Skip to main content

Advertisement

SpringerLink
Log in

Effects of cilostazol and renin-angiotensin system (RAS) blockers on the renal disease progression of Korean patients: a retrospective cohort study

  • Research Article
  • Published:
International Journal of Clinical Pharmacy Aims and scope Submit manuscript

Abstract

Background Decline in estimated glomerular filtration rate (eGFR) is an important surrogate marker for the assessment of renal function. Addition of a second agent to angiotensin-converting-enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) treatment may improve current therapeutic strategies aimed at suppressing renal disease progression. Objective To determine the effect of cilostazol in combination with ACEI or ARB treatment on the decline in eGFR. Setting A tertiary hospital in Korea. Method In an observational cohort study, we analyzed 5505 patients who were prescribed ACEI or ARB and cilostazol or other antiplatelet agents. Main outcome measure The primary outcome assessed was worsening of renal function defined as a 30% decline in eGFR per year. The secondary outcomes included commencement of dialysis, renal transplantation, death, myocardial infarction, and ischemic stroke. Results Following propensity score matching, eGFR decreased over time in the majority of patients, but the decline was less in patients in the cilostazol treated (CT) group of stage 1–2 category compared to the cilostazol untreated (CU) group (OR 0.80; 95% CI 0.66–0.98). In the subgroup analysis, the strongest effect in slowing eGFR decline was observed in CT patients at a high risk of diabetes (OR 0.782; 95% CI 0.615–0.993) and the elderly (OR 0.693; 95% CI 0.504–0.953) in the stage 1–2 category. No significant increase in cardiovascular risk was observed between the CT and CU groups. Conclusion Treatment with cilostazol plus ACEI or ARB was observed to prevent worsening of renal progression in patients in the stages 1–2.

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
Fig. 2

Similar content being viewed by others

References

  1. Park JI, Baek H, Jung HH. Prevalence of chronic kidney disease in Korea: the Korean National Health and Nutritional Examination Survey 2011–2013. J Korean Med Sci. 2016;31(6):915–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Hazzan AD, Halinski C, Agoritsas S, Fishbane S, DeVita MV. Epidemiology and challenges to the management of advanced CKD. Adv Chronic Kidney Dis. 2016;23(4):217–21.

    Article  PubMed  Google Scholar 

  3. Webster AC, Nagler EV, Morton RL, Masson P. Chronic kidney disease. Lancet. 2016;389(10075):1238–52.

    Article  PubMed  Google Scholar 

  4. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. NEJM. 2004;351(13):1296–305.

    Article  CAS  PubMed  Google Scholar 

  5. Remuzzi G, Perico N, Macia M, Ruggenenti P. The role of renin-angiotensin-aldosterone system in the progression of chronic kidney disease. Kidney Int Suppl. 2005;99:S57–65.

    Article  CAS  Google Scholar 

  6. Stefoni S, Cianciolo G, Baraldi O, Iorio M, Angelini ML. Emerging drugs for chronic kidney disease. Expert Opin Emerg Drugs. 2014;19(2):183–99.

    Article  CAS  PubMed  Google Scholar 

  7. Molnar MZ, Kalantar-Zadeh K, Lott EH, Lu JL, Malakauskas SM, Ma JZ, et al. Angiotensin-converting enzyme inhibitor, angiotensin receptor blocker use, and mortality in patients with chronic kidney disease. J Am Coll Cardiol. 2014;63(7):650–8.

    Article  CAS  PubMed  Google Scholar 

  8. MacKinnon M, Shurraw S, Akbari A, Knoll GA, Jaffey J, Clark HD, et al. Combination therapy with an angiotensin receptor blocker and an ACE inhibitor in proteinuric renal disease: a systematic review of the efficacy and safety data. Am J Kidney Dis. 2006;48(1):8–20.

    Article  CAS  PubMed  Google Scholar 

  9. Egido J, Fernandez-Fernandez B, Ortiz A, Mas S, Gómez-Guerrero C. Standard and novel therapeutic approaches to diabetic nephropathy. Port J Nephrol Hypertens. 2015;29(2):101–7.

    Google Scholar 

  10. Fried LF, Emanuele N, Zhang JH, Brophy M, Conner TA, Duckworth W, et al. Combined angiotensin inhibition for the treatment of diabetic nephropathy. NEJM. 2013;369(20):1892–903.

    Article  CAS  PubMed  Google Scholar 

  11. Zou Y, Hu C, Ye W, Fan L, Xu L, Zhang A, et al. Long-term clinical efficacy and safety of adding cilostazol to dual antiplatelet therapy after drug-eluting stent implantation in coronary arteries: a meta-analysis of randomized controlled trials. Thromb Res. 2015;136(5):870–7.

    Article  CAS  PubMed  Google Scholar 

  12. Ragab D, Abdallah DM, El-Abhar HS. Cilostazol renoprotective effect: modulation of PPAR-gamma, NGAL, KIM-1 and IL-18 underlies its novel effect in a model of ischemia-reperfusion. PLoS ONE. 2014;9(5):e95313.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Wang X, Yan L, Chen W, Xu L, Zhang X. The renal protective effects of cilostazol on suppressing pathogenic thrombospondin-1 and transforming growth factor-beta expression in streptozotocin-induced diabetic rats. J Int Med Res. 2009;37(1):145–53.

    Article  PubMed  Google Scholar 

  14. Tang WH, Lin FH, Lee CH, Kuo FC, Hsieh CH, Hsiao FC, et al. Cilostazol effectively attenuates deterioration of albuminuria in patients with type 2 diabetes: a randomized, placebo-controlled trial. Endocrine. 2014;45(2):293–301.

    Article  CAS  PubMed  Google Scholar 

  15. International K. Is a decline in estimated GFR an appropriate surrogate end point for renoprotection drug trials? Int Soc Nephrol. 2014;85:723–7.

    Google Scholar 

  16. Beddhu S, Samore MH, Roberts MS, Stoddard GJ, Pappas LM, Cheung AK, et al. Creatinine production, nutrition, and glomerular filtration rate estimation. J Am Soc Nephrol. 2003;14(4):1000–5.

    Article  PubMed  Google Scholar 

  17. Cartet-Farnier E, Goutelle-Audibert L, Maire P, De la Gastine B, Goutelle S. Implications of using the MDRD or CKD-EPI equation instead of the Cockcroft-Gault equation for estimating renal function and drug dosage adjustment in elderly patients. Fundam Clin Pharmacol. 2017;31(1):110–9.

    Article  CAS  PubMed  Google Scholar 

  18. International K. Is a decline in estimated GFR an appropriate surrogate end point for renoprotection drug trials? Int Soc Nephrol. 2014;85:723–7.

    Google Scholar 

  19. Jha V, Garcia-Garcia G, Iseki K, Li Z, Naicker S, Plattner B, et al. Chronic kidney disease: global dimension and perspectives. Lancet. 2013;382(9888):260–72.

    Article  PubMed  Google Scholar 

  20. KDIGO. clinical practice guideline for the evaluation and management of chronic kidney diseas. Kidney Int Suppl. 2012;2013(3):136–50.

    Google Scholar 

  21. Mann JF, Schmieder RE, McQueen M, Dyal L, Schumacher H, Pogue J, et al. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet. 2008;372(9638):547–53.

    Article  CAS  PubMed  Google Scholar 

  22. Makani H, Bangalore S, Desouza KA, Shah A, Messerli FH. Efficacy and safety of dual blockade of the renin-angiotensin system: meta-analysis of randomised trials. BMJ. 2013;346:f360.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Jiao XM, Jiao XJ, Zhang XG, Xu XP, Wu JX, Yao L, et al. Cilostazol reduces microalbuminuria in type 2 diabetic nephropathy. Chin Med J. 2013;126(22):4395–6.

    PubMed  Google Scholar 

  24. Wannamethee SG, Shaper AG, Perry IJ. Serum creatinine concentration and risk of cardiovascular disease: a possible marker for increased risk of stroke. Stroke J Cereb Circ. 1997;28(3):557–63.

    Article  CAS  Google Scholar 

  25. Khan SS, Kazmi WH, Abichandani R, Tighiouart H, Pereira BJ, Kausz AT, et al. Health care utilization among patients with chronic kidney disease. Kidney Int. 2002;62(1):229–36.

    Article  PubMed  Google Scholar 

  26. Earlier endpoints proposed for chronic kidney disease trials. Nephrol News. 2012. https://www.kidney.org/news/newsroom/nr/Earlier-Endpoints-Proposed-for-Clinical-Trials-in-CKD. Accessed 30 July 2017.

  27. Schnaper HW, Furth SL, Yao LP. Defining new surrogate markers for CKD progression. Pediatr Nephrol. 2015;30(2):193–8.

    Article  PubMed  Google Scholar 

  28. Wang F, Li M, Cheng L, Zhang T, Hu J, Cao M, et al. Intervention with cilostazol attenuates renal inflammation in streptozotocin-induced diabetic rats. Life Sci. 2008;83(25–26):828–35.

    Article  CAS  PubMed  Google Scholar 

  29. Agrawal NK, Maiti R, Dash D, Pandey BL. Cilostazol reduces inflammatory burden and oxidative stress in hypertensive type 2 diabetes mellitus patients. Pharmacol Res. 2007;56(2):118–23.

    Article  CAS  PubMed  Google Scholar 

  30. Goto S. Cilostazol: potential mechanism of action for antithrombotic effects accompanied by a low rate of bleeding. Atheroscler Suppl. 2005;6(4):3–11.

    Article  CAS  PubMed  Google Scholar 

  31. Suzuki K, Uchida K, Nakanishi N, Hattori Y. Cilostazol activates AMP-activated protein kinase and restores endothelial function in diabetes. Am J Hypertens. 2008;21(4):451–7.

    Article  CAS  PubMed  Google Scholar 

  32. Service NHI. Koean diabetes fact sheet. Seoul: Korean Diabetes Association; 2015.

    Google Scholar 

  33. Palmer SC, Di Micco L, Razavian M, Craig JC, Perkovic V, Pellegrini F, et al. Antiplatelet agents for chronic kidney disease. Cochrane Database Syst Rev. 2013;2:CD008834.

    Google Scholar 

  34. Saran RDD, Wolfe RA, Gillespie B, Held PJ, Young EW. Association between vascular access failure and the use of specific drugs: the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis. 2002;40(6):1255–63.

    Article  CAS  PubMed  Google Scholar 

  35. Ghorbani A, Aalamshah M, Shahbazian H, Ehsanpour A, Aref A. Randomized controlled trial of clopidogrel to prevent primary arteriovenous fistula failure in hemodialysis patients. Indian J Nephrol. 2009;19(2):57–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Chang CC, Liou HH, Wu CL, Chang CB, Chang YJ, Chiu PF, et al. Warfarin slows deterioration of renal function in elderly patients with chronic kidney disease and atrial fibrillation. Clin Interv Aging. 2013;8:523–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation funded by the Ministry of Science, ICT & Future Planning, Republic of Korea (No. 2013M3A9B5075838).

Funding

None

Conflicts of interest

The authors declare that they have no conflicts of interest.

Author information

Authors and Affiliations

  1. Division of Clinical Pharmacy, College of Pharmacy, Ajou University, 206 Worldcup-ro, Yeongtong-gu, Suwon, 16499, South Korea

    Yoojin Noh, Jimin Lee, Sooyoung Shin & Sukhyang Lee

  2. Department of Nephrology, College of Medicine, Ajou University, Suwon, South Korea

    Inwhee Park

  3. College of Pharmacy, The Catholic University of Korea, Bucheon, South Korea

    Soo Kyung Bae & Euichul Oh

Authors
  1. Yoojin Noh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jimin Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sooyoung Shin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Inwhee Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Soo Kyung Bae
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Euichul Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sukhyang Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sukhyang Lee.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Noh, Y., Lee, J., Shin, S. et al. Effects of cilostazol and renin-angiotensin system (RAS) blockers on the renal disease progression of Korean patients: a retrospective cohort study. Int J Clin Pharm 40, 160–168 (2018). https://doi.org/10.1007/s11096-017-0578-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11096-017-0578-4

Keywords

Search

Navigation