B. Mazzarella

Treatment of symptomatic hyperLp(a)lipidemia with LDL-apheresis vs. usual care

BACKGROUND/AIMS To assess LDL-apheresis efficacy to lower Lp(a) and to compare the effects of Usual Medical Care (UMC) a 12-months study was carried out. The incidence of new coronary artery disease (CAD) events/need of revascularization, was also monitored. METHODS Twenty-one patients with hyperLp(a)lipidemia and angiographically documented CAD were randomly assigned to LDL-apheresis every week, or the UMC. RESULTS LDL-apheresis group, averaged an Lp(a) reduction of 57.8+/-9.5% vs. basal values (P<0.001). In the UMC group Lp(a) increased in 1 year to 14.7+/-36.5% (P=0.66). Stepwise multivariate regression analysis for predictors of Lp(a) including: type of treatment, smoking, hypertension, age, age at first cardiovascular event, initial Lp(a), LDL, and BMI values, was performed. Only the type of treatment was co-related (P<0.001): Lp(a) variation (beta)=0.863. The model has R2 adjusted relative risk of 0.725. CONCLUSION LDL-apheresis could be the first line treatment of isolated hyperLp(a)lipidemia when CAD is established. New CAD events/cardiac interventions were not observed.

Aorta and coronary angiographic follow-up of children with severe hypercholesterolemia treated with low-density lipoprotein apheresis

BACKGROUND: In this single‐center, nonrandomized, prospective study, 11 children with severe genetic hypercholesterolemia, without previous cardiovascular disease events, were treated with low‐density lipoprotein apheresis (LDLa).

Treatment of homozygous and double heterozygous familial hypercholesterolemic children with LDL-apheresis.

Within the framework of a seven-year clinical experience on treatment of severe hyperlipoproteinemia with/without associated coronary heart disease, with therapeutic plasmapheresis (APO B-100-containing lipoprotein-apheresis), we focused the present report on two young patients aged 7 and 11 years, respectively. The older patient is a boy treated since 1990 by plasma-exchange, cascade filtration-low density lipoprotein apheresis (LDL-apheresis), and dextrane sulphate-LDL apheresis. Over the treatment period the patient was submitted to three consecutive coronary angiographies. The second patient is a girl first submitted to a coronary angiography and then treated with dextrane sulphate-LDL apheresis. Up to now, a total of one-hundred therapeutic plasmaphereses have been performed. The interval of treatment was of fifteen days, and a volume of 2-3000 ml of plasma was processed at each session. The systems used were the following: DIDECO Vivacell BT 798-A, DIDECO Vivacell BT 798-A + BT 803, DIDECO BT 985 (Dideco, Mirandola, Italy), KANEKA MA-01 (Kanegafuchi, Osaka, Japan). Mean (SD) plasma apo B-100-containing major lipoprotein-LDL, Lp(a) - levels during treatment, are reported below: LDL-Apheresis mg/dl   LDL-Chol   Lp(a) before   479 (83)   58 (15) after   103 (67)   21 (14) The treatment was very well tolerated. Rare, moderate hypotensive events occurred. Nevertheless, all procedures were regularly completed. A mild hypochromic anemia, regressed using drug treatment, was observed in the boy. Along with the improvement of plasma atherogenic profile, a regression of skin xanthomas and unchanged favourable coronary angiograms, were obtained in the above mentioned patient.

Effects of Low-Dose Atorvastatin and Rosuvastatin on Plasma Lipid Profiles A Long-Term, Randomized, Open-Label Study in Patients with Primary Hypercholesterolemia

Background and objectiveDespite the favorable effects of reduction of low-density lipoprotein-cholesterol (LDL-C) levels in decreasing the risk of coronary heart disease, many patients treated with lipid-lowering HMG-CoA reductase inhibitors (statins) do not achieve goal LDL-C levels. This may be due to high doses of statins prescribed that could potentially induce adverse effects and compromise patient safety and compliance with considerable expense in the long-term. We compared the actions of rosuvastatin and atorvastatin, administered at the low dosages of 10 and 20 mg/day, respectively, in reducing plasma LDL-C levels and their effects on other components of the atherogenic lipid profile in patients with primary hypercholesterolemia.MethodsIn this randomized, parallel group, open-label clinical study, 106 patients with LDL-C >200 mg/dL were treated with rosuvastatin 10 mg/day (group A; n = 52), or atorvastatin 20 mg/day (group B; n = 54) for 48 weeks.ResultsAt 48 weeks, rosuvastatin 10 mg/day was associated with a significantly greater reduction in plasma LDL-C levels compared with atorvastatin 20 mg/day (−44.32% vs −30%; p < 0.005). Compared with atorvastatin, rosuvastatin also produced a greater reduction in plasma total cholesterol, triglycerides, and non-high-density lipoprotein-cholesterol (non-HDL-C) levels (p < 0.005). Plasma HDL-C levels were not affected significantly, independent of the drug used.ConclusionIn high-risk patients with primary hypercholesterolemia, rosuvastatin 10 mg/day was more efficacious than atorvastatin 20 mg/day in reducing plasma LDL-C levels, enabling goal LDL-C levels to be achieved and improving other lipid parameters. Both treatments were well tolerated over 48 weeks.

LDL Apheresis: A Novel Technique (LIPOCOLLECT 200)

Therapeutic means to lower Lp(a) are limited. The most effective method to reduce plasma Lp(a) concentration significantly is therapeutic apheresis, namely, low-density lipoprotein (LDL) lipoprotein(a) (Lp(a)) apheresis. A novel technique based on reusable LDL adsorber called Lipocollect 200 (Medicollect, Rimbach, Germany) allows the removal of both LDL and Lp(a) from plasma. Two male patients with hyperLp(a)lipoproteinemia and angiographically established progressive coronary heart disease, without rough elevation of LDL-cholesterol, who did not respond to diet and medication were submitted to 50 LDL Lp(a) aphereses with Lipocollect 200 LDL Lp(a)-adsorber at weekly and biweekly intervals. Total cholesterol and LDL cholesterol plasma levels fell significantly by 48.3% (+/-6.7) to 61.6% (+/-12.7) (first patient), and 42.5% (+/-6.3) to 60.6% (+/-14.3) (second patient), respectively (all differences: P < or = 0.001). High-density lipoprotein (HDL)-cholesterol concentration in plasma did not show statistically significant change. Plasma triglycerides were also significantly reduced by 43.6% (+/-24.4) (first patient) and 42.3% (+/-13) (second patient) (both differences: P < or = 0.001). Plasma Lp(a) showed a statistically significant percent reduction in plasma as expected: 64.7 +/- 9.5 (first patient), and 59.1 +/- 6.7 (second patient) (both differences: P < or = 0.001). Plasma fibrinogen concentration was decreased by 35.9% (+/-18.7) (P < or = 0.05) (first patient) and 41.8% (+/-11.5) (second patient) (P < or = 0.005). Considering the reduction rate between the first and the last procedures, we have compared the mean percent reduction of the first five treatments (from session #1 to #5) with the last five treatments (from session #21 to #25). We have observed an increasing reduction of all activity parameters on both patients apart from HDL-cholesterol (first patient) and triglyceride (second patient) that showed a decreasing reduction rate. Both patients followed the prescribed schedule and completed the study. Clinically, all sessions were well tolerated and undesired reactions were not reported. The Lipocollect 200 adsorber proved to have a good biocompatibility. In this study, the adsorber reusability for several sessions was confirmed.

Platelet Activation in Hypercholesterolemic Patients Submitted to Therapeutic Plasmapheresis. An Ultrastructural Study.

Therapeutic plasmapheresis has been recommended as the choice therapy in patients with familial hypercholesterolemia. Little is known about the effect of plasmapheresis on platelet behavior. By means of electron microscopy we have studied the platelet plasma membrane of 4 patients with familial hypercholesterolemia who were submitted to repeated plasmaphereses. After each procedure of plasmapheresis, at the 15th day, morphometrical studies revealed a statistically significant increase in the surface density of the Open Canalicular System, which is considered a marker of platelet activation. However, during 12 months of plasmapheresis, a significant mean decrease in the morphometric parameters was observed. On one hand, these results indicate the necessity to consider the blood hemocoagulatory state in the patient who has been submitted to the above mentioned treatment, since the variation of these parameters after the therapeutic procedure, in a short time, could be potentially harmful to the patient; on the other hand, these results indicate, for the first time, the ability of the procedure to improve platelet behavior after repeated treatments on long term basis.

A new treatment of refractory ascites: ascitoapheresis.

Ascites is a clinical complication of several diseases (cirrhosis, heart failure, malignant neoplasms, etc.). The clinical feature of ascites is a fluid storage in peritoneal space causing progressive impairment of hemodynamic and respiratory functions leading to a definite worsening of the patient’s quality of life. The established therapeutic approach to ascites is pharmacological [ 13 (diuretics: spironolactone and furosemide), surgical [ 11 (liver transplantation, Le Veen shunt), and para-surgical (paracentesis with infusion of human albumin [2] and the Rhodiascit system [3]). The aim of our work was to study a novel non-pharmacological approach to the removal of ascitic fluid, represented by double filtration ascitoapheresis [4,5]. So far only three patients (mean age 58 ? 24 years, two males and one female) suffering from posthepatitic and alcoholic cirrhosis have been enrolled, and a total of 11 procedures have been carried out. Ascitoapheresis was accomplished by areverse double-filtration technique. A first filter (Albusave BT 902, DIDECO, Mirandola, Italy) of diacetate of cellulose with a cut off of 350,000 daltons was used first to remove from the ascitic fluid: macromolecules, active factors of coagulation, and pyrogens. The filtered liquid was then passed over a ultrai3tration systemmade of polyacrylonitrile (Pan 150 Ashai, Tokyo, Japan) to remove water and small molecules. As a consequence of this treatment ascitic fluid was reduced in volume by 80-90% and from 70% to 80% of the albumin was recovered 141. The procedure can be carried out using a conventional cell separator for cascade filtration or a dedicated apparatus such as the Dideco BT 990 used in this study. In Table I the mean 2 SD values of principal variables that we monitored during the treatment are summarized. A 72.6% recovery of ascitic liquid albumin and 77.7% of ascitic liquid total protein was obtained. All of the procedures were completed: the patients’ clinical symptoms were improved, and the treatment was well tolerated. A transient mild fever with mild hypotension was seen after the treatment in one patient. The most interesting result of our preliminary study on “ascitoapheresis” was the very significant recovery of serum albumin and total protein, obtained in all cases (Table II).

Variables involved in the treatment of severe hyperlipoproteinemias by combined drug and LDL-apheresis treatment

During clinical trials devoted to attaining the best possible control of severe hypercholesterolemia, a combination of adequate drug therapy and LDL-apheresis (LDL/A), should be put into practice. With relation to stopping the progression and/or obtaining the regression of preexisting coronary atherosclerotic lesions, this combination is a very promising one. Results depend on the intensity and frequency of this combination treatment. A long-term treatment with LDL/A can also be carried out without serious side effects, providing the patient’s clinical status is satisfactory and his vascular accesses are well-represented.