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Children as young as eight years old should be given statins, reported four newspapers (7 August 2007). The newspapers generally report results from a well-conducted randomised controlled trial accurately, although the authors stated that the optimal age for statin initiation is not known and further research is needed.

On 7th August 2007, four newspapers (1-4) reported that children with familial hypercholesterolemia (an inherited disorder causing high LDL-cholesterol levels and an increased risk of heart disease) should be given statins to reduce the risk of heart disease.
The research published in Circulation (5) was a small, but well-conducted RCT; 214 children with familial hypercholesterolemia were treated with pravastatin or placebo. At longer-term follow-up (children receiving placebo had received pravastatin for at least 2 years) total cholesterol, LDL-cholesterol and triglycerides were reduced from baseline levels (average: 22.5%, 29.2% and 1.9% respectively), and HDL-cholesterol increased by 3.1%. No serious adverse events were reported; none of the children discontinued treatment due to a laboratory adverse event.
The newspapers generally reported the research results accurately. All the newspapers stated that children as young as eight years should be given statins; researchers stated that the optimal age for statin initiation is unknown. The Daily express (2) stated that statins could routinely be given to all children with hypercholesterolemia; the study stated that children with familial hypercholesterolemia were to be targeted. Two newspapers highlighted the need for further research (1, 2).

Evaluation of the evidence base for the efficacy and safety of prescribing statins to children.

Where does the evidence come from?

The study was conducted by Dr Rodenburg and colleagues from several departments of the University of Amsterdam, The Netherlands. Funding was provided by Bristol-Myers Squibb.

What were the authors' objectives?

To evaluate the safety and efficacy of statin treatment in children, relating these to the age of statin initiation.

What was the nature of the evidence?

The report is the long-term follow up of a double blind randomised controlled trial (RCT) of 214 children with familial hypercholesterolemia (age range 8 to 18.5 years) comparing pravastatin with placebo (7). Of these, 28 children (13%) were lost to follow-up; 186 were included in the current study. The mean age of the 186 children was 13.7 (SD +/-3.1) years, and 49% were male. Children under the age of 14 years in the treatment arm received 20mg pravastatin, and children 14 years and over received 40mg. The trial lasted two years, after which children in the treatment arm continued on pravastatin, while children in the placebo arm were also prescribed pravastatin. Children were followed-up for at least two years after the completion of the original trial. The outcomes of interest were changes in carotid intima-media thickness (an indicator of the risk of cardiovascular disease), cholesterol and triglyceride levels, and adverse events.

What were the findings?

On average, statin treatment reduced total cholesterol from baseline by 22.5% (SD +/-15.2), LDL-cholesterol by 29.2% (SD +/-17.3), and triglycerides by 1.9% (IQR -27.2, 43.6). HDL-cholesterol increased from baseline by 3.1% (SD +/-21.8).

Regression analyses showed that combined carotid intima-media thickness and age at statin initiation, gender, and the duration of statin use, were all independent predictors of carotid IMT at follow-up. This implies that the younger that statin therapy is started, the smaller the increase in carotid intima-media thickness at follow-up.

No serious adverse events were reported; none of the children discontinued treatment due to a adverse event. Two boys had increased creatinine phosphokinase levels, four children complained of myalgia, three showed reduced levels of dehydroepiandosterone sulphate, and two children had increased adrenocorticotropic hormone levels.

What were the authors' conclusions?

Early initiation of statin treatment delays the progression of carotid intima-media thickness in adolescents and young adults with familial hypercholesterolemia.

How reliable are the conclusions?

The original RCT was well-conducted, with patients in the two groups being comparable at baseline in terms of important characteristics that could influence the results. However as all children received pravastatin for at least two years after the completion of the first RCT the long-term outcomes could not be measured as part of a placebo controlled trial. This may impact on the change from baseline results reported for the group of children as a whole. In addition, the power calculation used to recruit, was based on the short-term primary outcome, and numbers of participants fell below those stated as required during the follow-up period being evaluated in the current report. Despite this, the authors' results seem reliable, and the authors acknowledge that the optimal age of initiation of statin therapy is still unknown, and that further longer-term follow-up of children who receive early treatment is needed.

Systematic reviews

Information staff at CRD searched for systematic reviews relevant to this topic. Systematic reviews are valuable sources of evidence as they locate, appraise and synthesize all available evidence on a particular topic.

There were no related systematic reviews identified on the Cochrane Database of Systematic Reviews (CDSR), although there is one review which is currently being undertaken and will be available in the future (8). There were no related reviews on the Database of Abstracts of Reviews of Effects (DARE).