TREATMENT OF FAMILIAL HYPERCHOLESTEROLEMIA BY DEXTRAN SULFATE APHERESIS

家族性高胆固醇血症（FH）患者有高风险， 低密度脂蛋白升高致早发性冠状动脉疾病 (LDL)和Lp（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不应答 接受治疗 硫酸葡聚糖亲和法选择性去除LDL 在一项多中心协作研究中， 美国study. 硫酸葡聚糖单采系统（Liposorber LA-15 Kanegafuchi，日本）去除LDL和Lp（a），而不影响HDL或白蛋白 浓度，从而允许自体血浆的返回并避免 需要胶体替代溶液。 两个纯合子和两个 杂合子FH患者在临床中心入组; 在全国范围内招募的队列包括10个纯合子和54个杂合子。 该研究现已完成，并关闭进一步招募患者， 虽然那些已经取得文件证明的好处， 在豁免的基础上继续LDL单采治疗， FDA，正在申请器械许可证。 给药7至14天 的间隔总胆固醇、LDL和Lp（a）胆固醇的平均急性降低 在纯合子中分别为70%，81%和68%，在纯合子中分别为61%，76%， 在杂合子中，分别为65%和65%。 LDL的时间平均水平 纯合子FH患者胆固醇降低53%（447至310 mg/dL） 杂合子型为41%（243 ~ 143 mg/dL）。 治疗效果很好 耐受性良好，无明显不良反应发生。 我们的数据表明，硫酸葡聚糖吸附是一种安全有效的 一种清除血浆中LDL胆固醇的方法，与 简单的血浆置换，无需胶体置换 解决方案和促进更有益的LDL/HDL胆固醇比率。 本研究中使用的试验用器械的IDE编号为 G880069; IDE保持器为Kaneka America。

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.