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  Tuesday, 20 June 2023
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What is the creatininine cut off for ARNI use
There are not a lot of data in low GFR however:

eGFR <30 mL/minute/1.73 m2: Initial: Sacubitril 24 mg/valsartan 26 mg twice daily. Double the dose as tolerated every 2 to 4 weeks to the target maintenance dose of sacubitril 97 mg/valsartan 103 mg twice daily. Note: Safety and efficacy data are limited in this population, especially at eGFR <20 mL/minute/1.73 m2

Hemodialysis, intermittent (thrice weekly): Unlikely to be significantly dialyzed (valsartan and sacubitril are both highly protein bound). Recommend dosing as though the patient has an eGFR <30 mL/minute/1.73 m2. Note: Safety and efficacy data are limited in this population

Peritoneal dialysis: Unlikely to be significantly dialyzed (valsartan and sacubitril are both highly protein bound). Recommend dosing as though the patient has an eGFR <30 mL/minute/1.73 m2. Note: Safety and efficacy data are limited in this population

References:

  1. Haynes R, Judge PK, Staplin N, et al. Effects of sacubitril/valsartan versus irbesartan in patients with chronic kidney disease. Circulation. 2018;138(15):1505-1514. doi:10.1161/CIRCULATIONAHA.118.034818 [PubMed 30002098]
  2. Pontremoli R, Borghi C, Filardi PP. Renal protection in chronic heart failure: focus on sacubitril/valsartan. Eur Heart J Cardiovasc Pharmacother. 2021:pvab030. doi:10.1093/ehjcvp/pvab030 [PubMed 33822031]
  3. Expert opinion. Senior Renal Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
  4. Ayalasomayajula S, Langenickel T, Pal P, Boggarapu S, Sunkara G. Clinical pharmacokinetics of sacubitril/valsartan (LCZ696): a novel angiotensin receptor-neprilysin inhibitor. Clin Pharmacokinet. 2017;56(12):1461-1478. doi:10.1007/s40262-017-0543-3 [PubMed 28417439]
  5. Ayalasomayajula SP, Langenickel TH, Jordaan P, et al. Effect of renal function on the pharmacokinetics of LCZ696 (sacubitril/valsartan), an angiotensin receptor neprilysin inhibitor. Eur J Clin Pharmacol. 2016;72(9):1065-1073. doi:10.1007/s00228-016-2072-7 [PubMed 27230850]
  6. Lee S, Oh J, Kim H, et al. Sacubitril/valsartan in patients with heart failure with reduced ejection fraction with end-stage of renal disease. ESC Heart Fail. 2020;7(3):1125-1129. doi:10.1002/ehf2.12659 [PubMed 32153122]
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