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Atherosclerosis begins in childhood with the formation of fatty streaks. Early plaques can be found in adolescence and early coronary disease can be found in young adults. It has been suggested that early treatment may lead to great benefits in later life. This article is a narrative review of the role of lipid-lowering drug therapy in paediatric practice. Increased rates of atherosclerosis are known to occur in children with familial hypercholesterolaemia (FH), especially in homozygotes. There is evidence for the efficacy and safety of lipid-lowering therapies in children, particularly with respect to the effects of HMG-CoA reductase inhibitors (statins) on lipids and, to a limited extent, on other surrogate measures of atherosclerosis in patients with FH. Diagnosis of FH and its early treatment are recommended in all guidelines. Lipid-lowering drug therapy is recommended for the treatment of homozygous FH at all ages and from as young as 10 years of age for the treatment of heterozygous FH when there is a family history of very premature coronary heart disease (occurring at age <40 years). Controversy exists about other possible indications. Increased rates of atherosclerosis are seen in autoimmune disorders, including type 1 diabetes mellitus, systemic lupus erythematosus and Kawasaki's disease, and in transplant recipients. All evidence in these areas is derived by extrapolation from studies in adults. These disorders can be divided into those for which percutaneous coronary intervention is performed early and/or for which drugs used to treat the primary disorder increase the rate of atherosclerosis, and those for which this is not the case. In both cardiac transplantation and Kawasaki's disease, increased atherosclerosis can occur as a result of (i) disease-related vasculopathy; or (ii) increased restenosis secondary to interventions. Statins have a good evidence base for reducing rates of re-occlusion following coronary artery procedures, and this justifies their use in these settings. In renal transplantation, statins may have a role to play in patients with persistent dyslipidaemia and additional cardiovascular risk factors. In other disorders, such as type 1 diabetes, the disease process is atherogenic and thus statins may be justified in patients with a long history of disease (>10 years), poor control, and evidence of vascular or endothelial damage or additional cardiovascular risk factors. There is a role for lipid-lowering therapies in children at high risk of atherosclerosis, but the evidence base outside of FH is weak. Lipid-lowering therapy should be prescribed to all children with homozygous or severe heterozygous FH. Based on adult evidence, statin therapy should be considered in patients who have undergone coronary artery procedures or received cardiac transplants, in whom their primary role is to prevent vascular re-occlusion. In diseases associated with a chronic increased atherogenic risk, such as type 1 diabetes, statins should be considered in high-risk cases where additional cardiovascular risk factors are present. At present, the most important need is for trials to be performed in children using accepted surrogate endpoints to define whether lipid-lowering drug therapy is beneficial in this group.

作者:Anthony S, Wierzbicki;Adie, Viljoen

来源:Drug safety 2010 年 33卷 2期

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作者:
Anthony S, Wierzbicki;Adie, Viljoen
来源:
Drug safety 2010 年 33卷 2期
Atherosclerosis begins in childhood with the formation of fatty streaks. Early plaques can be found in adolescence and early coronary disease can be found in young adults. It has been suggested that early treatment may lead to great benefits in later life. This article is a narrative review of the role of lipid-lowering drug therapy in paediatric practice. Increased rates of atherosclerosis are known to occur in children with familial hypercholesterolaemia (FH), especially in homozygotes. There is evidence for the efficacy and safety of lipid-lowering therapies in children, particularly with respect to the effects of HMG-CoA reductase inhibitors (statins) on lipids and, to a limited extent, on other surrogate measures of atherosclerosis in patients with FH. Diagnosis of FH and its early treatment are recommended in all guidelines. Lipid-lowering drug therapy is recommended for the treatment of homozygous FH at all ages and from as young as 10 years of age for the treatment of heterozygous FH when there is a family history of very premature coronary heart disease (occurring at age <40 years). Controversy exists about other possible indications. Increased rates of atherosclerosis are seen in autoimmune disorders, including type 1 diabetes mellitus, systemic lupus erythematosus and Kawasaki's disease, and in transplant recipients. All evidence in these areas is derived by extrapolation from studies in adults. These disorders can be divided into those for which percutaneous coronary intervention is performed early and/or for which drugs used to treat the primary disorder increase the rate of atherosclerosis, and those for which this is not the case. In both cardiac transplantation and Kawasaki's disease, increased atherosclerosis can occur as a result of (i) disease-related vasculopathy; or (ii) increased restenosis secondary to interventions. Statins have a good evidence base for reducing rates of re-occlusion following coronary artery procedures, and this justifies their use in these settings. In renal transplantation, statins may have a role to play in patients with persistent dyslipidaemia and additional cardiovascular risk factors. In other disorders, such as type 1 diabetes, the disease process is atherogenic and thus statins may be justified in patients with a long history of disease (>10 years), poor control, and evidence of vascular or endothelial damage or additional cardiovascular risk factors. There is a role for lipid-lowering therapies in children at high risk of atherosclerosis, but the evidence base outside of FH is weak. Lipid-lowering therapy should be prescribed to all children with homozygous or severe heterozygous FH. Based on adult evidence, statin therapy should be considered in patients who have undergone coronary artery procedures or received cardiac transplants, in whom their primary role is to prevent vascular re-occlusion. In diseases associated with a chronic increased atherogenic risk, such as type 1 diabetes, statins should be considered in high-risk cases where additional cardiovascular risk factors are present. At present, the most important need is for trials to be performed in children using accepted surrogate endpoints to define whether lipid-lowering drug therapy is beneficial in this group.