Use of atorvastatin in systemic lupus erythematosus in children and adolescents.
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. This study was undertaken to determine the 3-year efficacy and safety of atorvastatin in preventing subclinical atherosclerosis progression in pediatric-onset SLE.


METHODS
A total of 221 participants with pediatric SLE (ages 10-21 years) from 21 North American sites were enrolled in the Atherosclerosis Prevention in Pediatric Lupus Erythematosus study, a randomized double-blind, placebo-controlled clinical trial, between August 2003 and November 2006 with 36-month followup. 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 end point was progression of mean-mean common carotid intima-media thickening (CIMT) measured by ultrasound. Secondary end points included other segment/wall-specific CIMT measures, lipid profile, high-sensitivity C-reactive protein (hsCRP) level, and SLE disease activity and damage outcomes.


RESULTS
Progression of mean-mean common CIMT did not differ significantly between treatment groups (0.0010 mm/year for atorvastatin versus 0.0024 mm/year for 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 across all CIMT outcomes (0.0023-0.0144 mm/year; P<0.05). Serious adverse events and critical safety measures did not differ between groups.


CONCLUSIONS
Our results indicate that routine statin use over 3 years has no significant effect on subclinical atherosclerosis progression in young SLE patients; however, further analyses may suggest subgroups that would benefit from targeted statin therapy. Atorvastatin was well tolerated without safety concerns.
Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA. schan001@mc.duke.edu
L E
LE
Schanberg
C
C
Sandborg
H X
HX
Barnhart
S P
SP
Ardoin
E
E
Yow
G W
GW
Evans
K L
KL
Mieszkalski
N T
NT
Ilowite
A
A
Eberhard
L F
LF
Imundo
Y
Y
Kimura
E
E
von Scheven
E
E
Silverman
S L
SL
Bowyer
M
M
Punaro
N G
NG
Singer
D D
DD
Sherry
D
D
McCurdy
M
M
Klein-Gitelman
C
C
Wallace
R
R
Silver
L
L
Wagner-Weiner
G C
GC
Higgins
H I
HI
Brunner
L
L
Jung
J B
JB
Soep
A M
AM
Reed
J
J
Provenzale
S D
SD
Thompson
D000293:Adolescent; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000150:complications / Q000175:diagnosis / Q000517:prevention & control*; D000069059:Atorvastatin; D059168:Carotid Intima-Media Thickness; D002648:Child; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D008055:Lipids / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008297:Male; D011758:Pyrroles / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D008055:Lipids; D011758:Pyrroles; D000069059:Atorvastatin