TREATMENT OF FAMILIAL HYPERCHOLESTEROLEMIA BY DEXTRAN SULFATE APHERESIS

家族性高胆固醇血症（FH）患者有高风险， 早期冠状动脉疾病由于低密度升高 脂蛋白（LDL）和Lp（a）胆固醇水平。 饮食和药物治疗 可以降低大多数患者的胆固醇浓度 杂合子FH，但杂合子的比例很小，几乎所有 纯合子对治疗没有反应。 选择性去除LDL 在这些患者中评价了硫酸葡聚糖亲和吸附， 美国多中心协作研究。 硫酸葡聚糖 系统（Liposorber LA 015 Kanegafuchi，日本）去除LDL和Lp（a） 而不影响HDL或白蛋白浓度，从而允许返回 自体血浆和避免胶体置换的需要 解决方案 3例纯合子和3例杂合子FH患者， 在临床中心入组;全国入组的总队列 其中纯合子10例，杂合子54例。 该研究现已 完成并关闭患者的进一步招募，尽管这些 已获得有记录的益处的人被允许继续使用低密度脂蛋白- 在FDA批准的豁免基础上进行单采治疗， 设备许可证。 给药间隔为7至14天。 总胆固醇、LDL和Lp（a）胆固醇水平的平均急性降低为 纯合子分别为70%、81%和68%， 分别在杂合子中。 LDL的时间平均水平 在纯合子FH中胆固醇降低53%（447至310 mg/dL） 在杂合子患者中为41%（243至143 mg/dL）。 的 治疗耐受性良好，无明显不良反应 发生了。 我们的数据表明，硫酸葡聚糖吸附是一种安全， 有效清除血浆中LDL胆固醇的方法，并具有优点， 与简单的血浆置换相比， 胶体替代溶液和促进更有益的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 LA015 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. Three homozygous and three 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.