Skip to main content
SpringerLink
Log in

Atorvastatin effect on systemic lupus erythematosus disease activity: a double-blind randomized clinical trial

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

We aimed to evaluate the therapeutic effects of atorvastatin on systemic lupus erythematosus disease activity index (SLEDAI). Ninety patients with SLE were consented and randomized to receive either atorvastatin, 20 mg/day, or placebo for 3 months. The primary outcome was change in SLEDAI. Lipids, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were assessed as secondary end points. Analysis was done by “intention to treat” (ITT) as the primary analysis and “treatment completed analysis” (TCA) as the supplementary analysis. Demographic features, baseline characteristics, and distribution of medications were not significantly different between the two groups. Mean SLEDAI score at baseline in both groups was 3 ± 0.5. By TCA and ITT, mean SLEDAI scores decreased to 1.7 ± 0.4 and 2.7 ± 0.5, respectively, in the atorvastatin group and 3 ± 0.4 and 3 ± 0.5, respectively, in the control group. The difference between the two groups after intervention was significant by TCA (P < 0.05) and nonsignificant by ITT analysis (P = 0.1). The effect of atorvastatin therapy on lupus activity was inconclusive.

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. Avina-Zubieta JA, Choi HK, Sadatsafavi M, Etminan M, Esdaile JM, Lacaille D (2008) Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Rheum 59(12):1690–1697

    Article  PubMed  Google Scholar 

  2. Hak AE, Karlson EW, Feskanich D, Stampfer MJ, Costenbader KH (2009) Systemic lupus erythematosus and the risk of cardiovascular disease: results from the nurses’ health study. Arthritis Rheum 61(10):1396–1402

    Article  PubMed Central  PubMed  Google Scholar 

  3. Solomon DH, Karlson EW, Rimm EB, Cannuscio CC, Mandl LA, Manson JE, Stampfer MJ, Curhan GC (2003) Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis. Circulation 107(9):1303–1307

    Article  PubMed  Google Scholar 

  4. Ward MM (1999) Premature morbidity from cardiovascular and cerebrovascular diseases in women with systemic lupus erythematosus. Arthritis Rheum 42(2):338–346

    Article  CAS  PubMed  Google Scholar 

  5. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial (2002). Lancet 360 (9326):7-22.

  6. Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, McKillop JH, Packard CJ (1995) Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med 333(20):1301–1307

    Article  CAS  PubMed  Google Scholar 

  7. Libby P (2002) Inflammation in atherosclerosis. Nature 420(6917):868–874

    Article  CAS  PubMed  Google Scholar 

  8. Schonbeck U, Libby P (2004) Inflammation, immunity, and HMG-CoA reductase inhibitors: statins as antiinflammatory agents? Circulation 109(21 Suppl 1):II18–II26

    PubMed  Google Scholar 

  9. Abeles AM, Pillinger MH (2006) Statins as antiinflammatory and immunomodulatory agents: a future in rheumatologic therapy? Arthritis Rheum 54(2):393–407

    Article  CAS  PubMed  Google Scholar 

  10. Meroni PL, Luzzana C, Ventura D (2002) Anti-inflammatory and immunomodulating properties of statins. An additional tool for the therapeutic approach of systemic autoimmune diseases? Clin Rev Allergy Immunol 23(3):263–277

    Article  CAS  PubMed  Google Scholar 

  11. Jury EC, Isenberg DA, Mauri C, Ehrenstein MR (2006) Atorvastatin restores Lck expression and lipid raft-associated signaling in T cells from patients with systemic lupus erythematosus. J Immunol 177(10):7416–7422

    Article  CAS  PubMed  Google Scholar 

  12. McCarey DW, McInnes IB, Madhok R, Hampson R, Scherbakov O, Ford I, Capell HA, Sattar N (2004) Trial of Atorvastatin in Rheumatoid Arthritis (TARA): double-blind, randomised placebo-controlled trial. Lancet 363(9426):2015–2021

    Article  CAS  PubMed  Google Scholar 

  13. Vollmer T, Key L, Durkalski V, Tyor W, Corboy J, Markovic-Plese S, Preiningerova J, Rizzo M, Singh I (2004) Oral simvastatin treatment in relapsing-remitting multiple sclerosis. Lancet 363(9421):1607–1608

    Article  CAS  PubMed  Google Scholar 

  14. Jury EC, Ehrenstein MR (2005) Statins: immunomodulators for autoimmune rheumatic disease? Lupus 14(3):192–196

    Article  CAS  PubMed  Google Scholar 

  15. Lawman S, Mauri C, Jury EC, Cook HT, Ehrenstein MR (2004) Atorvastatin inhibits autoreactive B cell activation and delays lupus development in New Zealand black/white F1 mice. J Immunol 173(12):7641–7646

    Article  CAS  PubMed  Google Scholar 

  16. Graham KL, Lee LY, Higgins JP, Steinman L, Utz PJ, Ho PP (2008) Failure of oral atorvastatin to modulate a murine model of systemic lupus erythematosus. Arthritis Rheum 58(7):2098–2104

    Article  CAS  PubMed  Google Scholar 

  17. Abud-Mendoza C, de la Fuente H, Cuevas-Orta E, Baranda L, Cruz-Rizo J, Gonzalez-Amaro R (2003) Therapy with statins in patients with refractory rheumatic diseases: a preliminary study. Lupus 12(8):607–611

    Article  CAS  PubMed  Google Scholar 

  18. de Kruif MD, Limper M, Hansen HR, de Ruiter J, Spek CA, van Gorp EC, ten Berge IJ, Rowshani AT, ten Cate H, Meesters EW (2009) Effects of a 3-month course of rosuvastatin in patients with systemic lupus erythematosus. Ann Rheum Dis 68(10):1654

    Article  PubMed  Google Scholar 

  19. Costenbader KH, Liang MH, Chibnik LB, Aizer J, Kwon H, Gall V, Karlson EW (2007) A pravastatin dose-escalation study in systemic lupus erythematosus. Rheumatol Int 27(11):1071–1077

    Article  CAS  PubMed  Google Scholar 

  20. Petri MA, Kiani AN, Post W, Christopher-Stine L, Magder LS (2011) Lupus Atherosclerosis Prevention Study (LAPS). Ann Rheum Dis 70(5):760–765

    Article  CAS  PubMed  Google Scholar 

  21. Iranian Registry of Clinical Trials (2012) Comparison the efficacy of atorvastatin with placebo on disease activity in patients with systemic lupus erythematosus. http://www.irct.ir/.

  22. Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40(9):1725

    Article  CAS  PubMed  Google Scholar 

  23. Gladman DD, Ibanez D, Urowitz MB (2002) Systemic lupus erythematosus disease activity index 2000. J Rheumatol 29(2):288–291

    PubMed  Google Scholar 

  24. Ferreira GA, Navarro TP, Telles RW, Andrade LE, Sato EI (2007) Atorvastatin therapy improves endothelial-dependent vasodilation in patients with systemic lupus erythematosus: an 8 weeks controlled trial. Rheumatology (Oxford) 46(10):1560–1565

    Article  CAS  Google Scholar 

  25. Ridker PM, Rifai N, Clearfield M, Downs JR, Weis SE, Miles JS, Gotto AM Jr (2001) Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med 344(26):1959–1965

    Article  CAS  PubMed  Google Scholar 

  26. Ridker PM, Rifai N, Pfeffer MA, Sacks F, Braunwald E (1999) Long-term effects of pravastatin on plasma concentration of C-reactive protein. The Cholesterol and Recurrent Events (CARE) Investigators. Circulation 100(3):230–235

    Article  CAS  PubMed  Google Scholar 

  27. Albert MA, Danielson E, Rifai N, Ridker PM (2001) Effect of statin therapy on C-reactive protein levels: the pravastatin inflammation/CRP evaluation (PRINCE): a randomized trial and cohort study. JAMA 286(1):64–70

    Article  CAS  PubMed  Google Scholar 

  28. Ridker PM, Rifai N, Lowenthal SP (2001) Rapid reduction in C-reactive protein with cerivastatin among 785 patients with primary hypercholesterolemia. Circulation 103(9):1191–1193

    Article  CAS  PubMed  Google Scholar 

  29. Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, Glynn RJ (2008) Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 359(21):2195–2207

    Article  CAS  PubMed  Google Scholar 

  30. Kwak B, Mulhaupt F, Myit S, Mach F (2000) Statins as a newly recognized type of immunomodulator. Nat Med 6(12):1399–1402

    Article  CAS  PubMed  Google Scholar 

  31. Bianchi S, Bigazzi R, Caiazza A, Campese VM (2003) A controlled, prospective study of the effects of atorvastatin on proteinuria and progression of kidney disease. Am J Kidney Dis 41(3):565–570

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

This study was supported by the grant of Isfahan University of Medical Sciences with the reference number of 390369.

Disclosures

None.

Author information

Authors and Affiliations

  1. Department of Rheumatology, Alzahra Hospital, Isfahan University of Medical Sciences, Isfahan, 8174675731, Iran

    Alimohammad Fatemi & Zahra Sayedbonakdar

  2. Department of Internal Medicine, Alzahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran

    Mahdi Moosavi & Mehdi Kazemi

  3. Department of Community Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

    Ziba Farajzadegan

  4. Department of Epidemiology, Isfahan University of Medical Sciences, Isfahan, Iran

    Abbas Smiley

Authors
  1. Alimohammad Fatemi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mahdi Moosavi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zahra Sayedbonakdar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ziba Farajzadegan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mehdi Kazemi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Abbas Smiley
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alimohammad Fatemi.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fatemi, A., Moosavi, M., Sayedbonakdar, Z. et al. Atorvastatin effect on systemic lupus erythematosus disease activity: a double-blind randomized clinical trial. Clin Rheumatol 33, 1273–1278 (2014). https://doi.org/10.1007/s10067-014-2654-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-014-2654-7

Keywords

Search

Navigation