Skip to main content
SpringerLink
Log in

Sacubitril/Valsartan in Dialysis Patients: Update on Current Perspectives

  • Review Article
  • Published:
Cardiovascular Drugs and Therapy Aims and scope Submit manuscript

Abstract

Sacubitril/Valsartan is a combination of neprilysin inhibitor and angiotensin II receptor blocker that proved its own efficacy and safety in heart failure patients to ameliorate cardiovascular morbidity and mortality compared to angiotensin II-converting enzyme inhibitors alone. However, end-stage renal disease patients have not been included in the randomized controlled trials, so the beneficial effects as well as the risk profile of this association remain still undefined in these patients. Only observational studies on this drug association have been carried out in end-stage renal disease patients investigating mostly biohumoral or echocardiographic markers. Therefore, its application is still controversial and not free of complications due to the potential risk of hypotension and hyperkaliemia. The efficacy to improve biohumoral markers and cardiac function in dialysis patients and the potential application especially in those patients with severe and resistant hypertension and/or left ventricular dysfunction could be crucial in end-stage renal disease patients. Ongoing long-term randomized controlled trials should thoroughly define the effective benefits and/or adverse effects in patients on substitutive treatment.

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

Fig. 1

Similar content being viewed by others

Data availability

Not requested.

Code Availability

No software application requested.

References

  1. Coresh J, Selvin E, Stevens LA, et al. Prevalence of chronic kidney disease in the United States. JAMA. 2007;298:2038–204.

    Article  CAS  PubMed  Google Scholar 

  2. Hill NR, Fatoba ST, Oke JL, Hirst JA, O’Callaghan CA, Lasserson DS, Hobbs FD. Global prevalence of chronic kidney disease—a systematic review and meta-analysis. PLoS One. 2016;11:e0158765.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Weber KT. Aldosterone in congestive heart failure. N Engl J Med. 2001;345:1689–97.

    Article  CAS  PubMed  Google Scholar 

  4. Ruiz S, Pergola PE, Zager RA, Vaziri ND. Targeting the transcription factor Nrf2 to ameliorate oxidative stress and inflammation in chronic kidney disease. Kidney Int. 2013;83:1029–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. McCullough PA, Kellum JA, Haase M, et al. Pathophysiology of the cardiorenal syndromes: executive summary from the eleventh consensus conference of the Acute Dialysis Quality Initiative (ADQI). Contrib Nephrol. 2013;182:82–98.

    Article  PubMed  Google Scholar 

  6. Spatola L, Rivera RF, Migliore F, Bilato C, Mugnai G. Cardiovascular implantable electronic devices in hemodialysis patients: an updated review. J Cardiovasc Med (Hagerstown). 2021;22(12):867–73.

    PubMed  Google Scholar 

  7. The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med. 1991;325:293–302.

    Article  Google Scholar 

  8. CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med. 1987;316(23):1429–35. PMID: 2883575

    Article  Google Scholar 

  9. Cohn JN, Tognoni G. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med. 2001;345:1667–75.

    Article  CAS  PubMed  Google Scholar 

  10. McMurray JJ, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993–1004.

    Article  PubMed  Google Scholar 

  11. Velazquez EJ, Morrow DA, DeVore AD, et al. Angiotensin-neprilysin inhibition in acute decompensated heart failure. N Engl J Med. 2019;380:539–48.

    Article  CAS  PubMed  Google Scholar 

  12. Solomon SD, McMurray JJV, Anand IS, et al. Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction. N Engl J Med. 2019;381(17):1609–20.

    Article  CAS  PubMed  Google Scholar 

  13. Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA Focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American college of cardiology/American heart association task force on clinical practice guidelines and the heart failure society of America. Circulation. 2017;136(6):e137-e161. https://doi.org/10.1161/CIR.0000000000000509.

  14. ESC Scientific Document Group, McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). With the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2022;24(1):4–131. PMID: 35083827

    Article  Google Scholar 

  15. Fu S, Ping P, Wang F, Luo L. Synthesis, secretion, function, metabolism and application of natriuretic peptides in heart failure. J. Biol. Eng. 2018;12:2.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Bayes-Genis A, Barallat J, Richards AM. A test in context: neprilysin: function, inhibition, and biomarker. J Am Coll Cardiol. 2016;68:639–53.

    Article  CAS  PubMed  Google Scholar 

  17. Singh JSS, Burrell LM, Cherif M, Squire IB, Clark AL, Lang CC. Sacubitril/valsartan: beyond natriuretic peptides. Heart. 2017;103:1569–77.

    Article  CAS  PubMed  Google Scholar 

  18. Packer M, Califf RM, Konstam MA, Krum H, McMurray JJ, Rouleau JL, Swedberg K. Comparison of omapatrilat and enalapril in patients with chronic heart failure: the omapatrilat versus enalapril randomized trial of utility in reducing events (OVERTURE). Circulation. 2002;106:920–6.

    Article  CAS  PubMed  Google Scholar 

  19. Kostis JB, Packer M, Black HR, Schmieder R, Henry D, Levy E. Omapatrilat and enalapril in patients with hypertension: the Omapatrilat Cardiovascular Treatment vs. Enalapril (OCTAVE) trial. Am. J. Hypertens. 2004;17:103–11.

    Article  CAS  PubMed  Google Scholar 

  20. Haynes R, Zhu D, Judge PK, Herrington WG, Kalra PA, Baigent C. Chronic kidney disease, heart failure and neprilysin inhibition. Nephrol. Dial. Transplant. 2020;35:558–64.

    Article  CAS  PubMed  Google Scholar 

  21. Ushijima K, Ando H, Arakawa Y, Aizawa K, Suzuki C, Shimada K, Tsuruoka SI, Fujimura A. Prevention against renal damage in rats with subtotal nephrectomy by sacubitril/valsartan (LCZ696), a dual-acting angiotensin receptor-neprilysin inhibitor. Pharmacol Res Perspect. 2017;5:e00336.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Suematsu Y, Jing W, Nunes A, Kashyap ML, Khazaeli M, Vaziri ND, Moradi H. LCZ696 (Sacubitril/Valsartan), an angiotensin-receptor neprilysin inhibitor, attenuates cardiac hypertrophy, fibrosis, and vasculopathy in a rat model of chronic kidney disease. J Card Fail. 2018;24:266–75.

    Article  CAS  PubMed  Google Scholar 

  23. Wang BH, Von Lueder TG, Kompa AR, Li H, Webb R, Jordaan P, Atar D, Krum H. Combined angiotensin receptor blockade and neprilysin inhibition attenuates angiotensin-II mediated renal cellular collagen synthesis. Int J Cardiol. 2015;186:104–5.

    Article  PubMed  Google Scholar 

  24. Haynes R, Judge PK, Staplin N, Landray MJ, Baigent C. Results of a randomized multicentre pilot study of sacubitril/valsartan versus irbesartan in patients with CKD: United Kingdom heart and renal protection (UK HARP)-III trial. J Am Soc Nephrol. 2017;28:B5.

    Google Scholar 

  25. Cheung AK, Chang TI, Cushman WC, Furth SL, Hou FF, Ix JH, Knoll GA, Muntner P, Pecoits-Filho R, Sarnak MJ, Tobe SW, Tomson CRV, Lytvyn L, Craig JC, Tunnicliffe DJ, Howell M, Tonelli M, Cheung M, Earley A, Mann JFE. Executive summary of the KDIGO 2021 clinical practice guideline for the management of blood pressure in chronic kidney disease. Kidney Int. 2021;99:559–69.

    Article  PubMed  Google Scholar 

  26. Chang HY, Feng AN, Fong MC, Hsueh CW, Lai WT, Huang KC, Chong E, Chen CN, Chang HC, Yin WH. Sacubitril/valsartan in heart failure with reduced ejection fraction patients: real world experience on advanced chronic kidney disease, hypotension, and dose escalation. J Cardiol. 2019;74:372–80.

    Article  PubMed  Google Scholar 

  27. Niu C-Y, Yang S-F, Ou S-M, Wu C-H, Huang P-H, Hung C-L, Lin C-C, Li S-Y. Sacubitril/Valsartan in patients with heart failure and concomitant end-stage kidney disease. J Am Heart Assoc. 2022;11(18):e026407. Epub 2022 Sep 5

    Article  PubMed  PubMed Central  Google Scholar 

  28. Lee S, Oh J, Kim H, Ha J, Chun KH, Lee CJ, Park S, Lee SH, Kang SM. Sacubitril/valsartan in patients with heart failure with reduced ejection fraction with end-stage of renal disease. ESC Heart Fail. 2020;7:1125–9.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Heyse A, Manhaeghe L, Mahieu E, Vanfraechem C, Van Durme F. Sacubitril/valsartan in heart failure and end-stage renal insufficiency. ESC Heart Fail. 2019;6(6):1331-1333.  Epub 2019 Oct 30.PMID: 31668014.

  30. Hsiao FC, Lin CP, Yu CC, Tung YC, Chu PH, et al. Front Cardiovasc Med. 2022;8(9):794707. eCollection 2022

    Article  Google Scholar 

  31. Ayalasomayajula SP, Langenickel TH, Jordaan P, Zhou W, Chandra P, Albrecht D, Pal P, Rajman I, Sunkara G. Effect of renal function on the pharmacokinetics of LCZ696 (sacubitril/valsartan), an angiotensin receptor neprilysin inhibitor. Eur J Clin Pharmacol. 2016;72:1065–73.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Nephrology and Dialysis, Ospedale Sant’ Antonio Abate, AspTrapani, via Cosenza, Erice (TP), Trapani, Italy

    Leonardo Spatola

  2. Nephrology and Dialysis Unit, “Carlo Urbani” Hospital, Jesi, Italy

    Matthias Zeiler

  3. Division of Nephrology and Dialysis, Ospedale Cannizzaro, Via Messina, Catania, (CT), Italy

    Antonio Granata

Authors
  1. Leonardo Spatola
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Matthias Zeiler
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Antonio Granata
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the review conception, table preparations, and English revision of the manuscript.

Corresponding author

Correspondence to Leonardo Spatola.

Ethics declarations

Ethics Approval

Ethics approval is not requested.

Consent to Participate

No consent to participate was necessary.

Informed Consent

The manuscript is a narrative revision, and no written consent was requested to prepare it.

Consent for Publication

No consent for publication was requested.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Spatola, L., Zeiler, M. & Granata, A. Sacubitril/Valsartan in Dialysis Patients: Update on Current Perspectives. Cardiovasc Drugs Ther (2023). https://doi.org/10.1007/s10557-023-07481-w

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10557-023-07481-w

Keywords

Search

Navigation