Statin therapy fails to slow progression of atherosclerosis in pediatric lupus patients
Atorvastatin therapy was found to be ineffective in reducing atherosclerosis progression in children and adolescents with systemic lupus erythematosus (SLE). Results of the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) Trial, now available in Arthritis & Rheumatism, a journal published by Wiley-Blackwell on behalf of the American College of Rheumatology (ACR), report that the statin therapy did trend toward positive effect of treatment and may benefit patients with more severe SLE who were not included in the trial.
The ACR reports that SLE affects 322,000 adult Americans. Exact figures for pediatric SLE cases are difficult to establish, but the best estimate is that 5,000 to 10,000 children in the U.S. have lupus (Lehman 1996). One of the long-term complications of SLE for both adult and pediatric patients is accelerated atherosclerosis—a build-up of plaque in the aterial wall which can lead to heart attack and stroke. Medical evidence reports that SLE patients are up to 8 times more likely to develop premature coronary heart disease, compared to the general population. Women with lupus are 50 times more likely to have a heart attack than healthy premenopausal women.
“The prognosis for pediatric lupus patients has significantly improved over the last few decades, however diagnosis at an earlier age subjects these patients to greater cardiovascular risk from systemic disease activity and treatment side effects over a longer time period,” explains lead investigator, Dr. Laura Schanberg with the Department of Pediatrics at Duke University Medical Center in Durham, North Carolina. Previous studies show children with SLE have more severe organ damage, and longer exposure to illness and potentially toxic treatments compared with adults.
Prevalence of atherosclerosis in pediatric SLE is unknown, but precursors of the disease such as thickening of aterial artery walls as measured by carotid intima-media thickening (CIMT), have been reported. Statins have been shown to reduce atherosclerosis progression in adults, but have not been investigated in a pediatric SLE population. The APPLE Trial assessed 36-month therapy with atorvastatin, commercially known as Lipitor®, in 221 SLE patients between 10 and 21 years of age at 21 sites in North America. Participants were randomized, with 113 receiving treatment with atorvastatin and 108 a placebo at 10 or 20 mg/day (depending on weight). Researchers determined effectiveness of therapy by progression CIMT as measured by ultrasound.
“Our results demonstrate no significant effect on progression of atherosclerosis in children and adolescents with SLE who were treated with atorvastatin use over the 3-year period,” concluded Dr. Christy Sandborg from Stanford University School of Medicine in California and co-primary investigator of the Apple Trial. “Further study of subgroups of SLE patients that may benefit from statin therapy is warranted.” While ineffective in reducing progression of atherosclerosis in this study population, atorvastatin was determined to be safe and well tolerated.
In a related editorial also published today in Arthritis & Rheumatism, Dr. Angelo Ravelli from the 1Università degli Studi di Genova and Istituto di Ricovero e Cura a Carattere Scientifico in Italy said, “Although the APPLE Trial found atorvastatin to be ineffective in pediatric SLE patients with low to moderate disease activity, a trend toward positive effect was detected. This indicates that while statin therapy may not be necessary in all SLE patients, preventative statin therapy may benefit those with more severe disease activity.” Post-hoc subgroup analyses of the APPLE Trial are underway which may uncover those patient groups who may benefit from treatment with atorvastatin.
This study is published in Arthritis & Rheumatism. Media wishing to receive a PDF of the article may contact firstname.lastname@example.org.
“Use of Atorvastatin in Systemic Lupus Erythematosus in Children and Adolescents.” L. E. Schanberg, C. Sandborg, H. X. Barnhart, S. P. Ardoin, E. Yow, G. W. Evans, K. L. Mieszkalski, N. T. Ilowite, A. Eberhard, L. F. Imundo, Y. Kimura, E. von Scheven, E. Silverman, S. L. Bowyer, L. Punaro, N. G. Singer, D. D. Sherry, D. McCurdy, M. Klein-Gitelman, C. Wallace, R. Silver, L. Wagner-Weiner, G. C. Higgins, H. I. Brunner, L. Jung, J. B. Soep, A. M. Reed, J. Provenzale, and S. D. Thompson. Arthritis & Rheumatism; Published Online: Oct. 27, 2011 (DOI: 10.1002/art.30645). http://doi.wiley.com/10.1002/art.30645.
Editorial: “Should Children and Adolescents with Systemic Lupus Erythematosus be Given Statin Therapy to Prevent Early Atherosclerosis?” Angelo Ravelli. Arthritis & Rheumatism; Published Online: Oct. 27, 2011 (DOI: 10.1002/art.30642). http://doi.wiley.com/10.1002/art.30642.
About the Journal
Arthritis & Rheumatism is an official journal of the American College of Rheumatology (ACR) and the Association of Rheumatology Health Professionals (ARHP), a division of the College, and covers all aspects of inflammatory disease. The American College of Rheumatology (http://www.rheumatology.org) is the professional organization who share a dedication to healing, preventing disability, and curing the more than 100 types of arthritis and related disabling and sometimes fatal disorders of the joints, muscles, and bones. Members include practicing physicians, research scientists, nurses, physical and occupational therapists, psychologists, and social workers. For details, please visit http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1529-0131.
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ACR Annual Meeting Press Registration Now Open
Press registration is now open to journalists planning to attend the 2011 ACR/ARHP Annual Scientific Meeting in Chicago. Held November 4-9, the ACR/ARHP Annual Scientific Meeting is the premier meeting in rheumatology.
For more information, including to view the press conference schedule, visit http://www.rheumatology.org/education/annual/newsroom.asp. Follow the meeting on twitter by using the official hashtag: #ACR2011.
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