Lupus Atherosclerosis Prevention Study (LAPS)

Background Cardiovascular disease is one of the major causes of death in systemic lupus erythematosus (SLE). A study was undertaken to investigate whether treatment with statins would reduce subclinical measures of atherosclerosis over a 2-year period. Methods 200 patients with SLE without clinical cardiovascular disease were randomised to receive atorvastatin 40 mg daily or an identical placebo. At baseline and after 2 years of follow-up, helical CT scanning (for coronary artery calcium) and carotid duplex (for intima media thickness/plaque) were performed. Patients were seen for measures of disease activity at 1 month, 3 months and quarterly thereafter. The primary outcome variable was change in coronary artery calcium. Results At baseline, 43% had coronary artery calcium. At 2 years there was no significant difference between the groups in progression of coronary artery calcium, carotid intima media thickness or carotid plaque. There was no significant difference between the groups in disease activity, measures of inflammation or endothelial cell activation. Conclusion This study provides no evidence that atorvastatin reduces subclinical measures of atherosclerosis or disease activity over 2 years in patients with SLE. In fact, it does not appear to reduce biochemical measures of inflammation. The anti-inflammatory effects of statins observed in the general population were not replicated in this SLE clinical trial. Clinicaltrials.gov (NCT 00120887).

[1]  M. Urowitz,et al.  The bimodal mortality pattern of systemic lupus erythematosus. , 1976, The American journal of medicine.

[2]  L. Kuller,et al.  Vascular imaging: changing the face of cardiovascular research , 2000, Lupus.

[3]  R. Devereux,et al.  Rate and determinants of progression of atherosclerosis in systemic lupus erythematosus. , 2007, Arthritis and rheumatism.

[4]  Hilla Peretz,et al.  Ju n 20 03 Schrödinger ’ s Cat : The rules of engagement , 2003 .

[5]  M. Ward.  Premature morbidity from cardiovascular and cerebrovascular diseases in women with systemic lupus erythematosus. , 1999, Arthritis and rheumatism.

[6]  T. Callister,et al.  Effect of HMG-CoA reductase inhibitors on coronary artery disease as assessed by electron-beam computed tomography. , 1998, The New England journal of medicine.

[7]  P. Ridker,et al.  C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. , 2000, The New England journal of medicine.

[8]  Paul Schoenhagen,et al.  Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial. , 2004, JAMA.

[9]  M. Ward,et al.  Mortality and causes of death in systemic lupus erythematosus , 2001, Current opinion in rheumatology.

[10]  M. Liang,et al.  A pravastatin dose-escalation study in systemic lupus erythematosus , 2007, Rheumatology International.

[11]  L. Magder,et al.  Coronary calcium in systemic lupus erythematosus is associated with traditional cardiovascular risk factors, but not with disease activity. , 2008, The Journal of rheumatology.

[12]  Neil J Stone,et al.  Implications of Recent Clinical Trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines , 2004, Circulation.

[13]  T. Roy,et al.  Simvastatin-induced lupus-like syndrome. , 2000, Tennessee medicine : journal of the Tennessee Medical Association.

[14]  M. Pfeffer,et al.  Long-term effects of pravastatin on plasma concentration of C-reactive protein. The Cholesterol and Recurrent Events (CARE) Investigators. , 1999, Circulation.

[15]  P. Meroni,et al.  Anti-inflammatory and immunomodulating properties of statins , 2002, Clinical reviews in allergy & immunology.

[16]  H. Silbershatz,et al.  Safety of atorvastatin derived from analysis of 44 completed trials in 9,416 patients. , 2003, The American journal of cardiology.

[17]  R. Madhok,et al.  Trial of Atorvastatin in Rheumatoid Arthritis (TARA): double-blind, randomised placebo-controlled trial , 2004, The Lancet.

[18]  Paul M. Ridker,et al.  Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. , 2001, The New England journal of medicine.

[19]  E. Tremoli,et al.  Statins prevent endothelial cell activation induced by antiphospholipid (anti-beta2-glycoprotein I) antibodies: effect on the proadhesive and proinflammatory phenotype. , 2001, Arthritis and rheumatism.

[20]  M. Verhaar,et al.  Premature atherosclerotic cardiovascular disease in systemic lupus erythematosus. , 2007, Arthritis and rheumatism.

[21]  N Rifai,et al.  Effect of statin therapy on C-reactive protein levels: the pravastatin inflammation/CRP evaluation (PRINCE): a randomized trial and cohort study. , 2001, JAMA.

[22]  Y. Arad,et al.  Treatment of asymptomatic adults with elevated coronary calcium scores with atorvastatin, vitamin C, and vitamin E: the St. Francis Heart Study randomized clinical trial. , 2005, Journal of the American College of Cardiology.

[23]  T. Callister,et al.  Aggressive Versus Moderate Lipid-Lowering Therapy in Hypercholesterolemic Postmenopausal Women: Beyond Endorsed Lipid Lowering With EBT Scanning (BELLES) , 2005, Circulation.

[24]  M. Petri,et al.  Comparison of different methods of classifying patients with systemic lupus erythematosus. , 1991, The Journal of rheumatology.

[25]  M. Abrahamowicz,et al.  Traditional Framingham risk factors fail to fully account for accelerated atherosclerosis in systemic lupus erythematosus. , 2001, Arthritis and rheumatism.

[26]  J F Fries,et al.  The 1982 revised criteria for the classification of systemic lupus erythematosus. , 1982, Arthritis and rheumatism.

[27]  P. Libby,et al.  Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. , 2008, The New England journal of medicine.

[28]  L. Kuller,et al.  Progression of carotid intima-media thickness and plaque in women with systemic lupus erythematosus. , 2008, Arthritis and rheumatism.

[29]  F. Paul,et al.  Oral High-Dose Atorvastatin Treatment in Relapsing-Remitting Multiple Sclerosis , 2008, PloS one.

[30]  Simone Appenzeller,et al.  Risk Factors in Cardiovascular Disease in Systemic Lupus Erythematosus , 2013, Current cardiology reviews.

[31]  M. Petri,et al.  Risk factors for coronary artery disease in patients with systemic lupus erythematosus. , 1992, The American journal of medicine.

[32]  Thomas Weber,et al.  Intensive versus moderate lipid lowering with statins after acute coronary syndromes. , 2004, The New England journal of medicine.

[33]  J. Schwartz,et al.  Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus. , 2003, The New England journal of medicine.

[34]  K. Nakashima,et al.  [The Rotterdam study]. , 2011, Nihon rinsho. Japanese journal of clinical medicine.

[35]  R. D'Agostino,et al.  Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study. , 1997, American journal of epidemiology.

[36]  L. Merle,et al.  Statins for multiple sclerosis , 2004, The Lancet.

[37]  Paolo Raggi,et al.  Premature coronary-artery atherosclerosis in systemic lupus erythematosus. , 2003, The New England journal of medicine.

[38]  淳一 佐々木.  Air Force/Texas Coronary Atherosclerosis Prevention Study , 2008 .

[39]  D. Gladman,et al.  Morbidity in systemic lupus erythematosus. , 1987, The Journal of rheumatology. Supplement.

[40]  M. Pfeffer,et al.  Long-Term Effects of Pravastatin on Plasma Concentration of C-reactive Protein , 1999 .

[41]  Mimi Y. Kim,et al.  Combined oral contraceptives in women with systemic lupus erythematosus. , 2005, The New England journal of medicine.

[42]  V. Durkalski,et al.  Oral simvastatin treatment in relapsing-remitting multiple sclerosis , 2004, The Lancet.

[43]  P. Ridker,et al.  Rapid Reduction in C-Reactive Protein With Cerivastatin Among 785 Patients With Primary Hypercholesterolemia , 2001, Circulation.

[44]  H. Wollersheim,et al.  Reproducibility of ultrasonographic measurements of different carotid and femoral artery segments in healthy subjects and in patients with increased intima-media thickness. , 1997, Clinical science.

[45]  A. Hofman,et al.  Reproducibility of carotid vessel wall thickness measurements. The Rotterdam Study. , 1994, Journal of clinical epidemiology.

[46]  R. Panizzon,et al.  Lupus-Like Syndrome Associated with Statin Therapy , 2004, Dermatology.