Evidence for maximal treatment of atherosclerosis: drastic reduction of cholesterol and fibrinogen restores vascular homeostasis.

This article summarizes the clinical and biochemical evidence for maximal treatment of atherosclerosis by a simultaneous 60% to 70% reduction of plasma low-density lipoprotein cholesterol (LDL cholesterol), fibrinogen, and lipoprotein a concentrations with heparin-mediated extracorporeal LDL/fibrinogen precipitation (HELP) apheresis and statins. Apheresis has proven efficient and safe in the treatment of more than 1,000 patients since 1984 and has been applied in children and adults for the treatment of homozygous and heterozygous familial hypercholesterolemia, coronary artery disease, ischemic cardiomyopathy, generalized atherosclerosis, or transplant-associated arteriosclerosis after cardiac transplantation. Simultaneous removal of the main atherogenic plasma compounds has an immediate impact on myocardial and peripheral vasomotion by increasing myocardial blood flow, coronary flow reserve, cerebral CO2-reactivity, and muscle oxygen tension. Removal of fibrinogen and cholesterol reduces plasma viscosity by 20% and erythrocyte aggregation by 60% which gives rise to applying the HELP apheresis in various microcirculatory disorders. Pilot studies on acute retinal ischemia, critical limb ischemia, and sudden hearing loss confirm this observation.     

Efficacy of different low-density lipoprotein apheresis methods.

Low-density lipoprotein (LDL) apheresis is a treatment option in patients with coronary heart disease and drug resistant hypercholesterolemia. Various apheresis systems based on different elimination concepts are currently in use. We compared the efficacy of 4 different apheresis systems concerning the elimination of lipoproteins. The study included 7 patients treated by heparin extracorporeal LDL precipitation (HELP), 10 patients treated by immunoadsorption, 8 patients treated by dextran-sulfate adsorption, and 4 patients treated by cascade filtration. Ten subsequent aphereses were evaluated in patients undergoing regular apheresis for more than 6 months. Total cholesterol decreased by approximately 50% with all 4 systems. LDL cholesterol (LDL-C) (64-67%) and lipoprotein a [Lp(a)] (61-64%) were decreased more effectively by HELP, immunoadsorption, and dextran-sulfate apheresis than by the less specific cascade filtration system [LDL-C reduction 56%, Lp(a) reduction 53%]. Triglyceride concentrations were reduced by 40% (dextran-sulfate) to 49% (cascade filtration) and high-density lipoproteins (HDL) by 9% (dextran-sulfate) to 25% (cascade filtration). On the basis of plasma volume treated, HELP was the most efficient system (LDL-C reduction 25.0%/L plasma), followed by dextran-sulfate (21.0%/L plasma), cascade (19.4%/L plasma), and immunoadsorption (17.0%/L plasma). However, a maximal amount of 3 L plasma can be processed with HELP due to concomitant fibrinogen reduction while there is no such limitation with immunoadsorption. Therefore, the decision of which system should be used in a given patient must be individualized taking the pre-apheresis LDL concentration, concomitant pharmacotherapy, and fibrinogen concentration into account.     

Distinct effects of LDL apheresis by hemoperfusion (DALI) and heparin-induced extracorporeal precipitation (HELP) on leukocyte respiratory burst activity of patients with familial hypercholesterolemia

Hypercholesterolemia and oxidative stress are major risk factors in atherogenesis. In the last years, lipid apheresis has been established as an effective clinical therapy by lowering not only elevated plasma low-density lipoprotein (LDL) levels but also by reducing the incidence of cardiovascular events. The aim of the present study was to investigate peripheral leukocyte oxidant generation in patients with familial hypercholesterolemia (FH) undergoing regular LDL apheresis. The activity state of leukocytes was estimated prior to, immediately after, and 2 days after LDL apheresis carried out by two distinct techniques: hemoperfusion with the DALI system and heparin-induced extracorporeal LDL precipitation (HELP). Oxidant generating activity was measured by chemiluminescence (CL) in whole blood and isolated polymorphonuclear leukocytes (PMNL). The results of our study show increased baseline respiratory burst activities in FH patients as compared to healthy controls. Apheresis with the HELP system was followed by increases in leukocyte count, zymosan-induced whole blood CL, and plasma PMNL elastase levels. The DALI technique caused no changes in leukocyte count and elastase levels and decreased whole blood CL activity. Two days after lipid removal the observed changes returned to pre-apheresis levels. Leukocyte activity parameters before and after apheresis did not correlate with the corresponding plasma levels of triglycerides, total cholesterol, and LDL cholesterol, suggesting that different handling in the framework of both apheresis techniques rather than lipid profile changes during therapy accounted for leukocyte activity modulation.     

Treatment of hypercholesterolemia with heparin-induced extracorporeal low-density lipoprotein precipitation (HELP)

Familial hypercholesterolemia (FH) can cause early disability and death from premature atherosclerotic cardiovascular disease. Patients homozygous for the disease have very high plasma cholesterol, extensive xanthomatosis, and die from atherosclerosis in childhood or early adulthood. Past attempts to improve the prognosis included removal of cholesterol from the circulation by ileal bypass or biliary diversion. Neither treatment was successful. Direct removal by plasmapheresis of low-density lipoprotein (LDL), the primary carrier of cholesterol in plasma, was first performed on an FH homozygous patient in 1966. The treatment was well tolerated and led to rapid diminution of xanthomas. Other experimental treatments included selective LDL apheresis with monoclonal or polyclonal antibody affinity columns. A method for selective LDL apheresis was developed in 1983 by Armstrong, Seidel, and colleagues based on heparin precipitation of LDL at low pH. This method, called HELP, removes all apolipoprotein B-containing lipoproteins including LDL and lipoprotein (a), as well as some fibrinogen. LDL apheresis by HELP is well tolerated; the incidence of side effects is low, and the treatment has been associated with regression of cardiovascular disease. LDL apheresis, rather than liver transplantation, is the treatment of choice for patients with severe, life-threatening hypercholesterolemia which does not respond to diet and drug therapy. © 1996 Wiley-Liss, Inc.     

Effect of heparin-induced extracorporeal low-density lipoprotein precipitation (HELP) apheresis on hepatitis C plasma virus load.

Association of the hepatitis C virus (HCV) with apolipoprotein B containing lipoproteins has been suggested, and this led to the concept that the low-density lipoprotein (LDL) receptor may also serve as a candidate receptor for HCV uptake into the liver. We have investigated whether heparin-induced extracorporeal LDL precipitation (HELP) LDL apheresis treatment reduces HCV plasma load in 6 patients, all infected for more than 4 years with HCV and resistant against established anti-HCV therapy. HELP apheresis treatment caused an HCV-RNA decrease of 77.3% in mean. This decline was not correlated with LDL-cholesterol reduction. HCV-RNA was retained on the HELP filter as shown for 1 patient. The effect of RNA lowering was only transient due to the high turnover of HCV. However, HELP apheresis may open a window of opportunity for an immune-modulating and antiviral therapy in the interval between two apheresis procedures in patients with high virus load.     

Hyperlipoprotein(a)aemia in nephrotic syndrome

The nephrotic syndrome is frequently associated with hyperlipidaemia and hyperfibrinogenaemia, leading to an increased coronary and thrombotic risk, which may be enhanced by high lipoprotein (a) [Lp(a)] concentrations. We followed the quantitative and qualitative pattern of plasma lipoproteins over 18 months in a patient with nephrotic syndrome suffering from premature coronary artery disease and with elevated level of Lp(a) (470 mg dL⁻¹). Analysis of kinetic parameters after heparin-induced extracorporeal plasma apheresis revealed a reduced fractional catabolic rate for both low-density lipoprotein (LDL) and Lp(a). After improvement of the nephrotic syndrome, Lp(a) decreased to 169 mg dL⁻¹ and LDL concentrations were normalized. The decrease of Lp(a) was associated with an increase in plasma albumin concentrations. Analysis of apo(a) isoforms in the patient showed the presence of isoform S2 (alleles 10 and 19). Consequently, the authors' present strategy is to normalize the elevated Lp(a) and fibrinogen levels. For this purpose heparin-mediated extracorporeal LDL precipitation (HELP) apheresis is a promising regimen, helping to reduce the thrombotic risk and prevent coronary and graft atherosclerosis as well as the progression of glomerulosclerosis in our patient.     

Three low density lipoprotein apheresis techniques in treatment of patients with familial hypercholesterolemia: a long-term evaluation.

Low density lipoprotein (LDL) apheresis is a treatment option for patients with severe hypercholesterolemia not adequately responding to drug treatment who have developed coronary heart disease. We regularly treated 18 patients with immunoadsorption, 8 with heparin induced extracorporeal LDL precipitation (HELP) and 8 with dextran sulfate adsorption for a mean of 4.6 +/- 2.6 years. The effects on LDL cholesterol, high density lipoprotein (HDL) cholesterol, and lipoprotein (a) were comparable among all 3 techniques. Twelve patients were treated for longer than 5 years and 18 patients for longer than 3 years. The evaluation of coronary angiograms (23 patients) revealed a definite regression of coronary lesions in 3 patients; in all other patients, there was a halt in progression. Three patients suffered a sudden cardiac death and 1 patient a nonfatal myocardial infarction due to the occlusion of a coronary bypass. In 9 of 11 patients, no atherosclerotic lesions developed in the coronary bypasses. No severe side effect of either procedure was observed. In conclusion, aggressive lipid lowering by LDL apheresis can stabilize coronary atherosclerosis in most patients.     

Influence of single low-density lipoprotein apheresis on the adhesion molecules soluble vascular cellular adhesion molecule-1, soluble intercellular adhesion molecule-1, and P-selectin.

The aim of our study was to investigate the influence of single low-density lipoprotein apheresis (heparin extracorporeal low-density lipoprotein precipitation [HELP]procedure) on plasma concentrations of soluble adhesion molecules (sAMs) such as soluble vascular cellular adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), and P-selectin in patients with familial heterozygous hypercholesterolemia and documented coronary artery disease enrolled in a chronic weekly HELP apheresis. Before HELP apheresis, the mean plasma concentration of sVCAM-1 was 515 +/- 119 ng/ml, 204 +/- 58 ng/ml for sICAM-1, and 112 +/- 45 ng/ml for P-selectin. After single HELP apheresis, plasma concentrations of sAM declined significantly by 32 +/- 7%, 18 +/- 15%, and 33 +/- 25% for sVCAM- 1,sICAM-1 and P-selectin, respectively. After a 1 week interval, sAM concentrations rose to approximately the initial values. The concentrations of all sAMs studied were significantly lower in the plasma leaving than entering the filter. Due to filtration, the decline in plasma level of sVCAM-1, sICAM-1, and P-selectin was 62 +/- 19%, 51 +/- 39%, and 67 +/- 22%, respectively. In addition to lipid reduction, single HELP apheresis significantly lowers plasma concentrations of sVCAM-1, sICAM-1, and P-selectin.     

Low density lipoprotein hemoperfusion by direct adsorption of lipoproteins from whole blood (DALI apheresis): clinical experience from a single center.

The elimination of low density lipoprotein (LDL) and lipoprotein (a) (Lp[a]) by conventional LDL apheresis techniques can only be achieved in a cell-free medium and thus requires the initial separation of plasma from the blood cells. The present paper describes the first LDL hemoperfusion system which is able to adsorb LDL and Lp(a) directly from whole blood. This simplifies the procedure substantially. The adsorber consists of polyacrylate ligands linked to a modified polyacrylamide matrix. These negatively charged polyacrylate ligands interact with the positively charged apoprotein B moiety of LDL and Lp(a), which results in selective adsorption of these lipoproteins onto the column. Three hypercholesterolemic patients suffering from overt atherosclerotic complications were treated weekly by direct adsorption of lipoproteins (DALI) (n = 20 sessions each). All patients were on the highest tolerated dose of cholesterol synthesis enzyme (CSE) inhibitors. About 1.3 patient blood volumes were treated per session. The anticoagulation was performed with acid citrate dextrose (ACD-A). The following acute reductions were achieved: LDL: 66%; Lp(a): 63%; and triglycerides: 29%. High density lipoprotein (HDL) (-13%) and fibrinogen (-16%) were not substantially reduced. The sessions were essentially uneventful. Due to a low ACD-A infusion rate, no hypocalcemic episodes were registered. One patient on enalapril was treated without complications when this angiotensin converting enzyme (ACE) inhibitor was withdrawn 2 days prior to apheresis. In summary, in our hands, DALI apheresis proved to be a simple, safe, and efficient method of lipid apheresis in hypercholesterolemic patients refractory to conservative lipid lowering therapy.     

Coronary risk factor management for the prevention and treatment of graft vessel disease in heart transplant patients.

There is increasing evidence that atherogenic risk factors largely contribute to the pathogenesis of graft vessel disease (GVD) after heart transplantation. Initial endothelial damage of the transplant heart derives from reperfusion ischemia during operation, repeated infections, and rejection episodes. Immunosuppressive medication considerably increases low density lipoprotein (LDL) cholesterol, lipoprotein(a), and fibrinogen blood levels, which in turn further damage the endothelium of the graft coronaries. Probably, this interplay of immunological and atherogenic factors accounts for the rapid development of GVD and its poor prognosis. The rapidity of the disease process makes it necessary to eliminate important risk factors as early and as efficiently as possible. Therefore, we studied whether heart transplant patients could benefit from a combined treatment of statins and apheresis heparin extracorporeal LDL/fibrinogen precipitation (HELP), which has already been shown to be beneficial for the treatment of advanced coronary artery disease. Such a combined treatment allows simultaneous and drastic reduction of LDL, lipoprotein(a), and fibrinogen blood levels and significantly prevented GVD. Moreover, it did not affect the prevention of rejections and infections, respectively.     

Improved treatment of sudden hearing loss by specific fibrinogen aphaeresis

The etiology of sudden sensorineural hearing loss is still unclear and is thought to result from disturbances of microcirculation, infectious causes, or autoimmune disorders. So far standard therapy did not show clear improvement over spontaneous remission rate, which is assumed to be about 50% [Nakashima et al., Acta. Otolaryngol. Stockh. 514:14-16, 1994; Schuknecht and Donovan, Arch. Otorhinolaryngol. 243:1-15, 1986; Harris and Sharp, Laryngoscope 100:516-524, 1990; Mayot et al., Clin. Immunol. Immunopath. 68:41-45, 1993; Gussen, Ann. Otol. Rhinol. Laryngol. 85:94-100, 1976]. Elevated blood viscosity due to high fibrinogen levels is supposed to cause decreased cochlear blood flow and thus initiate sudden hearing loss. The specific lowering of fibrinogen immediately decreases plasma viscosity exactly to the desired extent and should lead to improved cochlear blood flow [Suckfüll et al., Acta. Otolaryngol 119:763-766, 1999; Suckfüll, Lancet 360:1811-1817, 2002; Walch et al., Laryngol. Rhino. Otol. 75:641-645, 1996; Suckfüll et al., Otol. Neurotol. 23:309-311, 2002]. In a prospective uncontrolled pilot study on 36 patients with unilateral sudden onset sensorineural hearing loss (SHL) we tried to establish that 1-3 specific fibrinogen aphaereses alone improve recovery of hearing and that it is possible to lower fibrinogen to the target of 80-100 mg/dl without important side effects. Pure tone audiometry was carried out immediately before and after each aphaeresis as well as at 2 and 4 weeks and 6 months after treatment. Sixteen patients recovered spontaneously before undergoing fibrinogen adsorption. All 20 aphaeresis patients improved during immunoadsorption; in 60% of patients auditory thresholds returned to normal after the first immunoadsorption and treatment could be discontinued, in another 20% of patients complete recovery was reached after 4 weeks. The mean plasma fibrinogen concentration of the 20 patients before the first aphaeresis session was 308.1 +/- 51.5 mg/dl. Immediately after the first treatment session, the fibrinogen concentration was lowered to 100.7 +/- 25.3 mg/dl (P < 0.001). The second and third sessions also showed highly significant reductions in plasma fibrinogen. No important side effects were seen.In conclusion, specific fibrinogen adsorption is a promising new treatment modality that should be tested in a prospective, randomized controlled trial in patients with sudden hearing loss.     

Clinical application and effectiveness of low-density lipoprotein apheresis in the treatment of coronary artery disease.

The Low-Density Lipoprotein Apheresis Coronary Atherosclerosis Prospective Study (L-CAPS) examined whether or not combined low-density lipoprotein (LDL) apheresis and drug therapy apheresis could induce the regression of coronary atherosclerotic lesions in patients with familial hypercholesterolemia. Twenty-eight patients treated with LDL apheresis and drugs and 11 patients treated with drugs alone underwent sequential coronary angiography 2.5 years apart. The frequency of cases with regression or no change was significantly higher for the apheresis group than for the control group (p = 0.004). The LDL apheresis Angioplasty Restenosis Trial (LART) investigated the hypothesis that high plasma lipoprotein (a) (Lp[a]) levels were associated with increased incidences of restenosis after coronary angioplasty. Two days before and 5 days after angioplasty, 66 patients underwent LDL apheresis. The restenosis rates were 21% in the 42 patients whose Lp(a) levels were reduced > or = 50% and 50% in the 24 patients whose Lp(a) levels were reduced < 50% (p < 0.05). LDL apheresis is effective in the prevention of the progression of coronary atherosclerosis. Its potential application in restenosis prevention should be further investigated.     

Low density lipoprotein apheresis by membrane differential filtration (cascade filtration).

Membrane differential filtration (MDF) is an apheresis technique with which atherogenic lipoproteins can be eliminated from plasma on the basis of particle size. In 52 patients (REMUKAST Study, 1,702 treatments), low density lipoprotein (LDL) cholesterol was decreased by 61%, high density lipoprotein (HDL) cholesterol by 42%, and fibrinogen by 54%. Our own results in 3 patients show decreases of 62%, 31%, and 59%, respectively; lipoprotein (a) (Lp[a]) was reduced by 58%. The elimination of atherogenic lipoproteins was accompanied by a loss of macromolecules (IgM: 55%, IgG: 27%, alpha 2-macroglobulin: 49%) resulting in improved hemorrheologic parameters. Although HDL is eliminated with each apheresis session, pretreatment concentrations of HDL cholesterol increased by 24% during regular apheresis for 1 year (26 patients, REMUKAST Study). However, preapheresis concentrations of other macroglobulins such as immunoglobulins remained decreased compared to concentrations obtained before the first apheresis session (IgM: 34%, IgG: 23%, and IgA: 16%). We conclude that MDF apheresis is an effective method to lower elevated concentrations of atherogenic lipoproteins. The concomitant loss of other macromolecules transiently improves hemorrheology but demands a close monitoring of immunoglobulin concentrations as a safety parameter.     

The role of low density lipoprotein apheresis in the treatment of familial hypercholesterolemia.

The chief indication for low density lipoprotein (LDL) apheresis is the treatment of homozygous familial hypercholesterolemia (FH), a potentially fatal condition that responds poorly to conventional therapy. Dextran sulfate/cellulose adsorption columns (Kaneka) and on-line heparin precipitation (HELP) are the most popular systems used in LDL apheresis. Weekly or biweekly procedures plus concomitant drug therapy enable LDL cholesterol to be maintained at 30-50% of its untreated level, with regression of xanthomas, arrest of progression of coronary atherosclerosis, and improved life expectancy. However, aortic stenosis may progress despite apheresis and necessitate valve replacement. Better control of hypercholesterolemia results from combining apheresis with a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, atorvastatin. LDL apheresis can also be useful in treating drug-resistant FH heterozygotes with coronary disease. However, the FH Regression Study showed no evidence that reduction by apheresis of both LDL and lipoprotein(a), was more advantageous than reduction by combination drug therapy of LDL alone.     

Consistent lowering of clotting factors for the treatment of acute cardiovascular syndromes and hypercoagulability: a different pathophysiological approach.

Hypercoagulability is a key contributor to acute cardiovascular syndromes and to various microcirculatory disorders. The use of heparin-mediated extracorporeal low-density lipoprotein/fibrinogen precipitation (HELP) apheresis makes a controlled, immediately effective reduction of clotting factors possible, and induces subsequent positive effects on plasma viscosity, erythrocyte aggregation, and microcirculation. Oxygen supply to an ischemic artery can thus be increased without hemodilution, qualifying the HELP system as a possible therapeutic tool in the treatment of acute cardiovascular syndromes and microcirculatory disorders.     

Current topics on low-density lipoprotein apheresis.

The prognosis of patients suffering from severe hyperlipidemia, sometimes combined with elevated lipoprotein (a) (Lp[a]) levels, and coronary heart disease (CHD) refractory to diet and lipid-lowering drugs is poor. For such patients, regular treatment with low-density lipoprotein (LDL) apheresis is the therapeutic option. Today, there are four different LDL-apheresis systems available: immunoadsorption, heparin-induced extracorporeal LDL/fibrinogen precipitation, dextran sulfate LDL-adsorption, and LDL-hemoperfusion. Despite substantial progress in diagnostics, drug therapy, and cardiosurgical procedures, atherosclerosis with myocardial infarction, stroke, and peripheral cellular disease still maintains its position at the top of morbidity and mortality statistics in industrialized nations. Established risk factors widely accepted are smoking, arterial hypertension, diabetes mellitus, and central obesity. Furthermore, there is a strong correlation between hyperlipidemia and atherosclerosis. Besides the elimination of other risk factors, in severe hyperlipidemia (HLP) therapeutic strategies should focus on a drastic reduction of serum lipoproteins. Despite maximum conventional therapy with a combination of different kinds of lipid-lowering drugs, however, sometimes the goal of therapy cannot be reached. Mostly, the prognosis of patients suffering from severe HLP, sometimes combined with elevated Lp(a) levels and CHD refractory to diet and lipid-lowering drugs is poor. Hence, in such patients, treatment with LDL-apheresis can be useful. Regarding the different LDL-apheresis systems used, there were no significant differences with respect to the clinical outcome or concerning total cholesterol, LDL, high-density lipoprotein, or triglyceride concentrations. With respect to elevated Lp(a) levels, however, the immunoadsorption method seems to be the most effective. The published data clearly demonstrate that treatment with LDL-apheresis in patients suffering from severe hyperlipidemia refractory to maximum conservative therapy is effective and safe in long-term application.     

Influence of atorvastatin versus simvastatin on fibrinogen and other hemorheological parameters in patients with severe hypercholesterolemia treated with regular low-density lipoprotein immunoadsorption apheresis.

Low-density lipoprotein (LDL) apheresis is a treatment option in patients with coronary artery disease and elevated LDL cholesterol concentrations if maximal drug therapy fails to achieve adequate LDL cholesterol reduction. This therapy is more effective when combined with strong lipid-lowering drugs, such as atorvastatin. However, conflicting data have been published concerning the effect of atorvastatin on fibrinogen concentration. Therefore, we investigated the effect of atorvastatin compared to simvastatin on fibrinogen concentration and other hemorheological parameters in patients treated by weekly LDL apheresis. Hemorheological parameters were, studied twice in 9 patients (4 female, 5 male, 54.0+/-8.9 years) with coronary artery disease treated by weekly LDL immunoadsorption, once during concomitant simvastatin therapy (40 mg daily) and once during atorvastatin therapy (40 mg daily). Fibrinogen concentration, plasma and blood viscosity at different shear rates, parameters of red cell aggregation at stasis and shear rate 3/s, and erythrocyte filterability were determined 7 days after the last LDL apheresis after each drug had been given for a minimum for 8 weeks. Fibrinogen concentration did not show any statistically significant difference during therapy with atorvastatin (3.09+/-0.36 g/L) compared to simvastatin (3.13+/-0.77 g/L). Plasma and blood viscosity as well as erythrocyte filterability were also unchanged. The increase in red cell aggregation at stasis during atorvastatin treatment (5.82+/-1.00 U versus 4.89+/-0.48 U during simvastatin; p < 0.05) was inversely correlated with a lower high-density liprotein (HDL) cholesterol concentration (1.17+/-0.21 mmol/L versus 1.31+/-0.30 mmol/L during simvastatin; p < 0.05). LDL cholesterol showed a strong trend to lower concentrations during atorvastatin (4.14+/-0.61 mmol/L versus 4.56+/-0.66 mmol/L during simvastatin; p = 0.07), despite a reduced plasma volume treated (3,547+/-1,239 ml during atorvastatin versus 3,888+/-1,206 mL during simvastatin; p < 0.05). In conclusion, fibrinogen concentration and other hemorheological parameters were unchanged during atorvastatin compared to simvastatin therapy with the exception of a higher red cell aggregation at stasis. Therefore, with respect to hemorheology, we conclude that atorvastatin should not be withheld from hypercholesterolemic patients regularly treated with LDL immunoadsorption.     

LDL apheresis in clinical practice: long-term treatment of severe hyperlipidemia.

Thirty patients (13 males, 17 females) suffering from familial hypercholesterolemia resistant to diet and lipid-lowering drugs were treated for 48.7 +/- 19.2 months (range, 2-87 months) with low density lipoprotein (LDL) apheresis. Three different systems (dextran sulfate adsorption for 27 of 30 [Kaneka, Liposorber, Japan], immunoadsorption system for 2 of 30 [Baxter, Therasorb, Germany], immunoadsorption system with special lipoprotein a [Lp(a)] columns for 1 of 30 patients [Lipopak, Pocard, Russia]) were applied. Before LDL apheresis 24 of 30 patients suffered from coronary heart disease (CHD) with angina symptoms. With LDL apheresis, reductions of 46% for total cholesterol, 49% for LDL, 30% for Lp(a), and 38% for triglycerides were reached. Severe side effects such as shock or allergic reactions were very rare (0.5%). In the course of treatment, an improvement in general well-being and increased performance were experienced in 27 of 30 patients. A 60 to 100% reduction of nitrate medication was observed in 17 of 24 patients. Regarding the different apheresis systems used, at the end of the trial there were no significant differences with respect to the clinical outcome experienced by the patients and concerning total cholesterol, LDL, high density lipoprotein, and triglyceride concentrations. But to reduce high Lp(a) levels, the immunoadsorption method with special Lp(a) columns seems to be the most effective (-57% versus 25% [Kaneka] and 23% [Baxter]). The present data clearly demonstrate that treatment with LDL apheresis of patients suffering from familial hypercholesterolemia, resistant to maximum conservative therapy, is very effective and safe, even in long-term application.     

Comparison of different LDL apheresis methods

This article presents the generally accepted indications for LDL apheresis treatment. The available LDL apheresis methods differ with respect to acute relative reductions of LDL cholesterol; mean values after the LDL apheresis treatments are not different. Serum triglycerides, HDL-cholesterol, and lipoprotein(a) are also acutely reduced. Available LDL apheresis methods differ with respect to their impact on the coagulation system, on C-reactive protein and on leukocyte count. Cardiovascular events are clearly reduced by the LDL apheresis methods. There is an urgent need to prospectively compare the different LDL apheresis methods taking into account hard end points. The lower target values for LDL cholesterol suggested by international guidelines for high-risk patients will certainly require a more widespread use of LDL apheresis.     

Comparison of different LDL apheresis methods

This article presents the generally accepted indications for LDL apheresis treatment. The available LDL apheresis methods differ with respect to acute relative reductions of LDL cholesterol; mean values after the LDL apheresis treatments are not different. Serum triglycerides, HDL-cholesterol, and lipoprotein(a) are also acutely reduced. Available LDL apheresis methods differ with respect to their impact on the coagulation system, on C-reactive protein and on leukocyte count. Cardiovascular events are clearly reduced by the LDL apheresis methods. There is an urgent need to prospectively compare the different LDL apheresis methods taking into account hard end points. The lower target values for LDL cholesterol suggested by international guidelines for high-risk patients will certainly require a more widespread use of LDL apheresis.