Long-term statin therapy normalized the progression of carotid intima-media thickness in a Dutch study of children with familial hypercholesterolemia, according to a research letter to the editor published online Sept. 9 in JAMA.
Guidelines for treatment of this disorder in children advise the initiation of statin therapy as early as 8 years of age, but long-term efficacy and safety data for treatment initiated in childhood "do not exist," said Dr. D. Meeike Kusters of the department of vascular medicine, Academic Medical Center, Amsterdam, and her associates.
In the late 1990s, the investigators performed a double-blind cohort study in which 214 children aged 8-18 years who were heterozygous for familial hypercholesterolemia were randomly assigned to receive either pravastatin or placebo and were followed for 2 years. They found significant regression of carotid intima-media thickness with active treatment. All of the study participants were then offered treatment and were followed for 10 years, along with their unaffected siblings.
Dr. Kusters and her associates now report the findings from that follow-up of 194 study participants (of whom 163 still use statins) and 83 of their siblings, who now are all aged 18-30 years. Progression of carotid intima-media thickness was similar between the two groups, indicating that statins normalized this progression in affected patients over the long term. Moreover, earlier statin initiation correlated with thinner carotid intima-media thickness a decade later, the researchers said (JAMA 2014:312;1055-7).
No serious adverse events were reported, although three patients discontinued statin therapy because of adverse events. Laboratory safety measures did not differ between patients with familial hypercholesterolemia who took the drugs and their siblings, and there were no differences between the two groups in growth, maturation, or educational attainment. This small study, however, lacked the statistical power to detect rare events.
Despite this beneficial effect, the patients’ LDL-cholesterol levels "did not meet current treatment standards," the investigators wrote, and their carotid intima-media thickness remained greater than that of their unaffected siblings throughout the trial. "More robust lipid-lowering therapy or earlier initiation of statins may be required to completely restore arterial wall morphology and avert cardiovascular events later in life in this high-risk population," Dr. Kusters and her associates added.
This study was supported by the Dutch Heart Foundation. Dr. Kusters reported no financial conflicts of interest; one of her associates reported receiving lecture fees from Aegerion, Amgen, AstraZeneca, Eli Lilly, Genzyme, ISIS, Merck Sharp Dohme, Novartis, Pfizer, Regeneron, Roche, and Sanofi.