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The lower the better: Target values after LDL-Apheresis and semi-selective LDL-elimination therapies
Transfusion and Apheresis Science 48 (2013) 127
Contents lists available at SciVerse ScienceDirect
Transfusion and Apheresis Science journal homepage: www.elsevier.com/locate/transci
The lower the better: Target values after LDL-Apheresis and semi-selective LDL-elimination therapies Helmut Borberg German Haemapheresis Centre, Cologne, Germany
LDL-Apheresis was developed in Cologne and introduced into the clinical routine in 1980. The clinical value was supposed to be based on a controlled clinical trial (Statin vs. LDL-Apheresis vs. a combination of both) however instead the German Federal Ministry of Health granted an open multicentre trial at five German universities demonstrating that lowering of the total cholesterol to a value of 100–150 mg/dl post-treatment over a period of 3 years lead to a prevention of progression. Nevertheless, with a subsequent trial on a limited group of patients treated with LDL-Apheresis and Statins, we could demonstrate that the post-treatment synthesis rate could be lowered, if the medication was tolerated. As the initial single anti-Apo B column turned out to be too much of a charge for the extracorporeal circulation, it was split into four smaller columns loaded sequentially; however with neither technique the target volumes could be reached. Thus repetitive-cycling was developed, loading one column and adsorbing the other simultaneously. This technique turned out to be ideal for the patient as it combined specificity, highest possible capacity and optimal economy. Years later other techniques were developed. They all suffer from the disadvantage of limited capacity either in a way that due to their semi-selectivity proteins not associated with the process of athero-sclerosis are removed to an unacceptable extent, or that single columns e.g. whole blood perfusion even if they are loaded sequentially being uneconomic as well. Nevertheless, all manufacturers did not hesitate to steal the original name mainly to hide the disadvantage of their own procedure. The semantic confusion refers
1473-0502/$ - see front matter Ó 2013 Published by Elsevier Ltd. http://dx.doi.org/10.1016/j.transci.2013.03.009
mainly for single use techniques such as precipitation, filtration or whole blood perfusion. Other procedures applying our repetitive cycling technique lack specificity. Another type of confusion at least in Germany originated from guidelines permitting the use of semi selective procedures if they decreased the Cholesterol by only 60%. It is obvious that a decrease of 60% total Cholesterol in a patient with a pre-treatment value of more than 1.000 mg/dl is not acceptable. Also, the synthesis rate needs to be taken into account. A decrease of only 60% in a patient with a high synthesis rate is not adequate. Treating seven homozygous patients at present only two of them do not reach normal values due to their high synthesis rate. Alternatively, 38 heterozygous patients do reach normal values provided they allow for a weekly treatment. Even lower values are obtained in a group of four patients who were informed that after multiple stents and two coronary bypass surgeries only symptomatic therapy could be applied. Standard diagnostic procedures are used to establish the indication for LDL-Apheresis, however survival is the best proof of treatment efficacy. Since 1980 no patient died of his coronary heart disease or any myocardial infarction, the median survival of the homozygous patients is at present 44,3 years (the oldest being 64 years), of the Heterozygotes 64,5 (the oldest being 80 years). In summary LDL-Apheresis differs considerably from LDL-elimination procedures, the decrease as expressed in percentage should be replaced from target values and the patient’s best proof of treatment efficacy is his long term survival.
Contents lists available at SciVerse ScienceDirect
Transfusion and Apheresis Science journal homepage: www.elsevier.com/locate/transci
The lower the better: Target values after LDL-Apheresis and semi-selective LDL-elimination therapies Helmut Borberg German Haemapheresis Centre, Cologne, Germany
LDL-Apheresis was developed in Cologne and introduced into the clinical routine in 1980. The clinical value was supposed to be based on a controlled clinical trial (Statin vs. LDL-Apheresis vs. a combination of both) however instead the German Federal Ministry of Health granted an open multicentre trial at five German universities demonstrating that lowering of the total cholesterol to a value of 100–150 mg/dl post-treatment over a period of 3 years lead to a prevention of progression. Nevertheless, with a subsequent trial on a limited group of patients treated with LDL-Apheresis and Statins, we could demonstrate that the post-treatment synthesis rate could be lowered, if the medication was tolerated. As the initial single anti-Apo B column turned out to be too much of a charge for the extracorporeal circulation, it was split into four smaller columns loaded sequentially; however with neither technique the target volumes could be reached. Thus repetitive-cycling was developed, loading one column and adsorbing the other simultaneously. This technique turned out to be ideal for the patient as it combined specificity, highest possible capacity and optimal economy. Years later other techniques were developed. They all suffer from the disadvantage of limited capacity either in a way that due to their semi-selectivity proteins not associated with the process of athero-sclerosis are removed to an unacceptable extent, or that single columns e.g. whole blood perfusion even if they are loaded sequentially being uneconomic as well. Nevertheless, all manufacturers did not hesitate to steal the original name mainly to hide the disadvantage of their own procedure. The semantic confusion refers
1473-0502/$ - see front matter Ó 2013 Published by Elsevier Ltd. http://dx.doi.org/10.1016/j.transci.2013.03.009
mainly for single use techniques such as precipitation, filtration or whole blood perfusion. Other procedures applying our repetitive cycling technique lack specificity. Another type of confusion at least in Germany originated from guidelines permitting the use of semi selective procedures if they decreased the Cholesterol by only 60%. It is obvious that a decrease of 60% total Cholesterol in a patient with a pre-treatment value of more than 1.000 mg/dl is not acceptable. Also, the synthesis rate needs to be taken into account. A decrease of only 60% in a patient with a high synthesis rate is not adequate. Treating seven homozygous patients at present only two of them do not reach normal values due to their high synthesis rate. Alternatively, 38 heterozygous patients do reach normal values provided they allow for a weekly treatment. Even lower values are obtained in a group of four patients who were informed that after multiple stents and two coronary bypass surgeries only symptomatic therapy could be applied. Standard diagnostic procedures are used to establish the indication for LDL-Apheresis, however survival is the best proof of treatment efficacy. Since 1980 no patient died of his coronary heart disease or any myocardial infarction, the median survival of the homozygous patients is at present 44,3 years (the oldest being 64 years), of the Heterozygotes 64,5 (the oldest being 80 years). In summary LDL-Apheresis differs considerably from LDL-elimination procedures, the decrease as expressed in percentage should be replaced from target values and the patient’s best proof of treatment efficacy is his long term survival.