4):592–602. doi:.https://doi.org/10.1002/ehf2.12292
  38. Pitt B, Bakris GL, Bushinsky DA, Garza D, Mayo MR, Stasiv Y, et al. Effect of patiromer on reducing serum potassium and preventing recurrent hyperkalaemia in patients with heart failure and chronic kidney disease on RAAS inhibitors. Eur J Heart Fail. 2015;17(10):1057–65. doi:.https://doi.org/10.1002/ejhf.402
  39. Rossignol P, Williams B, Mayo MR, Warren S, Arthur S, Ackourey G, et al. Patiromer versus placebo to enable spironolactone use in patients with resistant hypertension and chronic kidney disease (AMBER): results in the pre-specified subgroup with heart failure. Eur J Heart Fail. 2020;22(8):1462–71. doi:.https://doi.org/10.1002/ejhf.1860