Lipoprotein apheresis is an optimal therapeutic option to reduce increased Lp(a) levels.

BACKGROUND: Lipoprotein(a) (Lp(a)) is a genetic risk factor for cardiovascular disease (CVD) and is associated with the induction and sustaining of atherosclerotic cardiovascular diseases (ASCVD). Since 2008 Lp(a) along with progressive CVD has been approved as an indication for regular lipoprotein apheresis (LA) in Germany. The German Lipoprotein Apheresis Registry (GLAR) has been initiated to provide statistical evidence for the assessment of extracorporeal procedures to treat dyslipidemia for both LDL-cholesterol (LDL-C) and Lp(a). The GLAR now allows prospective investigations over a 5-year period about annual incidence rates of cardiovascular events. Here Lp(a) patients (LDL-C < 100 mg/dl; Lp(a) > 60 mg/dl or >120 nmol/l) showed the same reduction of major coronary (83%) and non-coronary events (63%) as had been formerly shown in the Pro(a)LiFe study. However, Lp(a) is not only an apolipoprotein(a) (apo(a)) and LDL-C containing particle, which is covalently bound to a LDL-C core by a disulphide bridge. The composition of this particle, inter alia containing oxidized phospholipids, gives pro-atherosclerotic, pro-inflammatory, and pro-thrombotic properties, inducing atherosclerotic processes mainly in the arterial wall. However, recent investigations have shown that a reduction of inflammatory settings without LDL-C or Lp(a) reduction may reduce ASCVD events. Lipoprotein apheresis (LA) could not only reduce LDL-C and Lp(a) in parallel, but also different inflammatory and coagulation parameters. In summary lipoprotein apheresis is not only anti-atherosclerotic, but also anti-inflammatory and anti-thrombotic and therefore an ideal treatment option with respect to the shown reduction of major adverse coronary events (MACE) and major adverse non-coronary events (MANCE) by reducing Lp(a) levels.

Current insights into the German lipoprotein apheresis standard: PCSK9-inhibitors, lipoprotein apheresis or both?

According to current European guidelines, lipid lowering therapy for progressive cardiovascular disease including cardiovascular events has to be focused on a target level for LDL-C. In contrast for Lp(a) a threshold has to be defined with respect to the method of measurement. However, due to new lipid lowering drug developments like PCSK9-inhibitors (PCSK-9-I) a therapeutic algorithm for patients with severe hypercholesterolemia or isolated Lipoprotein(a)-hyperlipoproteinemia with progressive cardiovascular disease may be necessary to manage the use of PCSK9-I, lipoprotein apheresis (LA) or both. The therapeutic approach for patients with homozygous familial hypercholesterolemia is unambiguous: In addition to LA, in order to improve LDL-C reduction, PCSK9-I could be applied. In patients with heterozygous familial hypercholesterolemia, PCSK9-I is to be applied first. If in addition to a pronounced LDL-C elevation, cardiovascular complications exist or if imaging techniques documented atherosclerotic changes pre-disposing for a cardiovascular event while LDL-C reduction is insufficiently reduced (LDL-C > 100 mg/dl (2.6 mmol/l)), LA treatment should then be applied as last resort. In patients with elevated Lp(a) concentrations (Lp(a) > 60 mg/dl (>120 nmol/l)) and established cardiovascular disease, therapy should rely primarily on LA methods. If in addition to high Lp(a) levels insufficiently treated LDL-C concentrations (LDL-C > 100 mg/dl (2.6 mmol/l)) exist, in rare cases PCSK9-I can supplement the lipid lowering concept.

Current insights into the German Lipoprotein Apheresis Registry (GLAR) - Almost 5 years on.

BACKGROUND: In recent years the Federal Joint Committee (G-BA), a paramount decision-making body of the German health care system required a reassessment of the approval of chronic lipoprotein apheresis therapy for regular reimbursement. Since 2005 an interdisciplinary German apheresis working group has been established by members of both German Societies of Nephrology. In 2009 the working group completed the indication for lipoprotein apheresis with respect to current cardiovascular guidelines and current scientific knowledge for the registry. In 2011 the German Lipoprotein Apheresis Registry (GLAR) was launched and data acquired over nearly 5 years can now be reported. METHODS AND RESULTS: All data were collected and analyzed during the time period 2012-2015. Over this time interval, 68 German apheresis centers collected retrospective and prospective observational data of 1.283 patients undergoing lipoprotein apheresis (LA) treatment of high LDL-cholesterol (LDL-C) levels and/or high lipoprotein(a) (Lp(a)) levels suffering from progressive cardiovascular disease (CVD). A total of 15,167 documented LA treatments were investigated. All patients treated by LA exhibited a median LDL-C reduction rate of 68.6%, and a median Lp(a) reduction rate of 70.4%. Analogue to the Pro(a)LiFe pattern, patient data were analyzed and compared with respect to the incidence rate of coronary events (MACE) 1 and 2 years before the start of LA treatment (y-2 and y-1) and prospectively one year on LA treatment (y+1). During the first year of LA treatment a MACE reduction of 97% was be observed. In the years considered, LA treatment side effects occurred at a low rate (ca. 5%) and mainly comprised puncture problems. CONCLUSIONS: For the first time data generated by the GLAR shows that LA lowers the incidence rate of cardiovascular events in patients with high LDL-C and/or high Lp(a) levels, progressive CVD and maximally tolerated lipid lowering medication. In addition LA treatments were found to be safe, exhibiting a low rate of side effects.

The German Lipoprotein Apheresis Registry (GLAR) - almost 5 years on.

BACKGROUND: Since 2005 an interdisciplinary German apheresis working group has been established by members of both German Societies of Nephrology and of Lipidologists and completed the data set for the registry according to the current guidelines and the German indication guideline for apheresis in 2009. In 2011 the German Lipoprotein Apheresis Registry (GLAR) was launched and data are available over nearly 5 years now. METHODS AND RESULTS: During the time period 2012-2016, 71 German apheresis centers collected retrospective and prospective observational data of 1435 patients undergoing lipoprotein apheresis (LA) treatment of high LDL-C levels and/or high Lp (a) levels suffering from cardiovascular disease (CVD) or progressive CVD. A total of 15,527 completely documented LA treatments were entered into the database. All patients treated by LA showed a median LDL-C reduction rate of 67.5%, and a median Lp (a) reduction rate of 71.1%. Analog to the Pro(a)LiFe pattern, patient data were analyzed to the incidence rate of coronary events (MACE) 1 and 2 years before the beginning of LA treatment (y-2 and y­1) and prospectively two years on LA treatment (y + 1 and y + 2). During two years of LA treatment a MACE reduction of 78% was observed. In the years considered, side effects of LA treatment were low (5.9%) and mainly comprised puncture problems. CONCLUSIONS: The data generated by the GLAR shows that LA lowers the incidence rate of cardiovascular events in patients with high LDL-C and/or high Lp (a) levels, progressive CVD, and maximally tolerated lipid lowering medication. In addition, LA treatments were found to be safe with a low rate of side effects.

Therapeutic plasmapheresis and haemostatic system.

The influence of therapeutic plasmapheresis by using membrane filter was investigated in 38 patients with 108 procedures. Fibrinogen and AT III reached most pronounced reduced levels in the course of three plasma exchanges while factors II, V, X, Hepato-Quick, Reptilase time and thrombocyte count remained relatively unchanged. There was no bleeding or thrombotic event in the patients. We concluded that at least determination of fibrinogen and AT III levels must be done just prior to each individual plasmapheresis to prevent dangerous imbalances in haemostatic system.