LDL APHERESIS: A New Treatment For Severe Dyslipidemia
Rama Shankar, M.D., Fellow
What can transfusion medicine offer to patients
with hypercholesterolemia? Recent advances in affinity column technology now enable the
efficient removal of LDL-cholesterol directly from the bloodstream by apheresis. This new
therapeutic tool may reduce the risk of progressive atherosclerotic disease in
hypercholesterolemic patients who are resistant to diet and drugs.
Hypercholesterolemia is a well known major risk factor for ischemic heart disease. Reduction in serum total cholesterol and the low-density lipoprotein-fraction, LDL-C, has been conclusively shown in randomized, controlled clinical trials to prevent the development and progression of atherosclerotic cardiovascular disease.
Lipids are transported in different lipoprotein fractions in blood. The protein moiety of the lipoprotein, apolipoprotein-B, and its degradation products, are the atherogenic elements. The apolipoprotein-B is in highest concentration in LDL-C and is present in smaller amounts in very low density lipoprotein-cholesterol (VLDL-C). High-density cholesterol (HDL-C) levels lack the atherogenic apolipoprotein-B component and relate inversely to coronary artery disease risk.
Familial hypercholesterolemia is an autosomal dominant disorder which results from mutations involving the gene encoding the LDL receptor. The rare homozygous form is characterized by premature atherosclerosis at a very young age (first 10 years of life); myocardial infarction-related mortality usually occurs by the age of 25 years. While not as severe, patients with the heterozygous form (frequency 1 in 500) are also at high risk for premature atherosclerotic disease.
Adequate control of serum cholesterol levels is generally achieved by dietary modifications and/or drug regimens, including HMG-CoA reductase inhibitors, bile acid binding resins, and nicotinic acid. However, a subset of patients, particularly those with familial hypercholesterolemia, fail to respond. Additional treatment methods may be necessary to reduce LDL-C to safer levels in these individuals who are at high risk for atherosclerotic disease complications.
Two extracorporeal procedures, plasmapheresis and LDL-apheresis, have been shown to be effective in lowering LDL-C. However, plasmapheresis has the disadvantage of non-selective removal of all serum proteins including the "protective" cholesterol-HDL-C. The LDL-apheresis procedure selectively removes apolipoprotein-B containing cholesterol such as LDL-C and VLDL-C, sparing the HDL-C.
Several methods for LDL-apheresis have been developed. However, the only device currently approved by the Food & Drug Administration is a dextran sulfate adsorption system (Liposorber LA-15Ô , Kaneka America Corp.). This procedure acutely lowers LDL, VLDL, and lipoprotein(a) levels by 60-70%. The time-averaged lowering of LDL falls in the range of 40-60% depending on how often the treatment is performed (usually every 1-2 weeks). A considerable degree of compliance on the part of the patient is necessary, since long-term treatment is usually indicated.
Lipoprotein-apheresis is a safe and well tolerated procedure. As with all apheresis procedures, adequate venous access is required. Complications are infrequent and consist of hypotension, bradycardia, nausea, and headache.
The efficacy of LDL-apheresis in lowering LDL-C and slowing the rate of atherosclerotic cardiovascular disease progression has been reported in a number of trials:
Overall, these studies show that using LDL-apheresis can achieve a substantial lipid lowering effect in all or nearly all patients with severe hypercholesterolemia. The reduction was obtained regardless of prior response to dietary and/or drug interventions. Also noted was a reduction in angina and stress test improvement which did not correlate with the angiographic regression of the lesions. The rationale for this observation may be the improvement in blood flow due to changes in blood viscosity or blood vessel wall reactivity. While the clinical responses have been quite favorable, long-term benefits such as a reduction in, or prevention of, coronary heart disease have not been conclusively demonstrated.
LDL-apheresis appears to be a safe and effective treatment for patients with hypercholesterolemia who are refractory to drug and/or dietary interventions. In addition to patients with homozygous FH, the FDA recently approved LDL-apheresis use in patients with coronary artery disease and LDL-C levels greater than 200 mg/dl. In patients with no coronary artery disease, apheresis is recommended if the LDL-C level is ³ 300 mg/dl.
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