Abstract
Statin medications have been suggested for widespread use in patients with systemic lupus erythematosus (SLE). We studied the dose effectiveness and tolerability of pravastatin in SLE. We compared 41 SLE subjects in a two-month open-label dose-titration study of pravastatin to 22 SLE controls. Lipids, ALT, CPK, CRP, adverse effects were assessed. Linear mixed models assessed changes in lipids and CRP, comparing pravastatin subjects to controls. After 1 month of pravastatin 10 mg a day, total cholesterol decreased by 16% (±12.1%) and LDL by 24% (±17%), compared with 1.8% (±7.5%) and 2.6% (±8.6%) decreases in controls (P < 0.001). CRP did not decline. Glucocorticoids appeared to decrease pravastatin effectiveness. Serum CPK increased in one subject. Pravastatin reduced LDL and total cholesterol levels approximately the same degree observed in normal individuals, but the effect appeared blunted in those on modest doses of glucocorticoids and those with higher BMI.
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Jonsson H, Nived O, Sturfelt G (1989) Outcome in systemic lupus erythematosus: a prospective study of patients from a defined population. Medicine (Baltimore) 68(3):141–150
Abu-Shakra M, Urowitz MB, Gladman DD et al (1995) Mortality studies in systemic lupus erythematosus. Results from a single center. I. Causes of death. J Rheumatol 22(7):1259–1264
Ward M (1999) Premature morbidity from cardiovascular and cerebrovascular diseases in women with systemic lupus erythematosus. Arthritis Rheum 42:338–346
Manzi S, Meilahn EN, Rairie JE et al (1997) Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study. Am J Epidemiol (145):408–415
Petri M, Perez-Gutthann S, Spence D et al (1992) Risk factors for coronary artery disease in patients with systemic lupus erythematosus. Am J Med 93(5):513–519
Rahman P, Urowitz MB, Gladman DD et al (1999) Contribution of traditional risk factors to coronary artery disease in patients with systemic lupus erythematosus. J Rheumatol 26(11):2363–2368
Esdaile JM, Abrahamowicz M, Grodzicky T et al (2001) Traditional Framingham risk factors fail to fully account for accelerated atherosclerosis in systemic lupus erythematosus. Arthritis Rheum 44(10):2331–2337
Roman MJ, Salmon JE, Sobel R et al (2001) Prevalence and relation to risk factors of carotid atherosclerosis and left ventricular hypertrophy in systemic lupus erythematosus and antiphospholipid antibody syndrome. Am J Cardiol 87(5):663–666 (A11)
Asanuma Y, Oeser A, Shintani AK et al (2003) Premature coronary-artery atherosclerosis in systemic lupus erythematosus. N Engl J Med 349(25):2407–2415
Roman MJ, Shanker BA, Davis A et al (2003) Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus. N Engl J Med 349(25):2399–2406
ALLHAT-LLT (2002) Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT-LLT) Jama 288(23):2998–3007
Shepherd J, Cobbe SM, Ford I et al (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
Simes J, Furberg CD, Braunwald E et al (2002) Effects of pravastatin on mortality in patients with and without coronary heart disease across a broad range of cholesterol levels. The Prospective Pravastatin Pooling project. Eur Heart J 23(3):207–215
White HD, Simes RJ, Anderson NE et al (2000) Pravastatin therapy and the risk of stroke. N Engl J Med 343(5):317–326
Nissen SE, Nicholls SJ, Sipahi I et al (2006) Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. Jama 295(13):1556–1565
Masumoto A, Hirooka Y, Hironaga K et al (2001) Effect of pravastatin on endothelial function in patients with coronary artery disease (cholesterol-independent effect of pravastatin). Am J Cardiol 88(11):1291–1294
Mason JC, Ahmed Z, Mankoff R et al (2002) Statin-induced expression of decay-accelerating factor protects vascular endothelium against complement-mediated injury. Circ Res 91(8):696–703
Lieberman EH, Gerhard MD, Uehata A et al (1996) Flow-induced vasodilation of the human brachial artery is impaired in patients <40 years of age with coronary artery disease. Am J Cardiol 78(11):1210–1214
Giri S, Parke AL, Waters DD (1998) Controlling cardiovascular risk factors in systemic lupus erythematosus. J Musculoskel Med 15:42–52
Aranow C, Ginzler EM (2000) Coronary artery disease in SLE: high suspicion leads to early recognition. J Musculoskel Med 17:473–482
Urowitz MB, Gladman DD (2000) How to improve morbidity and mortality in systemic lupus erythematosus. Rheumatology (Oxford) 39(3):238–244
Salmon JE, Roman MJ (2001) Accelerated atherosclerosis in systemic lupus erythematosus: implications for patient management. Curr Opin Rheumatol 13(5):341–344
Noel B (2004) Risks and benefits of statins in lupus erythematosus. Arch Intern Med 164(1):107–108
Bruce IN (2005) Cardiovascular disease in lupus patients: should all patients be treated with statins and aspirin? Best Pract Res Clin Rheumatol 19(5):823–838
Petri M, Kiani AN, Post W et al (2006) Lupus atherosclerosis prevention study (LAPS): a randomized double blind placebo controlled trial of atorvastatin versus placebo (abstract). Arthritis Rheum 90S(54)
Castelao AM, Grinyo JM, Castineiras MJ et al (1995) Effect of pravastatin in the treatment of hypercholesterolemia after renal transplantation under cyclosporine and prednisone. Transplant Proc 27(4):2217–2220
Kobashigawa JA, Katznelson S, Laks H et al (1995) Effect of pravastatin on outcomes after cardiac transplantation. N Engl J Med 333(10):621–627
Tan EM, Cohen AS, Fries JF et al (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25(11):1271–1277
Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40(9):1725
Aizer J, Karlson EW, Chibnik LB et al (2006) A controlled comparison of brachial artery flow mediated dilation (FMD) and digital pulse amplitude tonometry (PAT) in the assessment of endothelial function in systemic lupus erythematosus (abstract). Arthritis Rheum (in press)
Liang MH, Socher SA, Roberts WN et al (1988) Measurement of systemic lupus erythematosus activity in clinical research. Arthritis Rheum 31(7):817–825
Lennernas H, Fager G (1997) Pharmacodynamics and pharmacokinetics of the HMG-CoA reductase inhibitors. Similarities and differences. Clin Pharmacokinet 32(5):403–425
Knopp RH (1999) Drug treatment of lipid disorders. N Engl J Med 341(7):498–511
Maron DJ, Fazio S, Linton MF (2000) Current perspectives on statins. Circulation 101(2):207–213
Vaughan CJ, Gotto AM Jr, Basson CT (2000) The evolving role of statins in the management of atherosclerosis. J Am Coll Cardiol 35(1):1–10
Chong PH, Seeger JD, Franklin C (2001) Clinically relevant differences between the statins: implications for therapeutic selection. Am J Med 111(5):390–400
Shishov M, Koneru S, Houk JL et al (2005) The medication adherence self-report inventory (MASRI) can accurately measure adherence with medications in SLE (abstract). Arthritis Rheum 53:S424
Kwak B, Mulhaupt F, Myit S et al (2000) Statins as a newly recognized type of immunomodulator. Nat Med 6(12):1399-1402
Kanda H, Hamasaki K, Kubo K et al (2002) Antiinflammatory effect of simvastatin in patients with rheumatoid arthritis. J Rheumatol 29(9):2024–2026
McCarey DW, McInnes IB, Madhok R et al (2004) Trial of Atorvastatin in Rheumatoid Arthritis (TARA): double-blind, randomised placebo-controlled trial. Lancet 363(9426):2015–2021
Hedman M, Neuvonen PJ, Neuvonen M et al (2004) Pharmacokinetics and pharmacodynamics of pravastatin in pediatric and adolescent cardiac transplant recipients on a regimen of triple immunosuppression. Clin Pharmacol Ther 75(1):101–109
Butani L (2005) Prospective monitoring of lipid profiles in children receiving pravastatin preemptively after renal transplantation. Pediatr Transplant 9(6):746–753
Acknowledgments
The authors thank Dr. Marie Gerhard-Herman for her efforts on behalf of our SLE studies in the General Clinical Research Center and Danielle Blanch for her assistance with data management.
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Supported by NIH grants P60 AR47782, R0149880 and K24 AR052401, the Kirkland Scholar Fellowship, Arthritis Foundation/American College of Rheumatology Arthritis Investigator Award, Rheuminations and a 50th Anniversary Scholars in Medicine Award from Harvard Medical School.
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Costenbader, K.H., Liang, M.H., Chibnik, L.B. et al. A pravastatin dose-escalation study in systemic lupus erythematosus. Rheumatol Int 27, 1071–1077 (2007). https://doi.org/10.1007/s00296-007-0341-6
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DOI: https://doi.org/10.1007/s00296-007-0341-6