Login to MyKarger

New to MyKarger? Click here to sign up.



Login with Facebook

Forgot your password?

Authors, Editors, Reviewers

For Manuscript Submission, Check or Review Login please go to Submission Websites List.

Submission Websites List

Institutional Login
(Shibboleth or Open Athens)

For the academic login, please select your country in the dropdown list. You will be redirected to verify your credentials.

Original Paper

Free Access

Effect of Rosuvastatin on Outcomes in Chronic Haemodialysis Patients: Baseline Data from the AURORA Study

Fellström B.a · Holdaas H.b · Jardine A.G.c · Rose H.d · Schmieder R.e · Wilpshaar W.f · Zannad F.g

Author affiliations

aDepartment of Medical Science, Renal Unit, University Hospital, Uppsala, Sweden; bDepartment of Nephrology, Rikshospitalet, University of Oslo, Oslo, Norway; cBHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow; dAstraZeneca, Macclesfield, UK; eDepartment of Nephrology and Hypertension, Universitätsklinik, Erlangen-Nürnberg, Erlangen, Germany; fformer AstraZeneca, Macclesfield, UK and gClinical Investigation Centre INSERM (CIC), Hôpital Jeanne d’Arc, Toul, France

Corresponding Author

Professor Bengt Fellström

Department of Medical Science, Renal Unit, University Hospital

SE–751 85 Uppsala (Sweden)

Tel. +46 18 611 0000, ext. 4348, Fax +46 18 38304

E-Mail bengt.fellstrom@medsci.uu.se

Related Articles for ""

Kidney Blood Press Res 2007;30:314–322

Do you have an account?

Login Information





Contact Information











I have read the Karger Terms and Conditions and agree.



Abstract

Background: Cardiovascular disease (CVD) is the leading cause of death in patients with end-stage renal disease (ESRD). Aims: AURORA (A study to evaluate the Use of Rosuvastatin in subjects On Regular haemodialysis: an Assessment of survival and cardiovascular events) is the first large-scale international trial to assess the effects of statins on cardiovascular outcomes in patients with ESRD on chronic haemodialysis. Preliminary baseline data from the randomised population are presented. Methods: A total of 2,775 patients from 280 centres in 25 countries were randomised into the study. Patients aged 50–80 years on regular chronic haemodialysis for at least 3 months before screening were eligible for inclusion. They were randomised 1:1 to receive either rosuvastatin 10 mg or placebo daily and assessed throughout the study. Results: The mean age at baseline was 64 years. Most patients were male (62%) and 85% were white. The median time since commencing renal replacement was 32 months. Mean total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels were 4.53 mmol/l (175 mg/dl) and 2.57 mmol/l (99 mg/dl), respectively. Conclusion: Results from the AURORA trial will impact on the current guidelines and use of statins in this patient population.

© 2007 S. Karger AG, Basel


References

  1. Moeller S, Gioberge S, Brown G: ESRD patients in 2001: global overview of patients, treatment modalities and development trends. Nephrol Dial Tranplant2002;17:2071–2076.
  2. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY: Chronic kidney disease and the risks of death, cardiovascular events and hospitalization. N Engl J Med 2004;351:1296–1305.
  3. US Renal Data System: Annual Data Report. Bethesda, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 2005.
  4. Foley RN, Parfrey PS, Sarnak MJ: Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis 1998;32:S112–S119.
  5. Parfrey PS: Cardiac disease in dialysis patients: diagnosis, burden of disease, prognosis, risk factors and management. Nephrol Dial Transplant 2000;15(suppl 5):58–68.
  6. Levey AS, Beto JA, Coronado BE, Eknoyan G, Foley RN, Kasiske BL, Klag MJ, Mailloux LU, Manske CL, Meyer KB, Parfrey PS, Pfeffer MA, Wenger NK, Wilson PW, Wright JT Jr: Controlling the epidemic of cardiovascular disease in chronic renal disease: What do we know? What do we need to learn? Where do we go from here? National Kidney Foundation Task Force on Cardiovascular Disease. Am J Kidney Dis1998;32:853–906.
  7. Mackay J, Mensah GA: The Atlas of Heart Disease and Stroke. Geneva, World Health Organization, 2004.
  8. 4 S (Scandinavian Simvastatin Survival Study Group): Randomised trial of cholesterol lowering in 4,444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994;344:1383–1389.
  9. Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, McKillop JH, Packard CJ; West of Scotland Coronary Prevention Study Group: Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 1995;333:1301–1307.
  10. Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG, Brown L, Warnica JW, Arnold JM, Wun CC, Davis BR, Braunwald E: The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial Investigators. N Engl J Med 1996;335:1001–1009.
  11. Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA, Langendorfer A, Stein EA, Kruyer W, Gotto AM Jr: Primary prevention of acute coronary events with lova-statin in men and women with average cholesterol levels. Results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA 1998;279:1615–1622.
  12. The Long-term Intervention with Prava-statin in Ischemic Disease (LIPID) Study Group: Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med 1998;339:1349–1357.
  13. Heart Protection Study Collaborative Group: MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360:7–22.
  14. Shepherd J, Blauw GJ, Murphy MB, Bollen EL, Buckley BM, Cobbe SM, Ford I, Gaw A, Hyland M, Jukema JW, Kamper AM, Macfarlane PW, Meinders AE, Norrie J, Packard CJ, Perry IJ, Stott DJ, Sweeney BJ, Twomey C, Westendorp RG; PROSPER study group: PROspective Study of Pravastatin in the Elderly at Risk. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002;360:1623–1630.
  15. Sever PS, Dahlöf B, Poulter NR, Wedel H, Beevers G, Caulfield M, Collins R, Kjeldsen SE, Kristinsson A, McInnes GT, Mehlsen J, Nieminen M, O’Brien E, Östergren J; ASCOT investigators: Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet 2003;361:1149–1158.
  16. Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil H, Livingstone S, Thomason MJ, Mackness MI, Charlton-Menys V, Fuller JH; CARDS investigators: Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet2004;364:685–696.
  17. Shoji T, Nishizawa Y, Kawagishi T, Tanaka M, Kawasaki K, Tabata T, Inoue T, Morii H: Atherogenic lipoprotein changes in the absence of hyperlipidemia in patients with chronic renal failure treated by hemodialysis. Atherosclerosis 1997;131:229–236.
  18. Shoji T, Nishizawa Y, Kawagishi T, Kawasaki K, Taniwaki H, Tabata T, Inoue T, Morii H: Intermediate-density lipoprotein as an independent risk factor for aortic atherosclerosis in hemodialysis patients. J Am Soc Nephrol 1998;9:1277–1284.
  19. Deighan CJ, Caslake MJ, McConnell M, Boulton-Jones JM, Packard CJ: Atherogenic lipoprotein phenotype in end-stage renal failure: origin and extent of small dense low-density lipoprotein formation. Am J Kidney Dis 2000;35:852–862.
  20. Stenvinkel P, Heimburger O, Paultre F, Diczfalusy U, Wang T, Berglund L, Jogestrand T: Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure. Kidney Int 1999:55:1899–1911.
  21. Annuk M, Zilmer M, Lind L, Linde T, Fellstrom B: Oxidative stress and endothelial function in chronic renal failure. J Am Soc Nephrol 2001;12:2747–2752.
  22. Annuk M, Lind L, Linde T, Fellström B: Impaired endothelium-dependent vasodilation in renal failure in humans. Nephrol Dial Transplant 2001;16:302–306.
  23. Locatelli F, Canaud B, Eckardt KU, Stenvinkel P, Wanner C, Zoccali C: Oxidative stress in end-stage renal disease: an emerging threat to patient outcome. Nephrol Dial Transplant 2003;18:1272–1280.
  24. Laufs U: Beyond lipid-lowering: effects of statins on endothelial nitric oxide. Eur J Clin Pharmacol 2003;58:719–731.
  25. Rosenson RS: Statins in atherosclerosis: lipid-lowering agents with antioxidant capabilities. Atherosclerosis2004;173:1–12.
  26. Field KM: Effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on high-sensitivity C-reactive protein levels. Pharmacotherapy 2005;25:1365–1377.
  27. Seliger SL, Weiss NS, Gillen DL, Kestenbaum B, Ball A, Sherrard DJ, Stehman-Breen CO: HMG-CoA reductase inhibitors are associated with reduced mortality in ESRD patients. Kidney Int 2002;61:297–304.
  28. National Kidney Foundation: K/DOQI clinical practice guidelines for managing dyslipidemias in chronic kidney disease. Am J Kidney Dis 2003;41(suppl 3):S1–S92.
  29. Wanner C, Krane V, März W, Olschewski M, Mann JF, Ruf G, Ritz E; for the German Diabetes and Dialysis Study Investigators: Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med2005;353:238–242.
  30. Blasetto JW, Stein EA, Brown WV, Chitra R, Raza A: Efficacy of rosuvastatin compared with other statins at selected starting doses in hypercholesterolemic patients and in special population groups. Am J Cardiol 2003;91:3C–10C.
  31. Chapman MJ, Caslake M, Packard C, McTaggart F: New dimension of statin action on ApoB atherogenicity. Clin Cardiol 2003;26(1 suppl 1):I7–I10.
    External Resources
  32. Fellström B, Zannad F, Schmieder R, Holdaas H, Jardine A, Rose H, Wilpshaar W; AURORA Study Group: Effect of rosuvastatin on outcomes in chronic haemodialysis patients: design and rationale of the AURORA study. Curr Control Trials CardiovascMed2005;6:9.
  33. Holdaas H, Fellström B, Jardine AG, Holme I, Nyberg G, Fauchald P, Gronhagen-Riska C, Madsen S, Neumayer HH, Cole E, Maes B, Ambuhl P, Olsson AG, Hartmann A, Solbu DO, Pedersen TR; Assessment of LEscol in Renal Transplantation (ALERT) Study Investigators: Effect of fluvastatin on cardiac outcomes in renal transplant recipients: a multicentre, randomised, placebo-controlled trial. Lancet 2003;361:2024–2031.
  34. Jindal KK, Manuel A, Goldstein MB: Percent reduction in blood urea concentration during hemodialysis (PRU): a simple and accurate method to estimate Kt/V urea. ASAIO Trans 1987;33:286–288.
  35. National Kidney Foundation: K/DOQI clinical practice guidelines for anemia of chronic kidney disease, 2000. Am J Kidney Dis 2001;27(suppl 1):S182–S238.
  36. Locatelli F, Aljama P, Barany P, Canaud B, Carrera F, Eckardt KU, Horl WH, Macdougal IC, Macleod A, Wiecek A, Cameron S; European Best Practice Guidelines Working Group: Revised European best practice guidelines for the management of anaemia in patients with chronic renal failure. Nephrol Dial Transplant 2004;19(suppl 2):ii1–ii47.
    External Resources
  37. Kronenberg F, Konig P, Neyer U, Auinger M, Pribasnig A, Lang U, Reitinger J, Pinter G, Utermann G, Dieplinger H: Multicenter study of lipoprotein(a) and apolipoprotein(a) phenotypes in patients with end-stage renal disease treated by hemodialysis or continuous ambulatory peritoneal dialysis. J Am Soc Nephrol 1995;6:110–120.
  38. Kushiya F, Wada H, Sakakura M, Mori Y, Gabazza EC, Nishikawa M, Nobori T, Noguchi M, Izumi K, Nakasaki T, Takagi M, Shiku H: Effects of lipid abnormalities on arteriosclerosis and hemostatic markers in patients under hemodialysis. Clin Appl Thromb Hemost 2003;9:203–210.
  39. Wanner C, Krane V, Marz W, Olschewski M, Asmus HG, Kramer W, Kuhn KW, Kutemeyer H, Mann JF, Ruf G, Ritz E; Deutsche Diabetes-Dialyse-Studie (4D) Study Group: Randomized controlled trial on the efficacy and safety of atorvastatin in patients with type 2 diabetes on hemodialysis (4D study): demographic and baseline characteristics. Kidney Blood Press Res 2004;27:259–266.
  40. Meisinger C Baumert J, Khuseyinova N, Loewel H, Koenig W: Plasma oxidized low-density lipoprotein, a strong predictor for acute coronary heart disease events in apparently healthy, middle-aged men from the general population. Circulation 2005;112:651–657.
  41. Diepeveen SH, Verhoeven GW, Van Der Palen J, Dikkeschei LD, Van Tits LJ, Kolsters G, Offerman JJ, Bilo HJ, Stalenhoef AF: Effects of atorvastatin and vitamin E on lipoproteins and oxidative stress in dialysis patients: a randomised-controlled trial. J Intern Med 2005;257:438–445.
  42. Baigent C, Landry M: Study of Heart and Renal Protection (SHARP). Kidney Int 2003;63(suppl 84):207–210.
    External Resources
  43. Holdaas H, Fellström B, Cole E, Nyberg G, Olsson AG, Pedersen TR, Madsen S, Gronhagen-Riska C, Neumayer HH, Maes B, Ambuhl P, Hartmann A, Staffler B, Jardine AG; Assessment of LEscol in Renal Transplantation (ALERT) Study Investigators: Long term cardiac outcomes in renal transplant recipients receiving fluvastatin: the ALERT extension study. Am J Transplant 2005;5:2929–2936.
  44. Clearfield MB, Amerena J, Bassand JP, Garcia HR, Miller SS, Sosef FF, Palmer MK, Bryzinski BS: Comparison of the efficacy and safety of rosuvastatin 10 mg and atorvastatin 20 mg in high-risk patients with hypercholesterolemia: Prospective study to evaluate the Use of Low doses of the Statins Atorvastatin and Rosuvastatin (PULSAR). Trials 2006;7:35.
    External Resources
  45. Amarenco P, Bogousslavsky J, Callahan A 3rd, Goldstein LB, Hennerici M, Rudolph AE, Sillesen H, Simunovic L, Szarek M, Welch KM, Zivin JA; Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators: High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 2006;355:549–559.
  46. Ballantyne CM, Bertolami M, Hernandez Garcia HR, Nul D, Stein EA, Theroux P, Weiss R, Cain VA, Raichlen JS: Achieving LDL cholesterol, non-HDL cholesterol, and apolipoprotein B target levels in high-risk patients: Measuring Effective Reductions in Cholesterol Using Rosuvastatin TherapY (MERCURY) II. Am Heart J 2006;151:975.e1–e9.
  47. Jones PH, Davidson MH, Stein EA, Bays HE, McKenney JM, Miller E, Cain VA, Blasetto JW; STELLAR Study Group: Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR Trial). Am J Cardiol2003;92:152–160.
  48. Schuster H, Barter PJ, Stender S, Cheung RC, Bonnet J, Morrell JM, Watkins C, Kallend D, Raza A; Effective Reductions in Cholesterol Using Rosuvastatin Therapy I Study Group: Effects of switching statins on achievement of lipid goals: Measuring Effective Reductions in Cholesterol using Rosuvastatin therapY (MERCURY I) study. Am Heart J 2004;147:705–712.

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: April 26, 2007
Accepted: May 11, 2007
Published online: July 31, 2007
Issue release date: September 2007

Number of Print Pages: 9
Number of Figures: 2
Number of Tables: 5

ISSN: 1420-4096 (Print)
eISSN: 1423-0143 (Online)

For additional information: https://www.karger.com/KBR


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.