Metabolic and Atherosclerosis Research Center, Cincinnati, Ohio.
Rambam Health Care Campus, Haifa, Israel.
J Am Coll Cardiol. 2017 Aug 29;70(9):1162-1170. doi: 10.1016/j.jacc.2017.06.058.
Homozygous familial hypercholesterolemia (HoFH), a rare genetic disorder, is characterized by extremely elevated levels of low-density lipoprotein cholesterol (LDL-C) and accelerated atherosclerotic cardiovascular disease. Statin treatment starts at diagnosis, but no statin has been formally evaluated in, or approved for, HoFH children.
The authors sought to assess the LDL-C efficacy of rosuvastatin versus placebo in HoFH children, and the relationship with underlying genetic mutations.
This was a randomized, double-blind, 12-week, crossover study of rosuvastatin 20 mg versus placebo, followed by 12 weeks of open-label rosuvastatin. Patients discontinued all lipid-lowering treatment except ezetimibe and/or apheresis. Clinical and laboratory assessments were performed every 6 weeks. The relationship between LDL-C response and genetic mutations was assessed by adding children and adults from a prior HoFH rosuvastatin trial.
Twenty patients were screened, 14 randomized, and 13 completed the study. The mean age was 10.9 years; 8 patients were on ezetimibe and 7 on apheresis. Mean LDL-C was 481 mg/dl (range: 229 to 742 mg/dl) on placebo and 396 mg/dl (range: 130 to 700 mg/dl) on rosuvastatin, producing a mean 85.4 mg/dl (22.3%) difference (p = 0.005). Efficacy was similar regardless of age or use of ezetimibe or apheresis, and was maintained for 12 weeks. Adverse events were few and not serious. Patients with 2 defective versus 2 negative LDL receptor mutations had mean LDL-C reductions of 23.5% (p = 0.0044) and 14% (p = 0.038), respectively.
This first-ever pediatric HoFH statin trial demonstrated safe and effective LDL-C reduction with rosuvastatin 20 mg alone or added to ezetimibe and/or apheresis. The LDL-C response in children and adults was related to underlying genetic mutations. (A Study to Evaluate the Efficacy and Safety of Rosuvastatin in Children and Adolescents With Homozygous Familial Hypercholesterolemia [HYDRA]; NCT02226198).
家族性高胆固醇血症（HoFH）是一种罕见的遗传性疾病，其特征是低密度脂蛋白胆固醇（LDL-C）水平极高，动脉粥样硬化性心血管疾病进展迅速。他汀类药物治疗应在确诊后开始，但尚无他汀类药物在 HoFH 儿童中进行过正式评估或获得批准。
作者旨在评估瑞舒伐他汀在 HoFH 儿童中的 LDL-C 疗效，并研究其与潜在遗传突变的关系。
这是一项瑞舒伐他汀 20mg 与安慰剂对照、为期 12 周的随机、双盲、交叉研究，随后进行为期 12 周的瑞舒伐他汀开放标签治疗。患者停用所有降脂药物，仅保留依折麦布和/或血浆分离术。每 6 周进行一次临床和实验室评估。通过纳入之前 HoFH 瑞舒伐他汀试验中的儿童和成人患者，评估 LDL-C 应答与遗传突变的关系。
共筛选了 20 名患者，其中 14 名患者被随机分配，13 名患者完成了研究。患者的平均年龄为 10.9 岁；8 名患者服用依折麦布，7 名患者接受血浆分离术。安慰剂组的平均 LDL-C 为 481mg/dl（范围：229 至 742mg/dl），瑞舒伐他汀组为 396mg/dl（范围：130 至 700mg/dl），瑞舒伐他汀组的 LDL-C 降低了 85.4mg/dl（22.3%）（p=0.005）。无论年龄大小、是否使用依折麦布或血浆分离术，疗效均相似，且能维持 12 周。不良事件较少且不严重。与 LDL 受体突变 2 个阴性相比，2 个缺陷患者的 LDL-C 降低幅度分别为 23.5%（p=0.0044）和 14%（p=0.038）。
这是第一项 HoFH 儿童他汀类药物试验，证明瑞舒伐他汀单独或联合依折麦布和/或血浆分离术治疗可安全有效地降低 LDL-C。儿童和成人的 LDL-C 反应与潜在的遗传突变有关。[评估瑞舒伐他汀在杂合子家族性高胆固醇血症儿童和青少年中的疗效和安全性的研究（HYDRA）；NCT02226198]。
