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Incorporation of Low-Density Lipoprotein Apheresis into the Treatment Program of Patients With Severe Hypercholesterolemia

Current Atherosclerosis Reports
2000;2:308-313.

Bruce R. Gordon, MD

At the time this article was written, there were several modes of LDL-apheresis available:

LDL-apheresis using columns containing antibodies or dextran sulfate cellulose:
- involves perfusion of plasma through a column containing poly- or monoclonal antibodies to adsorb apolipoprotein-B–containing lipoproteins (apoB)
- regarding dextran sulfate cellulose, specific adsorption of apoB is achieved via charge attraction of the matrix for the lipoprotein
LDL-apheresis using the heparin-induced method:
- positively charged LDL-C and other ß-lipoproteins bound by heparin at low pH
- specifically removes LDL-C, VLDL-C, Lp(a), and fibrinogen with little removal of HDL-C or other plasma proteins
LDL-apheresis using double membrane filtration:
- selective process based on the ability of a secondary membrane to discriminate between plasma LDL-C and Lp(a) and smaller molecules
LDL-apheresis using direct adsorption of lipoproteins blood perfusion system:
- negatively charged, immobilized, modified polyacrylate gel binds positively charged apoB by electrostatic interaction
Lipoprotein(a) apheresis:
- immunoadsorption system that utilizes Lp(a)-specific antibodies

Observations of clinical improvement with minimal angiographic changes in patients with atherosclerosis suggest that LDL-apheresis may have beneficial effects in addition to lowering LDL-C. These effects may be due to improved blood rheology, improved coronary microcirculation, lower oxidized LDL-C levels, removal of VLDL-C and down-regulation of inflammatory processes.

The clinical benefits of LDL-apheresis have been demonstrated in numerous studies, including the HELP LDL-Apheresis Multicenter Study, the LDL-Apheresis Atherosclerosis Regression Study (LAARS), the German Multicenter LDL-Apheresis Trial, and the Familial Hypercholesterolemia (FH) Regression Study. LAARS demonstrated that the addition of biweekly LDL-apheresis to treatment with simvastatin improved regional myocardial perfusion, myocardial ischemia, and peripheral vascular disease. LDL-apheresis has been used to successfully treat hypercholesterolemic patients following heart transplant and patients with elevated Lp(a) levels undergoing coronary angioplasty. Data from the United States indicate that LDL-apheresis has decreased the number of clinical events in patients with coronary heart disease (CHD) by 48%. This is substantiated by a study in which the rate of coronary events in CHD patients with heterozygous (hz) FH was decreased from 72% to 10% when LDL-apheresis was added to drug therapy. Portocaval shunting has been used in some hmFH patients to obtain further reductions in LDL-C. Furthermore, LDL-apheresis may provide an alternative to liver transplantation in individuals with hmFH.

The author concludes that incorporating LDL-apheresis into treatment is beneficial in patients with refractory hypercholesterolemia and CHD.

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