Low‐Density Lipoprotein Apheresis for Prevention and Regression of Atherosclerosis: Clinical Results

Abstract

Hypercholesterolemia can be adequately controlled by appropriate diet and maximum lipid lowering drug therapy in most patients. Nevertheless, there exists a group of patients, including those with familial hypercholesterolemia (FH), who remain at high risk for the development or progression of premature coronary heart disease (CHD). For these patients additional measures such as surgery and low-density lipoprotein (LDL) apheresis have to be considered. The objective of this multicenter trial, which included 30 clinical centers (28 in Germany and one each in Scotland and Luxembourg), was to determine if repeated LDL apheresis using the Liposorber LA-15 system (Kaneka Corporation, Osaka, Japan) could lead to an additional acute and time averaged lowering of total cholesterol (TC) and LDL-cholesterol (LDL-C) in severely hypercholesterolemic patients whose cholesterol levels could not be controlled by appropriate diet and maximum drug therapy. A total of 6,798 treatments were performed on 120 patients, including 8 with homozygous FH, 75 with heterozygous FH, and 37 with unclassified FH or other hyperlipidemias from 1988 through 1994. The mean TC and mean LDL-C levels at baseline were 410.0 mg/dl and 333.9 mg/dl, respectively. LDL apheresis was performed once a week or at least once every 2 weeks in all patients. During treatment with the Liposorber system the mean acute percentage reduction was 52.6% for TC and 63.1% for LDL-C. Very low density lipoprotein cholesterol (VLDL-C) and triglycerides (TG) were also substantially reduced to 60.6% and 47.5%, respectively. Fibrinogen, a potential risk factor for CHD, was reduced by 26.2%. In contrast, the mean acute reduction of high density lipoprotein (HDL) was only 3.4%. During the course of the treatment, the time averaged levels of TC and LDL-C were reduced by approximately 39% and 50%, respectively, compared to baseline levels. The adverse events (AEs) were those generally associated with extracorporeal treatments. The most common AE was hypotension, with 69 episodes corresponding to 1% of all treatments reported in 44 of the 120 patients treated. All other kinds of AEs occurred in less than 0.2% of the treatments. The treatment with the Liposorber LA-15 system was overall well tolerated. It should be noted, however, that a more severe type of hypotensive reaction associated with flush, bradycardia, and dyspnea was reported in patients taking concomitant angiotensin converting enzyme (ACE) inhibitor medication. Except for such anaphylactoid-like reactions associated with the intake of ACE inhibitors, the Liposorber LA-15 system represents a safe and effective therapeutic option for patients suffering from severe hypercholesterolemia that could not be adequately controlled by diet and maximum drug therapy.

Successful treatment of homozygous familial hypercholesterolemia using cascade filtration plasmapheresis

“…In the presentstudy the mean decrease in IgG was 30.9% and was withinthe normal range for the patients’ age group. Mean decreasein IgG ranged from 27% to 32% in other studies [25,27]. Although acute mean reductions of 59.7% in fibrinogen,21.5% in serum protein, 14.7% in serum albumin, and14.2% in platelets were noted, we did not observe any infection,hemorrhagia, or edema in our patients.…”

Successful Treatment Of Homozygous Familial Hypercholesterolemia Using Cascade Filtration Plasmapheresis

“…In the present study the mean decrease in IgG was 30.9% and was within the normal range for the patients' age group. Mean decrease in IgG ranged from 27% to 32% in other studies [25,27]. Although acute mean reductions of 59.7% in fibrinogen, 21.5% in serum protein, 14.7% in serum albumin, and 14.2% in platelets were noted, we did not observe any infection, hemorrhagia, or edema in our patients.…”

Approach to Reduction of Blood Atherogenicity

“…It is known that lowering LDL including modified LDL in the blood of patients using drug therapy or extracorporeal LDL removal causes regression of atherosclerosis [10–12]. In the present work we have shown a significant impact of nonlipid factor(s) to blood atherogenicity.…”