University of Chicago, Pritzker School of Medicine, Chicago, IL 60611, USA.
Clin Ther. 2013 Aug;35(8):1247-52. doi: 10.1016/j.clinthera.2013.06.014. Epub 2013 Jul 31.
Familial hypercholesterolemia (FH) is a common autosomal co-dominant genetic disorder that results in severely increased levels of LDL-C. Patients with FH are at an increased risk for premature coronary artery disease. Expert panels therefore recommend initiation of lipid-lowering therapy in childhood to reduce the very high lifetime risk of coronary artery disease. The bile acid sequestrant colesevelam is indicated to reduce elevated LDL-C levels in adults with primary hyperlipidemia and in boys and postmenarchal girls (aged 10-17 years) with heterozygous FH.
The purpose of this article was to review currently available data on the use of colesevelam in the treatment of heterozygous FH.
PubMed and Google Scholar were searched to identify clinical trials evaluating colesevelam in patients with heterozygous FH.
The search returned 2 results (both multicenter, multinational studies): 1 study conducted in adults and the other in pediatric patients. In the study in adults with refractory FH, the addition of colesevelam to a maximally tolerated regimen of a statin plus ezetimibe provided a significantly greater reduction from baseline in LDL-C levels compared with placebo. Significantly greater reductions from baseline in LDL-C were also seen in pediatric patients with heterozygous FH receiving colesevelam (alone or in combination with statins) compared with placebo. Colesevelam was generally well tolerated in studies in patients with FH; consistent with other colesevelam studies, gastrointestinal disorders were the most common drug-related adverse events, but these events rarely led to study withdrawal.
Currently available data demonstrate that colesevelam, alone or in combination therapy, is efficacious and well tolerated in the treatment of heterozygous FH in adults and pediatric patients, supporting its use as a treatment option in both of these patient populations.
家族性高胆固醇血症（FH）是一种常见的常染色体共显性遗传疾病，导致 LDL-C 水平显著升高。FH 患者发生早发性冠状动脉疾病的风险增加。因此，专家小组建议在儿童时期开始降脂治疗，以降低冠状动脉疾病的终身极高风险。胆酸螯合剂考来维仑被批准用于降低原发性高脂血症成人以及杂合子 FH 的男孩和初潮后女孩（10-17 岁）的升高的 LDL-C 水平。
本文旨在综述考来维仑治疗杂合子 FH 的现有数据。
检索 PubMed 和 Google Scholar，以鉴定评估考来维仑在杂合子 FH 患者中的临床试验。
检索结果有 2 项（均为多中心、多国研究）：1 项研究在成人中进行，另 1 项在儿科患者中进行。在难治性 FH 成人研究中，与安慰剂相比，考来维仑联合最大耐受剂量他汀类药物加依折麦布治疗可使 LDL-C 水平从基线显著降低。杂合子 FH 儿科患者接受考来维仑（单独或与他汀类药物联合）治疗也可使 LDL-C 水平从基线显著降低。在 FH 患者的研究中，考来维仑总体上耐受性良好；与其他考来维仑研究一致，胃肠道疾病是最常见的药物相关不良事件，但这些事件很少导致研究退出。
现有数据表明，考来维仑单独或联合治疗在成人和儿科患者杂合子 FH 的治疗中有效且耐受良好，支持其在这两种患者人群中作为治疗选择。
