Treatment Of Familial Hypercholesterolemia By Dextran Sulfate Apheresis

Clinical Center

Investigators

Abstract

The dextran sulfate apheresis system (Liposorber LA-15, Kaneka, Japan) was found to remove LDL and Lp(a) cholesterol without lowering HDL or albumin levels, thus avoiding the need for colloid replacement solutions. Six FH patients at the Clinical Center in the multicenter Liposorber Trial; the total cohort enrolled nationwide included 10 homozygotes and 54 heterozygotes. Treatments were administered at 7 to 14 day intervals. Mean acute reductions in total, LDL, and Lp(a) cholesterol levels were 70, 81, and 68 percent, respectively, in homozygotes and 61, 76, and 65 percent respectively, in heterozygotes. The treatments were very well tolerated. The results of the multicenter study suggest that dextran sulfate adsorption is a safe and effective way to clear plasma of LDL cholesterol, and has advantage, compared to simple plasma exchange, of eliminating the need for colloid replacement solutions. The data gathered in this study were used as the basis for licensure of the LA-15 system, which was approved by the FDA for treatment of FH in July 1996. Patients are now continuing long-term followup on an LDL-Apheresis Registry to gather post-licensure data on the effect of long-term treatment on development of primary and secondary atherosclerotic events, and on overall survival. A 5-year interim analysis of 49 of the original 64 patients who received long-term LDL-apheresis was performed. There was a 44 percent reduction in cardiovascular events during the 5 years the patients received LDL-apheresis compared with the 5-year period prior to LDL apheresis (3.5 events per 1,000 patient-months of treatment compared with 6.3 events per 1,000 patient-months before LDL-apheresis therapy). These findings support the long-term safety and clinical efficacy of LDL apheresis in patients with FH who are inadequately controlled with drug therapy. Two patients continue to receive regular biweekly LDL apheresis treatments at the Clinical Center. One of these two subjects is likely to be the oldest living survivor in the world with this disorder, and has undergone biweekly apheresis therapy for the past 29 years at the NIH.