Skip to main content

Advertisement

SpringerLink
Log in

Comparative effectiveness of angiotensin receptor blockers vs. angiotensin-converting enzyme inhibitors on cardiovascular outcomes in patients initiating peritoneal dialysis

  • Original Article
  • Published:
Journal of Nephrology Aims and scope Submit manuscript

Abstract

Background

There is evidence that angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-II receptor blockers (ARB) may reduce cardiovascular (CV) risk in patients undergoing peritoneal dialysis (PD), but no studies have compared the effectiveness between these drug classes. In this observational cohort study, we compared the association of ARB vs. ACEI use on CV outcomes in patients initiating PD.

Methods

We identified from the US Renal Data System all adult patients who initiated PD from 2007 to 2011 and participated in Medicare Part D, a federal prescription drug benefits program, for the first 90 days of dialysis. Patients who filled a prescription for an ACEI or ARB in those 90 days were considered users. We excluded patients who used both ACEI and ARB. We applied Cox proportional hazards regression to an inverse probability of treatment-weighted cohort to estimate the hazard ratios (HR) for the combined outcome of all-cause death, ischemic stroke, or myocardial infarction; all-cause mortality; and CV death.

Results

Among 1892 patients using either drug class, 39 % were ARB users. We observed 624 events over 2,898 person-years of follow-up, for a composite event rate of 22 events per 100 person-years. We observed no differences between ARB vs. ACEI users: composite outcome HR 0.94, 95 % confidence interval (CI) 0.79–1.11; all-cause mortality HR 0.92, 95 % CI 0.76–1.10; CV death HR: 1.06, 95 % CI 0.80–1.41.

Conclusion

We identified no significant difference in the risks of CV events or death between users of ARBs vs. ACEIs in patients initiating PD, thus supporting their mostly interchangeable use in this population.

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

References

  1. USRDS 2014 Annual Data Report: Atlas of End-Stage Renal Disease in the United States (2014) U.S. Renal Data System. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD

  2. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Masoudi FA, McBride PE, McMurray JJ, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WH, Tsai EJ, Wilkoff BL (2013) 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 128(16):1810–1852. doi:10.1161/CIR.0b013e31829e8807

    Article  PubMed  Google Scholar 

  3. American Diabetes A (2016) 8. Cardiovascular Disease and Risk Management. Diabetes Care 39(Suppl 1):S60–S71. doi:10.2337/dc16-S011

  4. James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, Lackland DT, LeFevre ML, MacKenzie TD, Ogedegbe O, Smith SC Jr, Svetkey LP, Taler SJ, Townsend RR, Wright JT Jr, Narva AS, Ortiz E (2014) 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 311(5):507–520. doi:10.1001/jama.2013.284427

    Article  CAS  PubMed  Google Scholar 

  5. Fang W, Oreopoulos DG, Bargman JM (2008) Use of ACE inhibitors or angiotensin receptor blockers and survival in patients on peritoneal dialysis. Nephrol Dial Transplant 23(11):3704–3710

    Article  CAS  PubMed  Google Scholar 

  6. Berger AK, Duval S, Krumholz HM (2003) Aspirin, beta-blocker, and angiotensin-converting enzyme inhibitor therapy in patients with end-stage renal disease and an acute myocardial infarction. J Am Coll Cardiol 42(2):201–208

    Article  CAS  PubMed  Google Scholar 

  7. Suzuki H, Kanno Y, Sugahara S, Ikeda N, Shoda J, Takenaka T, Inoue T, Araki R (2008) Effect of angiotensin receptor blockers on cardiovascular events in patients undergoing hemodialysis: an open-label randomized controlled trial. Am J Kidney Dis 52(3):501–506. doi:10.1053/j.ajkd.2008.04.031

    Article  CAS  PubMed  Google Scholar 

  8. Takahashi A, Takase H, Toriyama T, Sugiura T, Kurita Y, Ueda R, Dohi Y (2006) Candesartan, an angiotensin II type-1 receptor blocker, reduces cardiovascular events in patients on chronic haemodialysis–a randomized study. Nephrol Dial Transplant 21(9):2507–2512. doi:10.1093/ndt/gfl293

    Article  CAS  PubMed  Google Scholar 

  9. Shen JI, Saxena AB, Montez-Rath ME, Chang TI, Winkelmayer WC (2016) Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use and cardiovascular outcomes in patients initiating peritoneal dialysis. Nephrol Dial Transplant. doi:10.1093/ndt/gfw053

    Google Scholar 

  10. Kidney Disease Outcomes Quality I (2004) K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis 43(5 Suppl 1):S1–S290

    Google Scholar 

  11. Peritoneal Dialysis Adequacy Work G (2006) Clinical practice guidelines for peritoneal dialysis adequacy. Am J Kidney Dis 48(Suppl 1):S98–S129. doi:10.1053/j.ajkd.2006.04.006

    Google Scholar 

  12. Chan KE, Ikizler TA, Gamboa JL, Yu C, Hakim RM, Brown NJ (2011) Combined angiotensin-converting enzyme inhibition and receptor blockade associate with increased risk of cardiovascular death in hemodialysis patients. Kidney Int 80(9):978–985. doi:10.1038/ki.2011.228

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Kiyota Y, Schneeweiss S, Glynn RJ, Cannuscio CC, Avorn J, Solomon DH (2004) Accuracy of Medicare claims-based diagnosis of acute myocardial infarction: estimating positive predictive value on the basis of review of hospital records. Am Heart J 148(1):99–104. doi:10.1016/j.ahj.2004.02.013

    Article  PubMed  Google Scholar 

  14. Kumamaru H, Judd SE, Curtis JR, Ramachandran R, Hardy NC, Rhodes JD, Safford MM, Kissela BM, Howard G, Jalbert JJ, Brott TG, Setoguchi S (2014) Validity of claims-based stroke algorithms in contemporary Medicare data: reasons for geographic and racial differences in stroke (REGARDS) study linked with medicare claims. Circ Cardiovasc Qual Outcomes 7(4):611–619. doi:10.1161/CIRCOUTCOMES.113.000743

    Article  PubMed  PubMed Central  Google Scholar 

  15. WWAMI Ruca Rural Health Research Center. http://depts.washington.edu/uwruca/ruca-data.php. Accessed January 5, 2012 2012

  16. U.S. Census Bureau GD Census Bureau Regions and Divisions with State FIPS Codes. http://www.census.gov/geo/www/reg_div.txt. Accessed January 5, 2012 2012

  17. Shen JI, Mitani AA, Chang TI, Winkelmayer WC (2013) Use and safety of heparin-free maintenance hemodialysis in the USA. Nephrol Dial Transplant 28(6):1589–1602. doi:10.1093/ndt/gft067

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Chang TI, Shilane D, Kazi DS, Montez-Rath ME, Hlatky MA, Winkelmayer WC (2012) Multivessel coronary artery bypass grafting versus percutaneous coronary intervention in ESRD. J Am Soc Nephrol 23(12):2042–2049. doi:10.1681/ASN.2012060554

    Article  PubMed  PubMed Central  Google Scholar 

  19. Austin PC (2009) Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples. Stat Med 28(25):3083–3107. doi:10.1002/sim.3697

    Article  PubMed  PubMed Central  Google Scholar 

  20. Robins JM, Hernan MA, Brumback B (2000) Marginal structural models and causal inference in epidemiology. Epidemiology 11(5):550–560

    Article  CAS  PubMed  Google Scholar 

  21. Shen JI, Saxena AB, Montez-Rath ME, Winkelmayer WC (2016) Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use and cardiovascular outcomes in patients initiating peritoneal dialysis. Nephrol Dial Transplant. doi:10.1093/ndt/gfw053

    Google Scholar 

  22. Witherow FN, Helmy A, Webb DJ, Fox KA, Newby DE (2001) Bradykinin contributes to the vasodilator effects of chronic angiotensin-converting enzyme inhibition in patients with heart failure. Circulation 104(18):2177–2181

    Article  CAS  PubMed  Google Scholar 

  23. Hornig B, Arakawa N, Haussmann D, Drexler H (1998) Differential effects of quinaprilat and enalaprilat on endothelial function of conduit arteries in patients with chronic heart failure. Circulation 98(25):2842–2848

    Article  CAS  PubMed  Google Scholar 

  24. Miyazaki H, Matsuoka H, Itabe H, Usui M, Ueda S, Okuda S, Imaizumi T (2000) Hemodialysis impairs endothelial function via oxidative stress: effects of vitamin E-coated dialyzer. Circulation 101(9):1002–1006

    Article  CAS  PubMed  Google Scholar 

  25. van Guldener C, Janssen MJ, Lambert J, Steyn M, Donker AJ, Stehouwer CD (1998) Endothelium-dependent vasodilatation is impaired in peritoneal dialysis patients. Nephrol Dial Transplant 13(7):1782–1786

    Article  PubMed  Google Scholar 

  26. Baker WL, Coleman CI, Kluger J, Reinhart KM, Talati R, Quercia R, Phung OJ, White CM (2009) Systematic review: comparative effectiveness of angiotensin-converting enzyme inhibitors or angiotensin II-receptor blockers for ischemic heart disease. Ann Intern Med 151(12):861–871. doi:10.7326/0003-4819-151-12-200912150-00162

    Article  PubMed  Google Scholar 

  27. van Vark LC, Bertrand M, Akkerhuis KM, Brugts JJ, Fox K, Mourad JJ, Boersma E (2012) Angiotensin-converting enzyme inhibitors reduce mortality in hypertension: a meta-analysis of randomized clinical trials of renin-angiotensin-aldosterone system inhibitors involving 158,998 patients. Eur Heart J 33(16):2088–2097. doi:10.1093/eurheartj/ehs075

    Article  PubMed  PubMed Central  Google Scholar 

  28. Li EC, Heran BS, Wright JM (2014) Angiotensin converting enzyme (ACE) inhibitors versus angiotensin receptor blockers for primary hypertension. Cochrane Database Syst Rev 8:CD009096. doi:10.1002/14651858.CD009096.pub2

  29. Xie X, Liu Y, Perkovic V, Li X, Ninomiya T, Hou W, Zhao N, Liu L, Lv J, Zhang H, Wang H (2015) Renin-Angiotensin System Inhibitors and Kidney and Cardiovascular Outcomes in Patients With CKD: A Bayesian Network Meta-analysis of Randomized Clinical Trials. Am J Kidney Dis. doi:10.1053/j.ajkd.2015.10.011

    PubMed Central  Google Scholar 

  30. Cheng J, Zhang W, Zhang X, Han F, Li X, He X, Li Q, Chen J (2014) Effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on all-cause mortality, cardiovascular deaths, and cardiovascular events in patients with diabetes mellitus: a meta-analysis. JAMA Intern Med 174(5):773–785. doi:10.1001/jamainternmed.2014.348

    Article  CAS  PubMed  Google Scholar 

  31. Wu HY, Huang JW, Lin HJ, Liao WC, Peng YS, Hung KY, Wu KD, Tu YK, Chien KL (2013) Comparative effectiveness of renin-angiotensin system blockers and other antihypertensive drugs in patients with diabetes: systematic review and bayesian network meta-analysis. BMJ 347:f6008. doi:10.1136/bmj.f6008

    Article  PubMed  PubMed Central  Google Scholar 

  32. Tomiyama H, Kushiro T, Abeta H, Ishii T, Takahashi A, Furukawa L, Asagami T, Hino T, Saito F, Otsuka Y et al (1994) Kinins contribute to the improvement of insulin sensitivity during treatment with angiotensin converting enzyme inhibitor. Hypertension 23(4):450–455

    Article  CAS  PubMed  Google Scholar 

  33. Krediet RT, Balafa O (2010) Cardiovascular risk in the peritoneal dialysis patient. Nat Rev Nephrol 6(8):451–460. doi:10.1038/nrneph.2010.68

    Article  PubMed  Google Scholar 

  34. Erickson KF, Tan KB, Winkelmayer WC, Chertow GM, Bhattacharya J (2013) Variation in nephrologist visits to patients on hemodialysis across dialysis facilities and geographic locations. Clin J Am Soc Nephrol 8(6):987–994. doi:10.2215/CJN.10171012

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This work was supported by Grants F32DK096765 (JIS), K23DK103972 (JIS), and K23DK095914 (TIC) from the National Institute of Diabetes, Digestive, and Kidney Diseases (NIDDK, Bethesda, MA, USA). The Stanford Nephrology fellowship program was supported by Grant T32DK007357. JIS was also supported by the Satellite Dialysis Clinical Investigator Award from the National Kidney Foundation, Grant KL2TR000122 from the NIH/National Center for Advancing Translational Science (NCATS), and a generous gift honoring the life and work of nephrologist Henry Shavelle, MD. The data reported here have been supplied by the United States Renal Data System (USRDS). The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as official policy or interpretation of the US government.

Author information

Authors and Affiliations

  1. Division of Nephrology and Hypertension, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1000 W. Carson St., Box 406, Torrance, CA, 90509, USA

    Jenny I. Shen & Lynn Leng

  2. Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Palo Alto, CA, USA

    Jenny I. Shen, Anjali B. Saxena, Maria E. Montez-Rath, Tara I. Chang & Wolfgang C. Winkelmayer

  3. Selzman Institute for Kidney Health, Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA

    Wolfgang C. Winkelmayer

Authors
  1. Jenny I. Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anjali B. Saxena
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maria E. Montez-Rath
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lynn Leng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tara I. Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wolfgang C. Winkelmayer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jenny I. Shen.

Ethics declarations

Research involving human participants

Institutional Review Boards of Stanford University and Baylor College of Medicine approved the study. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

For this type of study formal consent is not required.

Conflict of interest

ABS is on the speaker’s bureau for Baxter International. None of the other authors have financial conflicts of interest to disclose.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shen, J.I., Saxena, A.B., Montez-Rath, M.E. et al. Comparative effectiveness of angiotensin receptor blockers vs. angiotensin-converting enzyme inhibitors on cardiovascular outcomes in patients initiating peritoneal dialysis. J Nephrol 30, 281–288 (2017). https://doi.org/10.1007/s40620-016-0340-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40620-016-0340-3

Keywords

Search

Navigation