TREATMENT OF FAMILIAL HYPERCHOLESTEROLEMIA BY DEXTRAN SULFATE APHERESIS

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Patients with familial hypercholesterolemia (FH) type IIa are at high risk of premature coronary artery disease due to elevated low-density lipoprotein (LDL) and lipoprotein a [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 homozygotus patients 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, Kaneka, Japan) removed LDL and Lp(a) without lowering albumin levels, thus allowing return of autologous plasma without the need for colloid replacement solutions. Furthermore, high-density lipoprotein (HDL), a lipid moiety with highly protective effects against cardiovascular disease, increased over time. Three homozygous and three heterozygous FH patients were enrolled at the Clinical Center; 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%, respectively, in homozygotes and 61%, 76%, and 65%, respectively, in heterozygotes. Time-averaged levels of LDL cholesterol were reduced 53% (from 447 to 310 mg/dl) in homozygous FH patients and 41% (from 243 to 143 mg/dl) in heterozygous patients. The treatments were very well tolerated. An adverse association between using angiotensin converting enzyme (ACE) inhibitors and the development of flushing and hypotension was noted, and ACE inhibitor therapy is now routinely discontinued for at least 24 hours prior to each procedure. 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 the advantages, compared with simple plasma exchange, of eliminating the need for colloid replacement solutions and increasing HDL levels. 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 follow-up on an "LDL- Apheresis Registry" to gather post-licensure data on the effect of long- term treatment on the development of primary and secondary atherosclerotic events, and on overall survival.