ABC | Volume 111, Nº6, December 2018

Original Article Radaelli et al Statin treatment in children: meta-analysis Arq Bras Cardiol. 2018; 111(6):810-821 in HDL‑cholesterol levels (2.8%) was also statistically significant. 16 In the study comparing rosuvastatin versus placebo, changes in LDL-cholesterol, TC, and APOB levels were statistically significant compared to placebo for all three doses (5 mg, 10 mg, 20 mg) (p < 0.001). 19 Most of the studies included in this meta-analysis focused on the effect of statins on LDL. As seen in these results in children with FH, statins are effective in lowering LDL‑cholesterol and TC levels. The effectiveness of reducing the LDL-cholesterol and TC levels with statin treatment is consistent in all RCTs analyzed. The effects of statins on other levels of lipids, such as HDL-cholesterol and TG are not so consistent; that is why the results are not extrapolated to the entire pediatric population. Patients without FH must focus on changes in lifestyle first, before relying on a drug to improve their cholesterol levels. The included studies had essential elements that determine the quality of studies, which are important for the generation of evidence. Conducting a randomized controlled trial in the pediatric population is not as common as in adults. However, there is a lack of a recognized methodology to assess the quality of pediatric studies. That is the reason why we used the clinical testing format, as used in the adult population. The adverse event profile of a pharmacological agent is a particular concern in pediatric population. Thus, in general, data suggest that the risk of adverse events in children treated with statins are similar to those observed in adults treated with statin, at least in the short term. Studies evaluated the effect of statin therapy on clinical outcomes, hormonal status, biochemical measures of growth, nutrition and liver or kidney toxicity. For most of these parameters, there was no statistically significant difference between treatment and placebo groups. There were no reports of serious adverse events. Hepatic transaminase elevation and Creatine‑phosphokinase, which are of particular concern in adults, did not differ in the studied groups. Current guidelines for FH indicate pharmacological treatment in affected subjects between 8 to 10 years and in younger children only with extreme elevation of LDL‑cholesterol and associated risk factors, having risk for premature CAD. 30-33 Statins can be considered as first line treatment in children with HeFH and having an increase of LDL, after changes in diet and lifestyle. Response to treatment with statins should be assessed in 1 to 3 months after the start of therapy and periodically thereafter according to guidelines. 34 Children treated with statins should also be frequently monitored for adverse events (for example, hepatic transaminases, creatine kinase, liver enzymes) and statins are contraindicated during pregnancy. 34 There is also a need for further studies to evaluate the safety of these pediatric patients throughout their lives. The results for the growth and sexual development should be considered in children under 10 years of age. Future studies should seek to include pediatric patients with secondary forms of dyslipidemia and start examining the combination of therapy in children. However, we found some limitations in these studies. One of them is the duration of statin therapy in the included studies, which ranged from 8 to 104 weeks, whereas in the clinical practice, patients with FH are subjected to continue with statin treatment for the rest of their lives, once the therapy was initiated. 35 Another limitation of these studies is the conduction only in children with FH and children with secondary dyslipidemia were not included. 35 They also do not include information on the use of high doses of statins, such as those used in adults. Besides, the long-term efficacy data also are not available and remain unknown. Braamskamp et al. 36 published the first study evaluating hormonal concentrations of FH subjects before and 10 years after the start of treatment with statins, compared with their unaffected siblings, which minimizes genetic and environmental variation between groups. Their results demonstrated that the hormone concentrations in patients with FH are among the reference range compared to their unaffected siblings. Conclusion Based on the evidence available in this meta-analysis, statins significantly reduced LDL-cholesterol in children with HeFH. However, there is no data regarding long-term outcomes of both effectiveness and safety. Author contributions Conception and design of the research: Radaelli G, Pellanda LC; Acquisition of data: Radaelli G, Sausen G; Analysis and interpretation of the data: Radaelli G, Cesa CC, Pellanda LC; Statistical analysis: Radaelli G, Cesa CC; Writing of the manuscript: Radaelli G, Sausen G, Cesa CC, Santos FS; Critical revision of the manuscript for intellectual content: Portal VL, Neyeloff JL, Pellanda LC. Potential Conflict of Interest No potential conflict of interest relevant to this article was reported. Sources of Funding There were no external funding sources for this study. Study Association This article is part of the thesis of Doctoral submitted by Graciane Radaelli, from Programa de Pós Graduação - Fundação Universitária de Cardiologia (IC-FUC). Ethics approval and consent to participate This article does not contain any studies with human participants or animals performed by any of the authors. 816