Use of atorvastatin in systemic lupus erythematosus in children and adolescents.
Author(s): Schanberg LE, Sandborg C, Barnhart HX, Ardoin SP, Yow E, Evans GW, Mieszkalski KL, Ilowite NT, Eberhard A, Imundo LF, Kimura Y, von Scheven E, Silverman E, Bowyer SL, Punaro L, Singer NG, Sherry DD, McCurdy D, Klein-Gitelman M, Wallace C, Silver R, Wagner-Weiner L, Higgins GC, Brunner HI, Jung L, Soep JB, Reed AM, Provenzale J, Thompson SD
Affiliation(s): Duke University Medical Center, Durham, NC. email@example.com.
Publication date & source: 2011-10-26, Arthritis Rheum., [Epub ahead of print]
OBJECTIVE: Statins reduce atherosclerosis and cardiovascular morbidity in the general population, but their efficacy and safety in children and adolescents with systemic lupus erythematosus (SLE) are unknown. We sought to determine atorvastatin's 3-year efficacy and safety in preventing subclinical atherosclerosis progression in pediatric-onset SLE. METHODS: A total of 221 participants with pediatric SLE (10-21 years) from 21 North American sites were enrolled in APPLE, a double-blind, placebo-controlled, randomized clinical trial, between August 2003 and November 2006 with 36-month follow-up. Participants were randomized to receive atorvastatin (n= 113) or placebo (n= 108) at 10 or 20 mg/ day depending on weight, in addition to usual care. The primary endpoint was progression of mean-mean common carotid intima-medial thickening (CIMT) measured by ultrasound. Secondary endpoints included other segment/ wall-specific CIMT measures, lipid profile, high-sensitivity c-reactive protein (hsCRP), and SLE disease activity and damage outcomes. RESULTS: Progression of mean-mean common CIMT did not differ significantly between treatment groups (0.0010 [atorvastatin] vs. 0.0024 mm/ year [placebo], P= 0.24). The atorvastatin group achieved lower hsCRP (P= 0.04), total cholesterol (P<0.001), and low-density lipoprotein (P<0.001) levels compared with placebo. In the placebo group, CIMT progressed significantly (0.0023-0.0144 mm/ year, P<0.05) across all CIMT outcomes. Serious adverse events and critical safety measures did not differ between groups. CONCLUSIONS: Study results demonstrate no significant effect on subclinical atherosclerosis progression with routine statin use over 3 years in young SLE patients; however, further analyses may suggest subgroups that would benefit from targeted statin therapy. Atorvastatin was well tolerated without safety concerns. (c) 2011 American College of Rheumatology. Copyright (c) 2011 by the American College of Rheumatology.