TREATMENT OF FAMILIAL HYPERCHOLESTEROLEMIA BY DEXTRAN SULFATE APHERESIS

家族性高胆固醇血症(FH)患者患 低密度脂蛋白升高致早发冠状动脉疾病 (低密度脂蛋白)和脂蛋白(A)胆固醇水平。饮食和药物治疗，可以减少 大多数杂合子FH患者的胆固醇浓度，但 一小部分杂合子和几乎所有纯合子都没有反应 去接受治疗。葡聚糖硫酸酯亲和作用选择性去除低密度脂蛋白 在一项多中心协作性研究中，对这些患者进行了吸附评估。 美国留学。葡聚糖硫酸盐分离系统(Liposorber LA-15 Kanegafuchi，日本)去除低密度脂蛋白和Lp(A)而不影响高密度脂蛋白或白蛋白 浓缩，从而允许自体血浆返回并避免 需要胶体替代解决方案。两个纯合子和两个 杂合子FH患者在临床中心登记； 在全国范围内纳入的队列包括10个纯合子和54个杂合子。 这项研究现在已经完成，并结束了对更多患者的研究， 尽管那些已经获得记录利益的人被允许 在豁免的基础上继续进行低密度脂蛋白分离治疗 FDA，正在等待设备许可证。疗程为7-14天 间隔时间。总胆固醇、低密度脂蛋白和脂蛋白(A)胆固醇的平均急剧下降 纯合子的水平分别为70%、81%和68%， 在杂合子中分别为65%和65%。低密度脂蛋白的时间平均水平 纯合子FH患者胆固醇降低53%(447至310 mg/dL) 杂合子41%(243~143 mg/dL)。治疗效果很好 耐受性良好，未发生明显不良反应。 我们的数据表明，硫酸葡聚糖吸附是安全有效的 清除血浆中低密度脂蛋白胆固醇的方法，与 简单的血浆置换，不需要胶体置换 解决方案，并促进更有益的低密度脂蛋白/高密度脂蛋白胆固醇比率。 本研究中使用的调查设备的IDE编号为 G880069；IDE持有者是美国卡内卡。

Patients with familial hypercholesterolemia (FH) are at high risk of premature coronary artery disease due to elevated low density lipoprotein (LDL) and Lp(a) cholesterol levels. Diet and drug therapy, can reduce cholesterol concentrations in most patients with heterozygous FH, but a small proportion of heterozygous and nearly all homozygotes do not respond to therapy. Selective removal of LDL by dextran sulfate affinity adsorption was evaluated in these patients in a collaborative multicenter U.S. study. The dextran sulfate apheresis system (Liposorber LA-15 Kanegafuchi, Japan) removed LDL and Lp(a) without affecting HDL or albumin concentrations, thus allowing return of autologous plasma and avoiding the need for colloid replacement solutions. Two homozygous and two heterozygous FH patients were enrolled at the Clinical Center; the total cohort enrolled nationwide included 10 homozygotes and 54 heterozygotes. The study is now complete and closed to further accrual of patients, although those having achieved documented benefit are permitted to continue LDL-apheresis treatments on an exemption basis granted by the FDA, pending device licensure. Treatments were administered 7 to 14 day intervals. Mean acute reductions in total, LDL, and Lp(a) cholesterol levels were 70%, 81% and 68%, respectively, in homozygotes and 61%, 76%, and 65%, respectively, in heterozygotes. Time-averaged levels of LDL cholesterol were reduced 53% (447 to 310 mg/dL) in homozygous FH patients and 41% (243 to 143 mg/dL) in heterozygous ones. The treatments were well tolerated and no significant adverse reactions occurred. Our data suggest that dextran sulfate adsorption is a safe and effective way to clear plasma of LDL cholesterol, and has advantages, compared to simple plasma exchange, of eliminating the need for colloid replacement solutions and promoting a more beneficial LDL/HDL cholesterol ratio. The IDE number for the investigational device used in this study is G880069; the IDE holder is Kaneka America.