Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Does Atorvastatin Reduce Progression of Carotid Intimal Medial Thickening (CIMT) in Childhood SLE? Results from the Atherosclerosis Prevention in Pediatric Lupus (APPLE) Trial: A Multicenter, Randomized, Double-Blind Placebo-Controlled Study.
Schanberg3, Laura E., Sandborg4, Christy I., Barnhart3, Huiman X., Ardoin2, Stacy P., Yow3, Eric, Evans5, Gregory W., Mieszkalski3, Kelly L.
Childhood Arthitis and Rheumatology Research Alliance, New York, NY
Childhood Arthritis and Rheumatology Research Alliance, CARRA
Duke Univ Medical Center, Durham, NC
Stanford Medical Center, Stanford, CA
Wake Forest Univ
Wake Forest University
SLE patients are at markedly elevated risk for premature cardiovascular events. Given lifelong exposure to increased atherogenic potential, children and adolescents with SLE are ideal targets for prevention. Statins reduce cardiovascular morbidity and mortality in the general population, but their efficacy in preventing atherosclerosis progression in pediatric SLE is unknown.
Children and adolescents with SLE, aged 1021y, from 21 CARRA sites were randomized to receive atorvastatin (1020 mg based on weight) or placebo and followed for 3 years. All subjects met 1997 ACR criteria for SLE. Exclusion criteria included nephrotic syndrome, cholesterol >350, creatinine >2.5, CPK >3X nl or liver functions >2X normal. Background therapy included hydroxychloroquine, aspirin, folate, risk factor counseling, the AHA Therapeutic Lifestyle Changes diet, and routine SLE management. The primary endpoint was rate of progression of mean common CIMT, a surrogate marker for atherosclerosis, using a standardized ultrasound protocol read by a central core. Secondary endpoints included progression of mean maximal CIMT and lipid levels. The total sample size of 220 provided 8398% power to detect a 0.0045mm/y difference in mean-common CIMT progression rates between groups with an overall 0.05 type I error for several scenarios based on the estimated parameters for mean-mean common CIMT correlation of 0.6 between time points and SD (0.0380.047mm), dropout (11.623.1%), and compliance rate (7184%).
A total of 221 subjects were randomized between 9/0311/06 with 183 (83%) of them completing the trial. See table for baseline characteristics.
There were 138 SAEs with 7 considered related to study drug. Rhabdomyolysis was not reported. Database was locked on 6/21/10 and the final results of primary and secondary endpoints will be presented.
APPLE is an RCT designed to assess the safety and efficacy of atorvastatin in preventing progression of CIMT in pediatric SLE. APPLE represents the first RCT in pediatric SLE, the first CARRA clinical trial, and the longest study of statins in a pediatric cohort. Preliminary data demonstrate successful enrollment of the target population and completion of trial within study parameters. The data quality indicates that study results will determine whether use of statins in children and adolescents with SLE decreases CIMT progression and the risk of premature atherosclerosis.
To cite this abstract, please use the following information:
Schanberg, Laura E., Sandborg, Christy I., Barnhart, Huiman X., Ardoin, Stacy P., Yow, Eric, Evans, Gregory W., et al; Does Atorvastatin Reduce Progression of Carotid Intimal Medial Thickening (CIMT) in Childhood SLE? Results from the Atherosclerosis Prevention in Pediatric Lupus (APPLE) Trial: A Multicenter, Randomized, Double-Blind Placebo-Controlled Study. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1677