According to the American College of Rheumatology (ACR) 322,000 adult Americans are affected by systemic lupus erythematosus (SLE) with approximately 5,000 to 10,000 children in the U.S. affected by lupus (Lehman 1996), although exact figures for pediatric SLE cases remain difficult to establish. One of the long-term complications of SLE in both adult and pediatric patients is accelerated atherosclerosis, a build-up of plaque in the arterial wall leading to heart attack and stroke.
Although Atorvastatin therapy was established as being ineffective in reducing atherosclerosis progression in children and adolescents with SLE, results of a trial revealed in Arthritis & Rheumatism, a journal published by Wiley-Blackwell on behalf of the ACR, that statin therapy showed a positive trend towards effective treatment in people with more severe SLE who were not included in the Apple trial (Atherosclerosis Prevention in Pediatric Lupus Erythematosus trial).
According to medical evidence, SLE patients tend to have an eight-times higher risk of developing premature coronary heart disease than the general population. Compared to healthy pre-menopausal women, those with lupus have a 50-times higher potential risk of suffering a heart attack.
Lead researcher Dr. Laura Schanberg with the Department of Pediatrics at Duke University Medical Center in Durham, North Carolina states:
"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."
Earlier studies established that compared to adults, children with SLE have more severe organ damage, longer exposure to illness and potentially toxic treatments.
Although the prevalence of atherosclerosis in pediatric SLE is unknown, scientists have reported precursors of the disease, such as thickening of artery walls measured by carotid intima-media thickening (CIMT). In adults with SLE it has been shown that statins reduce atherosclerosis progression, however, this has not yet been investigated in pediatric SLE patients.
The APPLE Trial was a randomized, multi-center trial (21 North American sites) conducted in 221 SLE patients aged between 10 and 21 years to examine atorvastatin, commercially known as Lipitor®. Researchers randomized the participants, with 113 participants receiving atorvastatin therapy and 108 participants receiving either 10 or 20 mg of placebo daily depending on weight over a 36-month study period. The effectiveness of the therapy was determined by progression of CIMT measured by ultrasound.
Co-lead investigator of the Apple Trial, Dr. Christy Sandborg from the Stanford University School of Medicine in California summarized:
"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. Further study of subgroups of SLE patients that may benefit from statin therapy is warranted."
Although atorvastatin proved ineffective in reducing progression of atherosclerosis in this study population, it was determined to be safe and well tolerated.
Dr. Angelo Ravelli from the Università degli Studi di Genova and Istituto di Ricovero e Cura a Carattere Scientifico in Italy wrote in a related editorial also published this week in Arthritis & Rheumatism, that:
"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."
At present, post-hoc subgroup analyses of the APPLE Trial are underway that may reveal those patient groups who could benefit from atorvastatin therapy.
Written by Petra Rattue