ABC | Volume 111, Nº6, December 2018

Original Article Statin Treatments And Dosages In Children With Familial Hypercholesterolemia: Meta-Analysis Graciane Radaelli, 1 Grasiele Sausen, 1 Claudia Ciceri Cesa, 1 Francisco de Souza Santos, 2 Vera Lucia Portal, 1 Jeruza Lavanholi Neyeloff, 1 Lucia Campos Pellanda 1 Instituto de Cardiologia - Fundação Universitária de Cardiologia – IC/FUC, 1 Porto Alegre, RS – Brazil Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), 2 Porto Alegre, RS – Brazil Mailing Address: Lucia Campos Pellanda • Av. Princesa Isabel, 370, 3º andar. Postal Code 99620-000, Santana, Porto Alegre, RS – Brazil E-mail: pellanda.pesquisa@gmail.com, metodologia.up@cardiologia.org.br Manuscript received February 20, 2018, revised manuscript May 15, 2018, accepted June 27, 2018 DOI: 10.5935/abc.20180180 Abstract Background: Children with familial hypercholesterolemia may develop early endothelial damage leading to a high risk for the development of cardiovascular disease (CVD). Statins have been shown to be effective in lowering LDL cholesterol levels and cardiovascular events in adults. The effect of statin treatment in the pediatric population is not clearly demonstrated. Objective: To systematically review the literature to evaluate the effects of different statins and dosages in total cholesterol levels in children and adolescents with familial hypercholesterolemia. We also aimed to evaluate statin safety in this group. Methods: PubMed, EMBASE, Bireme, Web of Science, Cochrane Library, SciELOand LILACS databases, were searched for articles published from inception until February 2016. Two independent reviewers performed the quality assessment of the included studies. We performed a meta-analysis with random effects and inverse variance, and subgroup analyses were performed. Results: Ten trials involving a total of 1543 patients met the inclusion criteria. Our study showed reductions in cholesterol levels according to the intensity of statin doses (high, intermediate and low): (-104.61 mg/dl, -67.60 mg/dl, -56.96 mg/dl) and in the low-density lipoprotein cholesterol level: [-105.03 mg/dl (95% CI -115.76, -94.30), I2 19.2%], [-67.85 mg/dl (95% CI -83.36, -52.35), I2 99.8%], [-58.97 mg/dl (95% CI -67.83, -50.11), I2 93.8%. The duration of statin therapy in the studies ranged from 8 to 104 weeks, precluding conclusions about long-term effects. Conclusion: Statin treatment is efficient in lowering lipids in childrenwith FH. There is need of large, long-termand randomized controlled trials to establish the long-term safety of statins. (Arq Bras Cardiol. 2018; 111(6):810-821) Keywords: Statins; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia Type II/genetic; Children; Meta-Analysis. Introduction Familial hypercholesterolemia (FH) is a dominant autosomal genetic disease. The worldwide prevalence is of 1 in 250 people affected with the heterozygous form (HeFH) of HF. 1 FH is characterized by high levels of low-density lipoprotein (LDL) cholesterol due the reduced hepatic capacity to remove LDL-cholesterol from blood circulation, 2 which can result in early atherosclerosis development. 3 Further, children with FH have damage in the endothelial function and increased intima‑media thickness (IMT) 4 indicating early atherogenesis. The hydroxy-methyl-glutaryl-CoA (HMG-CoA) reductase inhibitors or statins decrease the coronary morbidity and mortality in high-risk adults. They have proven to be effective in decreasing LDL-cholesterol levels and cardiovascular events in adults. 5 Statins are one of the most prescribed drugs in the world 6 for adults and, in usual doses, are notably safe. The expert consensus recommends drug treatment for children older than 10 years old with LDL-cholesterol level ≥ 5 mmol/L (190 mg/dl), whose cholesterol levels remain elevated despite diet measures during the period from 8 weeks to 2 years for children ages 8–18 years. It is also considered the treatment for those with LDL-cholesterol ≥ 4 mmol/L (160 mg/dl) with the presence of two or more cardiovascular risk factors or family history of CVD. 2,7 The US Food and Drug Administration (FDA) 8 has approved the use of some statins like simvastatin, atorvastatin, fluvastatin, pravastatin, rosuvastatin and lovastatin for pediatric and adolescent patients. Pravastatin is approved for use at 8 years of age, other statins are approved for use from 10 years on . FDA 8 recommends statins for children with FH, primary or genetic dyslipidemia. The treatment to reduce cholesterol levels in pediatric patients is based on evidence involving only adults. 9 The effect of statins in pediatric population has been limited to short-term randomized clinical trials (RCTs). 10,11 Thus, the aim of this study was to systematically review the literature to evaluate the effects of different statins and the dosages in elevated plasma levels of total cholesterol (TC), LDL- cholesterol and apolipoprotein B (APOB) and in decreased high-density lipoprotein (HDL) cholesterol levels in children and adolescents with FH. We also aimed to evaluate statin safety in this group. 810