The German Lipoprotein Apheresis Registry-Summary of the ninth annual report.

During 2012-2020, 89 German apheresis centers collected retrospective and prospective observational data of 2028 patients undergoing regular lipoprotein apheresis (LA) for the German Lipoprotein Apheresis Registry (GLAR). More than 47 500 LA sessions are documented in GLAR. In 2020, all patients treated with LA showed a high immediate median reduction rate of LDL-C (68.2%, n = 1055) and Lp(a) (72.4%, n = 994). Patient data were analyzed for the incidence rate of major coronary events (MACE) 1 and 2 years before the beginning of LA treatment (y-2 and y-1) and prospectively up to 7 years on LA (y + 1 to y + 7). During the first 2 years of LA (y + 1 and y + 2), a MACE reduction of 78% was observed. Current analysis of GLAR data shows very low incidence rates of cardiovascular events in patients with high LDL-C and/or high Lp(a) levels, progressive ASCVD, and maximally tolerated lipid lowering medication regular by LA results.

Lipoprotein(a) - Marker for cardiovascular risk and target for lipoprotein apheresis.

Lipoprotein(a) (Lp(a)) consists of an LDL particle whose apolipoprotein B (apoB) is covalently bound to apolipoprotein(a) (apo[a]). An increased Lp(a) concentration is a causal, independent risk factor for atherosclerotic cardiovascular disease (ASCVD) and a predictor of incident or recurrent cardiovascular events. Although Lp(a) was first described as early as 1963, only the more recent results of epidemiological, molecular, and genetic studies have led to this unequivocal conclusion. More than 20% of Western populations have elevated Lp(a) values. Lp(a) concentrations should be always part of the lipid profile when ASCVD risk is assessed. However, presence of other risk factors, laboratory findings, medical history and family history must be considered to conclude on its clinical relevance in an individual patient. Early or progressive ASCVD or a familial predisposition are key findings which can be associated with elevated Lp(a). The cholesterol portion contained in Lp(a) is also included in the various methods of LDL-C measurement. To assess proximity to the cardiovascular risk related target value for LDL-C, appropriate correction should be applied when high Lp(a) values are obtained to estimate the LDL-C that can actually be treated by lipid lowering drugs. Initial study data show that antisense oligonucleotides, which selectively decrease apolipoprotein(a), are promising as future treatment options. Currently, lipoprotein apheresis, which has a reimbursement guideline in Germany, is the therapy of choice for patients with Lp(a)-associated progressive ASCVD, with the aim of sustained prevention of further cardiovascular events.

Lipoprotein apheresis in Germany - Still more commonly indicated than implemented. How can patients in need access therapy?

BACKGROUND: Although lipid-lowering drugs, especially statins, and recently also PCSK9 inhibitors can reduce LDL cholesterol (LDL-C) and decrease the risk for cardiovascular disease (CVD) including coronary artery disease (CAD) events most efficiently, only 5-10% of high-risk cardiovascular patients reach the target values recommended by international guidelines. In patients who cannot be treated adequately by drugs it is possible to reduce increased LDL-C and/or lipoprotein(a) (Lp(a)) values by the use of lipoprotein apheresis (LA) with the potential to decrease severe CVD events in the range of 70%->80%. Even in Germany, a country with well-established reimbursement guidelines for LA, knowledge about this life-saving therapy is unsatisfactory in medical disciplines treating patients with CVD. Starting in 1996 our aim was to offer LA treatment following current guidelines for all patients in the entire region of our clinic as standard of care. METHODS: Based on the experience of our large apheresis competence center overlooking now nearly 80,000 LA treatments in the last two decades, we depict the necessary structure for identification of patients, defining indication, referral, implementation and standardisation of therapy as well as for reimbursement. LA is unfamiliar for most patients and even for many practitioners and consultants. Therefore nephrologists performing more than 90% of LA in Germany have to form a network for referral and ongoing medical education, comprising all regional care-givers, general practitioners as well as the respective specialists and insurances or other cost bearing parties for offering a scientifically approved therapeutic regimen and comprehensive care. The German Lipid Association (Lipid-Liga) has implemented the certification of a lipidological competence center as an appropriate way to realize such a network structure. RESULTS: Working as a lipidological and apheresis competence center in a region of 400,000 to 500,000 inhabitants, today we treat 160 patients in the chronic LA program. In spite of the availability of PCSK9 inhibitors since 2015, LA has remained as an indispensable therapeutic option for targeted lipid lowering treatment. An analysis of nearly 37,000 LA treatments in our own center documented a >80% reduction of cardiovascular events in patients treated by regular LA when comparing with the situation before the start of the LA therapy. We have implemented the concept of an apheresis competence center characterised by ongoing medical education with a focus on lipidological and cardiovascular aspects, interdisciplinary networking and referral. CONCLUSIONS: Incidence and prevalence of LA patients in our region demonstrate that based on our ongoing patient-centered approach the access of patients in need to LA is substantially above the German average, thus contributing to an extraordinary reduction of cardiovascular events in the population we in particular feel responsible for.

Lipidological competence centres and networks: Future perspectives to improve healthcare of patients with disorders of lipid metabolism.

BACKGROUND: Numerous healthcare studies have shown that more than 90% of all patients with dyslipidaemia are not treated adequately. OBJECTIVES: The "Deutsche Gesellschaft zur Bekämpfung von Fettstoffwechselstörungen und ihren Folgeerkrankungen (DGFF)" [German Society of Lipidology], a non-profit professional membership organization, has already made a series of efforts to improve the care of patients suffering from dyslipidaemia. A recent outcome is the nationwide implementation and certification of Lipidological Competence Centres and Networks (LCCNs). METHODS AND RESULTS: By involving numerous external medical cooperation partners and combining the detailed work of different in-house medical specialists, the Medical Care Centre Kempten-Allgäu was able to improve both the diagnosis and treatment of patients exhibiting disorders of lipid metabolism (DLM). This local lipidological network is so successful, that it may serve as a nationwide standard model for outpatient lipidological care. Detailed organizational structures for improved lipidological care which are suitable to provide a template for future guidelines for the certification of LCCNs have been developed by the Medical Care Centre Kempten-Allgäu. Stringent requirements of implementation with respect to medical staff, content and structure, staff training, patient education and public relations as well as to documentation, quality assurance and quality improvement must be fulfilled both by the lipidological competence centre (LCC) and the cooperation partners within the lipidological network (LN). Finally, members of the health care system (e.g. health policy and health insurances) should be involved in this attempt and convinced of financial support. CONCLUSION: The implementation and certification of national LCCNs supported by DGFF could contribute to a comprehensive improvement in the care of patients with dyslipidaemia, resulting in prevention of cardiovascular diseases and reduction of cardiovascular sequelae.

Lipid apheresis techniques: current status in Germany.

For long-term lipid apheresis therapy, several different technical systems have been developed which enable effective reduction of LDL cholesterol and other atherogenic lipoproteins, such as Lp(a), with sufficient selectivity and good clinical tolerance. Suitable techniques include whole blood adsorption with polyacrylamide and dextran sulfate cellulose, while primary plasma separation is used for cascade filtration, heparin-induced precipitation, immunoadsorption, silicate gel adsorption, and dextran sulfate cellulose (both techniques). The technical features are described. Only intensive training and experience of the medical personnel guarantees reliable treatment safety of all systems at a very low rate of minor side effects.