***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVES This study was undertaken to evaluate the efficacy and safety of rosuvastatin therapy for children with familial hypercholesterolemia . BACKGROUND Familial hypercholesterolemia is a common inherited disorder causing markedly elevated low-density lipoprotein cholesterol ( LDL-C ) levels from birth and result ing in premature atherosclerosis . In children , statins have been shown to be effective in reducing LDL-C , restoring flow-mediated dilation , and slowing carotid intima-media thickening . However , few children in these trials achieved current LDL-C goals . METHODS This study comprised a 12-week double-blind , r and omized , placebo-controlled trial , followed by a 40-week open-label , titration-to- goal extension phase in 177 pubertal children , ages 10 to 17 years , with familial hypercholesterolemia . Participants were r and omly assigned to placebo or rosuvastatin 5 , 10 , or 20 mg once daily . RESULTS Compared with placebo , rosuvastatin 5 , 10 , and 20 mg reduced LDL-C by 38 % , 45 % , and 50 % , respectively ( p < 0.001 for each group vs. placebo ) . With a maximum allowed dose of 20 mg , 40 % achieved the treatment goal of < 110 mg/dl during the open-label , titration-to- goal phase . Rosuvastatin was well tolerated , with no apparent adverse impact on growth or development . CONCLUSIONS In children with familial hypercholesterolemia , rosuvastatin 20 mg daily reduced LDL-C by 50 % . Nonetheless , only 40 % attained the consensus LDL-C target of < 110 mg/dl , reflecting these patients ' high baseline LDL-C levels ( mean , 232 mg/dl ) . ( Pediatric Lipid-Reduction Trial of Rosuvastatin [ PLUTO ] ; NCT00355615 ) OBJECTIVES The study evaluated the efficacy and safety of long-term coadministration of ezetimibe and simvastatin in adolescents with heterozygous familial hypercholesterolemia ( HeFH ) . BACKGROUND Aggressive intervention to achieve lipid goals for adolescents with HeFH is recommended to reduce risk of premature cardiovascular disease . METHODS In a multicenter , r and omized , double-blind , placebo-controlled study , 248 male and female subjects ages > or=10 and < or=17 years with HeFH were r and omized to receive : step 1 : simvastatin 10 , 20 , or 40 mg/day plus ezetimibe 10 mg/day or placebo for 6 weeks , followed by step 2 : simvastatin 40 mg/day plus ezetimibe 10 mg/day or placebo for 27 weeks ; followed by step 3 : all subjects received open-label simvastatin 10 or 20 mg/day ( titrated to maximum 40 mg/day ) plus ezetimibe 10 mg/day for 20 weeks . Safety was assessed throughout the study . RESULTS Coadministered ezetimibe and simvastatin for 6 weeks ( step 1 ) result ed in significantly greater mean reduction in low-density lipoprotein cholesterol ( LDL-C ) from baseline ( 49.5 % ) compared with simvastatin monotherapy ( 34.4 % ; p < 0.01 ) in pooled dose groups and in individual dose groups ( 46.7 % vs. 30.4 % , 49.5 % vs. 34.3 % , 52.1 % vs. 38.6 % , respectively ; p < 0.01 ) . At 33 weeks ( step 2 ) , ezetimibe-simvastatin subjects had a mean 54.0 % reduction in LDL-C compared with a mean 38.1 % reduction in simvastatin monotherapy subjects ( p < 0.01 ) . At 53 weeks ( step 3 ) , the pooled reduction in LDL-C was 49.1 % . All treatment regimens were well tolerated throughout 53 weeks . CONCLUSIONS Coadministration of ezetimibe with simvastatin was safe , well tolerated , and provided higher LDL-C reduction compared with simvastatin alone in adolescents with HeFH studied up to 53 weeks . ( Effects of Ezetimibe With Simvastatin in the Therapy of Adolescents With Heterozygous Familial Hypercholesterolemia ; NCT00129402 ) Objective . The present study was design ed to evaluate the lipid-altering efficacy , safety , and tolerability of lovastatin treatment in adolescent girls with heterozygous familial hypercholesterolemia . Methods . A total of 54 postmenarchal girls , aged 10 to 17 years , were enrolled in a 24-week , double-blind , r and omized , placebo-controlled study . After a 4-week diet/placebo run-in period , patients were r and omized to 1 of 2 groups : ( 1 ) treatment with diet plus lovastatin 20 mg/day for 4 weeks , followed by diet plus lovastatin 40 mg/day for 20 weeks , or ( 2 ) diet plus placebo for 24 weeks . Results . Baseline values of lipids , lipoproteins , and apolipoproteins ( apo ) were comparable between treatment groups . Lovastatin treatment was efficacious at reducing low-density lipoprotein cholesterol by 23 % to 27 % , total cholesterol by 17 % to 22 % , and apo B by 20 % to 23 % at weeks 4 and 24 , respectively . Between-treatment group differences were not statistically significant for triglycerides , very-low-density lipoprotein cholesterol , high-density lipoprotein cholesterol , or apo A-I.  Lovastatin was generally safe and well tolerated . There were no clinical ly significant alterations in vital signs ( blood pressure and pulse rate ) , anthropomorphic measurements ( height , weight , and BMI ) , hormone levels ( luteinizing hormone , follicle-stimulating hormone , dehydroepi and rosterone sulfate , estradiol , and cortisol ) , menstrual cycle length , or tests of liver and muscle function . Conclusions . Lovastatin offers an efficacious and well-tolerated treatment option for improving lipid profiles in adolescent girls with familial hypercholesterolemia Background —A multicenter , r and omized , double-blind , placebo-controlled study was conducted to evaluate LDL cholesterol – lowering efficacy , overall safety , and tolerability and the influence on growth and pubertal development of simvastatin in a large cohort of boys and girls with heterozygous familial hypercholesterolemia ( heFH ) . Methods and Results —A total of 173 heFH children ( 98 boys and 75 girls ) were included in this study . After a 4-week diet/placebo run-in period , children with heFH were r and omized to either simvastatin or placebo in a ratio of 3:2 . Simvastatin was started at 10 mg/d and titrated at 8-week intervals to 20 and then 40 mg/d . During a 24-week extension period , the patients continued to receive simvastatin ( 40 mg ) or placebo according to their assignment . After 48 weeks of simvastatin therapy , there were significant reductions of LDL cholesterol ( −41 % ) , total cholesterol ( −31 % ) , apolipoprotein B ( −34 % ) , VLDL cholesterol ( −21 % ) , and triglyceride ( −9 % ) levels . HDL cholesterol and apolipoprotein A-I levels were increased by 3.3 % and 10.4 % , respectively ( not significant ) . No safety issues became evident . Except for small decreases in dehydroepi and rosterone sulfate compared with placebo , there were no significant changes from baseline in adrenal , gonadal , and pituitary hormones in either treatment group . Conclusions —Simvastatin significantly reduced LDL cholesterol , total cholesterol , triglyceride , VLDL cholesterol , and apolipoprotein B levels and was well tolerated in children with heFH . There was no evidence of any adverse effect of simvastatin on growth and pubertal development . Therefore , simvastatin at doses up to 40 mg is a well-tolerated and effective therapy for heFH children Rationale : Familial hypercholesterolemia ( FH ) predisposes patients to premature cardiovascular disease , with the process of atherosclerosis initiated in early childhood . Objective : As part of an ongoing trial to assess the efficacy and safety of rosuvastatin in children with FH aged 6 to 17 years , we report the differences in carotid intima-media thickness ( cIMT ) at baseline between children with FH and their unaffected siblings . Methods and Results : B-mode ultrasound measurements of the carotid artery were made in 196 children with FH and 64 of their siblings . Mean ( ±SE ) cIMT in children with FH was significantly greater than that of unaffected siblings ( 0.398±0.052 versus 0.377±0.045 mm ; P<0.001 ) . A significantly greater cIMT value was observed before the age of 8 years . Multivariable analyses showed that age , male sex , and presence of FH were independent predictors of cIMT . Conclusions : The difference in mean cIMT between children with FH and their unaffected siblings may be significant as early as age 8 years . This study confirms the need for early cholesterol lowering in this high-risk population . These patients participating in a carefully monitored study will help assess the long-term efficacy on cIMT and safety of statin therapy in young children CONTEXT Heterozygous familial hypercholesterolemia ( HeFH ) is a common disorder associated with early coronary artery disease , especially in men . The age at which drug therapy should be started is still controversial , as is the use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ( statins ) . OBJECTIVE To assess the lipid-lowering efficacy , biochemical safety , and effect on growth and sexual development of lovastatin in adolescent boys with HeFH . DESIGN One-year , double-blind , placebo-controlled , balanced , 2-period , 2-arm r and omized trial . In the first period ( 24 weeks ) , lovastatin was increased at 8 and 16 weeks and the dosage remained stable during the second period ( 24 weeks ) . The study was conducted between 1990 and 1994 . SETTING Fourteen pediatric outpatient clinics in the United States and Finl and . PATIENTS Boys aged 10 to 17 years with HeFH . Of 132 r and omized subjects ( 67 intervention , 65 placebo ) , 122 ( 63 intervention , 59 placebo ) and 110 ( 61 intervention , 49 placebo ) completed the first and second periods , respectively . INTERVENTION Lovastatin , starting at 10 mg/d , with a forced titration at 8 and 16 weeks to 20 and 40 mg/d , respectively , or placebo . MAIN OUTCOME MEASURES The primary efficacy outcome measure was low-density lipoprotein cholesterol ( LDL-C ) . Primary safety measures were growth and sexual development . RESULTS Compared with placebo , LDL-C levels of patients receiving lovastatin decreased significantly ( P<.001 ) by 17 % , 24 % , and 27 % receiving dosages of 10 , 20 , and 40 mg/d , respectively , and remained 25 % lower than baseline at 48 weeks . Growth and sexual maturation assessed by Tanner staging and testicular volume were not significantly different between the lovastatin and placebo groups at 24 weeks ( P = .85 ) and 48 weeks ( P = .33 ) ; neither were serum hormone levels or biochemical parameters of nutrition . However , the study was underpowered to detect significant differences in safety parameters . Serum vitamin E levels were reduced with lovastatin treatment consistent with reductions in LDL-C , the major carrier of vitamin E in the circulation . CONCLUSIONS This study in adolescent boys with HeFH confirmed the LDL-C-reducing effectiveness of lovastatin . Comprehensive clinical and biochemical data on growth , hormonal , and nutritional status indicated no significant differences between lovastatin and placebo over 48 weeks , although further study is required CONTEXT Children with familial hypercholesterolemia have endothelial dysfunction and increased carotid intima-media thickness ( IMT ) , which herald the premature atherosclerotic disease they develop later in life . Although intervention therapy in the causal pathway of this disorder has been available for more than a decade , the long-term efficacy and safety of cholesterol-lowering medication have not been evaluated in children . OBJECTIVE To determine the 2-year efficacy and safety of pravastatin therapy in children with familial hypercholesterolemia . DESIGN R and omized , double-blind , placebo-controlled trial that recruited children between December 7 , 1997 , and October  
    Output:
    
Statins were well-tolerated , with no significant differences in transaminase and creatine kinase levels or other adverse effects  compared with placebo .
Statins exerted no effect on growth or sexual development  .
Statins are quite effective in reducing TC , LDL-C , TG and apo-B and increasing HDL-C concentrations in children and adolescents with FH .
No safety issues were seen with statin use