Extracorporeal Removal of Lipids by Dextran Sulfate Cellulose Adsorption

Abstract: Extracorporeal removal of low–density lipoprotein (LDL) cholesterol by dextran sulfate adsorption is indicated in patients with diet and drug resistant hypercholesterolemia to prevent or to regress coronary heart disease. Plasma separation is the first step in the process, followed by adsorption of LDL cholesterol and lipoprotein (a) (Lp[aJ) to negatively charged dextran sulfate co–valently bound to cellulose beads. The reduction per treatment in LDL cholesterol is 65–75% and in Lp(a) 40–60%. In most patients one treatment per week is sufficient to reduce mean LDL to 100–150 mg/dl. Minor side effects occur in 2–6% of treatments. Major side effects are rare. In uncontrolled studies long–term treatment was associated with inhibition of progression and induction of regression of coronary artery disease. LDL apheresis by dextran sulfate may increase blood perfusion of some tissues, and preliminary results indicate a beneficial effect on therapy resistant nephrotic syndrome with hypercholesterolemia.     

Heparin–Induced Extracorporeal Low–Density Lipoprotein Precipitation and Low–Density Lipoprotein Chemoadsorption onto Dextran Sulfate: A Comparison

Abstract: Both heparin–induced extracorporeal low–density lipoprotein precipitation (HELP) and dextran sulfate (DS) apheresis are potent tools for acute and long–term risk factor reduction in the secondary prevention treatment of coronary patients suffering from recalcitrant hypercholesterolemia. They combine high efficacy and selectivity of risk factor removal. Whereas LDL cholesterol and lipoprotein (a) adsorption onto DS offers the advantage of an unlimited treatable plasma volume and somewhat easier handling, HELP reduces fibrinogen more effectively and does not interfere with angiotension converting enzyme (ACE) inhibitors. Both systems can improve blood rheology and induce regression or stabilize coronary lesions. In an uncontrolled trial, HELP reduced the incidence of myocardial infarction. To date, no controlled prospective trials have been performed comparing the two systems with respect to their long–term risk factor reduction and their effect on coronary lesions, morbidity, and mortality.     

Treatment of Severe Hyperlipidemia: Six Years' Experience with Low–Density Lipoprotein Apheresis

Abstract: In total, 30 patients suffering from familial hypercholesterolemia, resistant to diet and lipid–lowering drugs, were treated for up to 6 years (3.6 ± 1.6; range, 0.2–6.8 years) with low–density lipoprotein (LDL) apheresis. Three different systems were used; the dextran sulfate adsorption system (Kaneka) for 27 of 30 patients, the immunoadsorption system from Baxter for 2 of 30 patients, and the immunoadsorption system with special li–poprotein(a) (Lp[a]) columns from Lipopak for one patient. Prior to the LDL apheresis, 23 of 30 patients suffered from coronary heart disease. Twenty of 23 patients suffered intermittently from symptoms of angina, excertional dyspnea, and claudication. With LDL apheresis, reductions of 47% for total cholesterol, 49% for LDL, 26% for Lp(a), and 40% for triglycerides were reached. Severe side effects such as shock or allergic reactions were very rare (0.55%). In the course of treatment with LDL apheresis, an improvement in general well–being and increased performance were experienced in 27 of 30 patients. A reduction of nitrate medication between 60 and 100% was observed in 17 of 23 patients. The present data clearly demonstrate that treatment with LDL apheresis in patients suffering from severe familial hyperlipidemia, resistant to maximum conservative therapy, is very effective and safe even over long periods of time.     

LDL Apheresis in a Homozygous Familial Hypercholesterolemic Child Aged 4.5

Abstract: Preliminary experience with the efficacy and safety of dextran sulfate cellulose low-density lipoprotein (LDL) apheresis for the treatment of a 4.5-year-old girl with homozygous familial hypercholesterolemia and coronary artery disease is reported. The decrease of the most atherogenic apolipoprotein B-containing lipoproteins, low-density lipoprotein (LDL) and lipoprotein(a) (Lp [a]), were in the ranges of 63.1–68.7%, and 52.5–58.6%, respectively. The child tolerated LDL apheresis without any clinically significant complications. Therefore, she was submitted to a long-term program of treatment at intervals of 15 days. The experience suggests the possibility of an early beginning of extracorporeal treatment with LDL apheresis in children severely affected by homozygous or double heterozygous familial hypercholesterolemia.     

Lipid Apheresis: From a Heroic Treatment to Routine Clinical Practice

Abstract: Lipid apheresis has developed from a heroic treatment into a routine clinical therapy and currently is the major indication for performing extracorporeal plasma therapy. Whereas it was once reserved for patients with homozygous familial hypercholesterolemia, today it has a place in the secondary prevention of severe coronary heart disease when low-density lipoprotein (LDL)-cholesterol levels exceed 150 mg/dl, despite conservative treatment, in any type of primary hypercholesterolemia. Unselective plasma exchange has been replaced by a variety of selective procedures. The efficacy of the treatment can be maximized by combining LDL apheresis with the use of cholesterol synthesis enzyme inhibitors. Clinical studies have shown that drastic cholesterol reduction can result in regression of coronary atherosclerosis as well as in reduced cardiac morbidity and mortality. Technical progress comprises improved selectivity, online regeneration of adsorbers, and LDL adsorption from whole blood. Recently, a new LDL hemoper-fusion procedure was successfully tested in a clinical pilot study; blood is passed directly over a lipid sorbent without prior plasma separation. If this system is demonstrated to be safe and effective in clinical Phase III trials, a further qualitative step in the rapid development of LDL apheresis will have been made.     

State of the Art of Lipid Apheresis

Abstract: Currently, 5 different lipid apheresis procedures are available for routine clinical treatment of hy–percholesterolemic patients. Unselective plasma exchange is a technically simple extracorporeal circuit, but albumin substitution fluid must be used and there is no high–density lipoprotein (HDL) recovery. Semiselective double filtration with improved size selectivity because of a small–pore secondary filter combines good elimination of low–density lipoprotein (LDL), lipoprotein (a) (Lp[a]), and fibrinogen with adequate HDL recovery; modifications such as thermofiltration, predilution/backflush, or pulsatile flow have been proposed for the improvement of this system. Three highly selective procedures are basedon immunologic or electrostatic interactions: immunoad–sorption using anti–low–density lipoprotein (LDL) antibodies, chemoadsorption onto dextran sulfate, and hep–arin–induced LDL precipitation (HELP) apheresis. The features of each system are discussed critically. Lastly, two new developments, Lp(a) immunoadsorption and LDL hemoperfusion using a polyacrylate LDL adsorber compatible with whole blood, are described     

HELP Apheresis in the Treatment of Sepsis

Heparin induced extracorporeal lipoprotein fibrinogen precipitation (HELP) is an established procedure for removal of low-density lipoprotein (LDL) cholesterol, lipoprotein (a), and fibrinogen in patients with severe hypercholesterolemia. In vitro studies revealed that HELP also removes endotoxin, tumor necrosis factor α (TNF-α) and C-reactive protein (CRP). With the intention to treat, we applied this procedure to 4 patients with severe gram-negative sepsis with highly elevated endotoxin blood levels. Nine treatments were performed, 6 using the standard HELP precipitating buffer and 3 without addition of heparin to the precipitating buffer. Heparin was omitted from the precipitating buffer to avoid fibrinogen depletion in patients at risk (low fibrinogen, postoperative). The average processed plasma volume was 3,386 ml in the standard and 2,963 ml in the modified treatment. Mean reductions (%) in plasma solute concentrations were (standard/modified procedure) as follows: endotoxin, 50/57; TNF-α, 25/5; CRP, 49/55; fibrinogen, 49/6; total cholesterol, 38/5; and apolipoprotein B (Apo B), 41/2. Both treatment modalities were equally effective in removing endotoxin and CRP. With the modified precipitation buffer, fibrinogen was not removed. To further simplify the extracorporeal treatment, we have designed a closed-loop circuit with 2 adsorbers in series, one for removal of TNF-α (dextran sulfate modified cellulose) and the other for removal of endotoxin (DEAE-cellulose). In vitro evaluation confirmed very efficient endotoxin and TNF-α removal from plasma. This system is very simple, operates at physiological pH, and uses adsorbers already in clinical use for other purposes.     

Extracorporeal treatment of hypercholesterolaemia

Extracorporeal removal of LDL cholesterol (LDL apheresis) hasbeen carried out in patients with diet- and drug-resistant hypercholesterolaemiato prevent or to reduce coronary heart disease. Plasma separationis the first step in all five LDL-apheresis methods presentlyavailable. Plain plasma exchange and double-membrane filtrationare unselective and remove HDL cholesterol and plasma proteins.Adsorption of LDL to dextran sulphate, to LDL antibodies, orprecipitation of LDL by heparin at low pH are more selective.With all methods LDL cholesterol reduction per treatment is60–70%. In most patients one treatment per week is sufficientto reduce mean LDL to 100–150 mg/dl. Minor side-effectsoccur in 10±5% of treatments. Major side-effects arerare. Long-term LDL apheresis increased survival in patientswith homozygous familial hypercholesterolaemia. In heterozygousfamilial hypercholesterolaemia controlled studies regardingsurvival are not available. Uncontrolled trials indicate regressionof coronary artery disease in heterozygotes with drug- and diet-resistantLDL cholesterol > 200 mg/dl. Hence, LDL apheresis is indicatedin all patients with homozygous familial hypercholesterolaemia.LDL apheresis in heterozygous familial hypercholesterolaemiashould be restricted to patients with diet- and drug-resistantLDL cholesterol >200 mg/dl with coronary heart disease and/orother atherosclerotic vascular lesion.     

Efficacy and safety of a new whole-blood low-density lipoprotein apheresis system (Liposorber D) in severe hypercholesterolemia

Low-density lipoprotein (LDL) apheresis is an extracorporeal modality to lower LDL cholesterol. While most of the devices eliminate LDL particles from plasma, a recently introduced whole-blood perfusion column (DALI) adsorbs lipoproteins directly from whole blood. We investigated the efficacy and safety of a new whole-blood LDL apheresis system (Liposorber D) in 10 patients with severe hypercholesterolemia in a multicenter trial. In 93 LDL aphereses, the mean reduction in LDL cholesterol and lipoprotein(a) was 62.2 +/- 11.5% and 55.6 +/- 16.9%, respectively (P < 0.01). If hemodilution during apheresis was considered, the reductions were 58.0 +/- 10.9 and 55.3 +/- 10.9%, respectively (P < 0.01), while high-density lipoprotein (HDL) cholesterol did not change significantly. Three mild episodes of hypocalcemia and two mild episodes of arterial hypotension were observed; however, LDL apheresis could be continued in each case. In conclusion, the new whole-blood LDL apheresis with Liposorber D is a safe, simple, and useful modality to reduce LDL cholesterol and lipoprotein(a) in cardiovascular high-risk patients.     

Serum Amyloid A and P Protein Levels are Lowered by Dextran Sulfate Cellulose Low-Density Lipoprotein Apheresis

The present study describes the short-term effect of dextran sulfate cellulose (DSC) low-density lipoprotein (LDL) apheresis using a plasma separator equipped with a polysulfone (PS) membrane filter (PS/DSC-LDL apheresis) on the serum amyloid A (SAA) and P (SAP) protein levels during treatment in a patient with familial hypercholesterolemia (type IIa, heterozygote). PS/DSC-LDL apheresis markedly lowered both the SAA (reduction percentage, 84.1 ± 8.2%) and SAP (91.4 ± 5%) levels, which returned to their respective initial levels within 4 days. Experimentally, the levels of both proteins also decreased on passage through the DSC minicolumn without a PS membrane, indicating that the DSC resin had an affinity to both proteins. These results suggest that PS/DSC-LDL apheresis may be advantageous for amyloid protein accumulating disorders, including amyloidosis and atherosclerosis.     

Low–Density Lipoprotein Adsorption for Arteriosclerotic Patients

Abstract: A wide variety of treatments is now available for arteriosclerosis obliterans (ASO) patients, not very successful in some cases. Low—density lipoprotein (LDL) apheresis using an extracorporeal adsorption column containing dextran sulfate cellulose beads was applied to control lipid levels intensively in ASO patients with accompanying drug—resistant hyperlipidemia. A series of the apheresis procedures had a remarkable impact on clinical symptoms and physiological findings with improvement in intermittent claudication observed in more than 80% of the patients. Improvements in plethysmogram and thermogram readings suggested an increased circulation in lower extremities in more than 80% of patients. In addition, the treatment improved blood rheology, as evidenced by a reduction in blood viscosity. In a follow—up study made by sending a questionnaire to previously treated patients, it was revealed that improvements in clinical symptoms were well maintained even after cessation of the treatment. In conclusion, LDL apheresis proved to be a useful therapeutic tool in ASO patients having elevated lipid levels     

Low–Density Lipoprotein Apheresis Versus Lipid Lowering Drugs in the Treatment of Severe Hypercholesterolemia: Four Years' Experience

Abstract: Elevated lipoprotein concentrations seem to be linked strongly in a dose dependent manner to an increased incidence of atherosclerosis. A total of 47 patients suffering from severe hyperlipidemia were matched to treatment with LDL apheresis (Baxter, Kaneka, Li–popak; 24 patients, aged 50.2 ±11.5 years), diet, and/or lipid–lowering drugs or with diet and lipid–lowering drugs only (23 patients, aged 48.8 ±11.8 years). After treatment periods of 49.8 ±13.4 months (apheresis group, 2,396 treatment sessions) and 38.6 ± 15.1 months (drug group), the ensuing results revealed significant differences (p <0.0001): –47.3% versus –12.1% for total cholesterol, –46.9% versus –21.8% for LDL, +8.4% versus +0.9% for HDL, –52.0% versus – 13.1% for the LDL/HDL ratio, –36.4% versus –16.2% for triglycerides, and –25.9% versus + 1.5% for lipoprotein (a). In the apheresis group, one patient died of myocardial infarction; in the drug group, there was one nonfatal myocardial infarction and the manifestation of coronary heart disease in 3 cases. There were no severe side effects in either group. All patients in the apheresis group responded to therapy. The present trial suggests that a continuing reduction in serum lipid concentrations may lower, in a dose dependent manner, the risk for development and progression of coronary heart disease. Regarding clinical and laboratory results, LDL apheresis seems to be safe, effective therapy for treatment of severe hyperlipidemia.     

Low–Density Lipoprotein Apheresis in the Treatment of Two Patients with Coronary Heart Disease and Extremely Elevated Lipoprotein (a) Levels

Abstract: Hyperlipidemia and elevated lipoprotein (a) (Lp[a]) levels have been linked to the development and progression of premature atherosclerosis. Our study concerned 2 white male patients (aged 36 and 42 years) with heterozygous familial hypercholesterolemia and extremely elevated Lp(a) concentrations that were resistant to diet regimens and lipid–lowering drugs. The patients were treated with low–density lipoprotein (LDL) apheresis for 59 months (Liposorber system, Kaneka, Japan) and 19 months (immunoadsorption system, special Lp(a) columns; Lipopak; Pocard, Russia), respectively. The concentration of Lp(a) decreased on average by 50%, total cholesterol by 27%, LDL cholesterol by 41%, triglycerides by 43%, and fibrinogen by 16%. High–density lipoprotein (HDL) cholesterol increased by approximately 4%. Before treatment with LDL apheresis, each patient had suffered 3 myocardial infarctions, and had had 4 and 6 coronary angiographies with 2 and 4 percutaneous transluminal angioplasties (PTCAs), respectively. Since treatment with LDL apheresis, no myocardial infarctions or cardiac complaints were observed. In the course of treatment, both patients reported an increased performance. Available data suggest that LDL apheresis may be effective in the treatment of patients, the only risk factor for premature atherosclerosis being extremely elevated Lp(a) concentrations.     

Effects of HMG-CoA reductase inhibitors in hypercholesterolemic patients on hemodialysis

The efficacy of lovastatin and simvastatin, competitive inhibitors of 3-hydroxy-3-methyl glutaryl coenzyme A reductase, was investigated in 40 hemodialysis (HD) patients displaying hypercholesterolemia and moderate hypertriglyceridemia (selection of 40 patients required screening of 700 hemodialysis patients). After a four-week placebo period, lovastatin or simvastatin was administered to two groups of 20 patients in increasing doses over a period of three months. Thirty-six patients completed the study. Lovastatin (1st month 20 mg; 2nd and 3rd months 40 mg day-1) and simvastatin (1st month 10 mg, 2nd month 20 mg and 3rd month 40 mg day-1) reduced total serum cholesterol from 280.3 +/- 9.4 to 213.0 +/- 6.7 (-24%) and 295.0 +/- 12.2 to 202.3 +/- 8.9 mg/dl (-31.4%), LDL cholesterol from 161.9 +/- 10.7 to 112.1 +/- 7.9 (-30.8%) and 181.8 +/- 14.7 to 107.4 +/- 8.1 mg/dl (-40.9%), as well as apolipoprotein B (apo B) from 116.0 +/- 6.6 to 83.3 +/- 3.7 (-28.2%) and 134.4 +/- 8.2 to 84.1 +/- 5.3 mg/dl (-37.4%), respectively. Furthermore, the ratio of LDL apo B/LDL cholesterol increased significantly (0.63 +/- 0.02 vs. 0.71 +/- 0.05 and 0.63 +/- 0.02 vs. 0.66 +/- 0.02, respectively). Another remarkable effect was the reduction of cholesterol concentration in VLDL (72.4 +/- 8.9 vs. 47.3 +/- 6.8 [lovastatin] and 78.3 +/- 11.1 vs. 50.7 +/- 8.8 mg/dl [simvastatin], respectively). Therefore, the ratio of triglycerides/cholesterol in VLDL increased (3.2 +/- 0.2 vs. 3.8 +/- 0.3 and 3.2 +/- 0.2 vs. 4.0 +/- 0.2, respectively), indicating VLDL formation poor in cholesterol and rich in triglycerides.(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-term efficiency, biocompatibility, and clinical safety of combined simultaneous LDL-apheresis and haemodialysis in patients with hypercholesterolaemia and end-stage renal failure

Three hypercholesterolaemic patients on maintenance haemodialysiswith angiographically proven coronary artery disease were treatedin a once-a-week schedule by combined, synchronous lipid apheresis(using heparin-induced extracorporeal LDL precipitation) andhaemodialysis (HELP/HD) for 65–104 weeks. Clinical side-effectswere few and mostly related to high ultrafiltration rates inpatients with low compliance regarding interdialytic fluid restriction.Biocompatibility of the procedure was shown to be good and bloodcell losses, leukocyte (elastase release) and thrombocyte (ß-thromboglobulinextrusion) as well as complement (C3a formation) activationwere minimal. Interestingly, most of the C3a generated in theextracorporeal HELP circuit was immediately removed again inthe precipitate filter. In the pseudo-steady-state after 3 monthsof regular therapy, acute haematocrit-corrected reduction ofplasma components after the session compared to pre values wereabout 55% for the risk factors LDL cholesterol (LDL-C), lipoprotein(a)(Lp(a)), and fibrinogen (FIB) with good recovery of HDL-C andother proteins. Urea, creatinine, and phosphate eliminationwas similar to normal haemodialysis. Mean interapheresis values of risk factors after one (n=2) andtwo (n=1) years of treatment were crucially dependent upon ultrafiltration(UF); thus, in two patients with high UF LDL-C concentrationsamounting to 185 and 220mg/dl at baseline and were reduced toabout 135mg/dl LDL-C, while in the patient with low UF the reductionwas from 231 mg/dl to 80 mg/dl. The atherogenic index (LDL-C/HDL-C)was reduced from 6.4 and 5.1 to about 4.3 in patients with highUF, from 6.1 to 3.3 in the patient with low UF. Fibrinogen andLp(a) were normalized in all patients. In summary, the combined HELP/HD treatment in hypercholesterolaemicdialysis patients proved to be a safe, effective, and selectiveprocedure for lipoprotein and fibrinogen normalization withexcellent biocompatibility and good clinical patient tolerance,providing a tool ready for future atherosclerosis regressionstudies in ESRD patients.     

Treatment of Homozygous Familial Hypercholesterolemia with Low Density Lipoprotein Apheresis: A 4 Year Follow-Up Study

Abstract: Hypercholesterolemia and elevated lipoprotein (a) (Lp[a]) levels are considered to be risk factors for the development and progression of premature atherosclerosis. The purpose of our report is to describe the effects of low density lipoprotein (LDL) apheresis (Liposorber system, Kanegafuchi Chemical Industrial Company LTD, Osaka, Japan) on serum lipoprotein concentrations and the clinical status in 2 male patients with homozygous familial hypercholesterolemia. Compared with pretreatment values, the posttreatment concentrations of total cholesterol, LDL cholesterol, and Lp(a) were significantly reduced by 50–60% (p < 0.0001). The concentration of high density lipoprotein (HDL) cholesterol was slightly affected. After one treatment session, LDL cholesterol and Lp(a) were decreased on average by 65% and then increased to reach about 70–75% of the pretreatment values before the next session. Prior to the treatment with LDL apheresis, each patient had suffered one myocardial infarction and had had 2 coronary angiographies. After treatment with LDL apheresis, neither cardiac complaints nor myocardial infarction were observed. The xanthomas were much decreased during the treatment or disappeared. We conclude that LDL apheresis can be continued safely and without major technical problems for several years. Apheresis effectively lowers the serum levels of total and LDL cholesterol. Furthermore, it reduces Lp(a), which is not influenced by lipid-lowering drugs. The reduction of LDL cholesterol and Lp(a) may delay the progression of the atherosclerotic process, thereby helping to reduce the risk of new episodes of coronary heart disease and thus extending the life expectancy in these patients.     

Contact activation in low-density lipoprotein apheresis systems

BACKGROUND: Anaphylactoid reactions due to contact activation have been observed in patients on ACE inhibitor therapy and hemodialysis with negatively charged dialysis membranes. Negatively charged surfaces are functional constituents of different LDL apheresis systems. Therefore, contact activation was investigated during LDL apheresis with three different systems: (i) heparin-induced extracorporeal LDL precipitation (HELP); (ii) dextran sulfate cellulose (DSC) columns; and (iii) modified polyacrylate gels (DALI) in a clinical setting. METHODS: 24 prevalent patients on regular LDL apheresis treatment were included in the study. Bradykinin, prekallikrein, and HMW kininogen were measured during a single LDL apheresis at different sites of the systems. RESULTS: LDL apheresis with DSC and DALI was associated with an extreme release of bradykinin after the passage of plasma or blood through the LDL adsorbers as well as with a decrease of prekallikrein and HMW kininogen during the course of the treatment. Bradykinin release exceeded the degradation capacity of the kininase II, since markedly elevated bradykinin concentrations were observed in the arterial line of the extracorporeal circuits of both systems. This was not associated with anaphylactoid reactions. In contrast to the treatments with DSC and DALI, the HELP system did not lead to any activation of the kallikrein-kinin system. CONCLUSION: From our data we conclude that angiotensin converting enzyme (ACE) inhibitors are contraindicated in patients on LDL apheresis with the DSC and the DALI system. Because the HELP system does not activate the kallikrein-kinin system, patients who need ACE inhibitors are predisposed for this LDL apheresis procedure.     

Effect of simvastatin on qualitative and quantitative changes of lipoprotein metabolism in CAPD patients.

The efficacy of simvastatin, a competitive inhibitor of 3-hydroxy-3-methyl glutaryl coenzyme A reductase, was investigated in 12 patients treated with continuous ambulatory peritoneal dialysis (CAPD), displaying hypercholesterolemia and moderate hypertriglyceridemia. After a 4-week placebo period, simvastatin was administered in increasing doses over a period of 3 months (1st month 10 mg; 2nd month 20 mg and 3rd month 40 mg day-1). Simvastatin reduced total serum cholesterol (300.0 +/- 15.5 vs. 193.0 +/- 8.0; -35%), LDL cholesterol (203.8 +/- 13.0 vs. 104.7 +/- 6.0; -48.0%) as well as apolipoprotein B (132.3 +/- 6.6 vs. 77.8 +/- 2.7 mg/dl; -40%). Furthermore, the ratio of LDL apo B/LDL cholesterol increased significantly (0.55 +/- 0.016 vs. 0.64 +/- 0.027). Another remarkable effect was the reduction of cholesterol concentration in VLDL (47.8 +/- 5.6 vs. 30.4 +/- 5.2; -35%). Therefore, the ratio of triglycerides/cholesterol in VLDL increased (3.57 +/- 0.3 vs. 4.28 +/- 0.29), indicating VLDL formation poor in cholesterol and rich in triglycerides. However, HDL cholesterol increased significantly from 48.6 +/- 4.4 to 57.9 +/- 5.3 mg/dl (23%). Lipoprotein(a) levels were increased as compared to controls (420 +/- 73 vs. 145 +/- 26 U/l), but were not influenced significantly by simvastatin treatment (539 +/- 99 U/l, 3rd month). No evidence for notable clinical side effects and laboratory abnormalities were reported. Measurement of simvastatin plasma levels 12 h after drug administration (single dose 40 mg) showed no detectable plasma values. At present, it appears that CAPD patients with high serum cholesterol are good candidates for the treatment with HMG-CoA reductase inhibitors.     

Different Apheresis Methods in the Treatment of Hypercholesterolemia in Primary Biliary Cirrhosis: A Case Report

Abstract: The two different modes of low–density lipoprotein (LDL) apheresis, cascade filtration (CF) and dextransulfate cellulose (DSC) adsorption, were compared for efficiency of cholesterol removal in a patient with severe hypercholesterolemia due to primary biliary cirrhosis (PBC). Decrement in the total cholesterol level by the DSC method was less than that by the CF method. Apolipoprotein B was decreased to almost null by both modules whereas the decrease in albumin was much greater in the second filter of the CF method than in the DSC column. Lipoprotein X which constituted the major portion of serum cholesterol in PBC became negative by passing plasma through the second filter. The CF method was preferred to the DSC method for removal of lipoprotein X, but albumin substitution was mandatory to prevent the decrease of serum albumin in the CF method.     

Clinical evaluation of rosuvastatin in heart transplant patients with hypercholesterolemia and therapeutic failure of other statin regimens: short‐term and long‐term efficacy and safety results

We conducted an observational study of 30 heart transplant recipients with serum low‐density lipoprotein cholesterol (LDL‐c) >100 mg/dl despite previous statin therapy, who were treated with rosuvastatin 10 mg daily (5 mg in case of renal dysfunction). Serum lipids, creatine phosphokinase (CPK), bilirubin, and hepatic enzymes were prospectively measured 2, 4, and 12 weeks after the initiation of the drug. Clinical outcomes of patients who continued on long‐term rosuvastatin therapy beyond this 12‐week period were reviewed in February 2015. Over the 12‐week period following rosuvastatin initiation, serum levels of total cholesterol (TC) and LDL‐c and the ratio TC/high‐density lipoprotein cholesterol (HDL‐c) decreased steadily (P < 0.001). Average absolute reductions of these three parameters were –48.7 mg/dl, –46.6 mg/dl, and –0.9, respectively. Seventeen (57%) achieved a serum LDL‐c < 100 mg/dl. No significant changes from baseline were observed in serum levels of triglycerides, HDL‐c, hepatic enzymes, bilirubin, or CPK. Twenty‐seven (90%) patients continued on long‐term therapy with rosuvastatin over a median period of 3.6 years, with no further significant variation in lipid profile. The drug was suspended due to liver toxicity in 1 (3.3%) patient and due to muscle toxicity in 2 (6.7%) patients. All adverse reactions resolved rapidly after rosuvastatin withdrawal. Our study supports rosuvastatin as a reasonable alternative for heart transplant recipients with hypercholesterolemia and therapeutic failure of other statin regimens.