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.

Efficacy, safety, and tolerability of long-term lipoprotein apheresis in patients with LDL- or Lp(a) hyperlipoproteinemia: Findings gathered from more than 36,000 treatments at one center in Germany.

LDL cholesterol (LDL-C) and lipoprotein(a) (Lp(a)) are main risk factors for cardiovascular disease (CVD). Efficacy, safety, and tolerability of lipoprotein apheresis (LA) were investigated in 36,745 LA treatments of 118 patients with CVD in a retrospective, monocentric study. Indications were severe hypercholesterolemia (n = 83) or isolated Lp(a) hyperlipoproteinemia (n = 35). Average age of patients at start of LA treatment was 58.1 years for males and 62.5 years for females. Medium interval between the first cardiovascular event and LA treatment was 6.4 ± 5.6 years and the average LA treatment period was 6.8 ± 4.9 years. On average treatments were performed once a week, via peripheral venous access in 79.3% of non-hemodialysis patients. In patients with hypercholesterolemia initial pre-LA LDL-C was lowered from 176.4 ± 67.0 mg/dL by 66.7 ± 10.8% per session, achieving a long-term interval mean value of 119.8 ± 34.7 mg/dL, i.e. reduction by 32.1 ± 19.6% (p < 0.0001). In patients with isolated elevated Lp(a) initial pre-LA Lp(a) was lowered from 127.2 ± 67.3 mg/dL by 66.8 ± 5.8% per session, achieving a long-term interval mean value of 60.0 ± 19.5 mg/dL, i.e. reduction by 52.8 ± 23.0% (p < 0.0001). After start of LA the average annual rate of major adverse coronary events (MACE) of all patients declined by 79.7% (p < 0.0001). Subgroup analysis showed decline by 73.7% (p < 0.0001) in patients with severe hypercholesterolemia, and by 90.4% (p < 0.0001) in patients with isolated elevated Lp(a). Adverse events (AE) occurred in 1.1% of treatments. LA treatment of patients with high risk for CVD due to LDL and/or Lp(a) hyperlipoproteinemia was effective, safe, and well tolerated. The number of cardiovascular events, at least during a six-year period, declined by 80%.

Clinical benefit of long-term lipoprotein apheresis in patients with severe hypercholesterolemia or Lp(a)-hyperlipoproteinemia with progressive cardiovascular disease.

Low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) (Lp(a)) are established causal risk factors for cardiovascular disease (CVD). Efficacy, safety, and tolerability of lipoprotein apheresis (LA) were investigated in 118 patients with CVD covering a period with 36,745 LA treatments in a retrospective, monocentric study. Indications for LA were severe hypercholesterolemia (n = 83) or isolated Lp(a) hyperlipoproteinemia (Lp(a)-HLP) (n = 35). In patients with hypercholesterolemia, initial pre-LA LDL-C was 176.4 ± 67.0 mg/dL. In patients with isolated Lp(a)-HLP, initial pre-LA Lp(a) was 127.2 ± 67.3 mg/dL. Mean reduction rates of LA were 67 % for both LDL-C and Lp(a). During chronic LA, the average annual rate of major adverse cardiac events of all patients declined by 79.7 % (p < 0.0001). Subgroup analysis showed decline by 73.7 % (p < 0.0001) in patients with severe hypercholesterolemia, and by 90.4 % (p < 0.0001) in patients with isolated Lp(a)-HLP. Adverse events occurred in 1.1 % of treatments. LA treatment of patients with a high risk for CVD due to hypercholesterolemia and/or Lp(a)-HLP demonstrated clinical benefit and was safe and well tolerated.

Indication and implementation of lipidapheresis, rheopheresis, or immunoadsorption (lessons learnt from Germany's largest apheresis center).

Efficient modes of extracorporeal blood purification are available today for apheresis treatment of progressive atherosclerosis, autoimmune disease, or for improving hemorheology. Advanced technology and sophisticated care render apheresis treatment selective, safe and tolerable. Our task is to constantly update indications for apheresis based on best evidence available and good clinical practice, as well as, to determine how apheresis therapy can be made available to those in need or with otherwise refractory disease. Presenting examples of lipid apheresis, rheopheresis, or immunoadsorption for treatment of hypercholesterolemia, hyperlipoproteinemia (a), acute hearing loss, refractory or exacerbating multiple sclerosis, we highlight real world obstacles for implementation of treatment, resulting in still too many patients with proven or recommended indication left untreated. Based on the experience of the largest apheresis center in Germany, with more than 3,300 treatments per year, we depict the necessary structure for identification of patients, defining indication, referral, implementation of therapy, and reimbursement. Apheresis is unfamiliar to most patients and many practitioners or consultants. Nephrologists, performing >90% of apheresis treatments in Germany, have to form a network for referral comprising all regional care-givers, general practitioners as well as the respective specialists (mainly, cardiologists, endocrinologists, diabetologists, ORL specialists, neurologists, ophthalmologists, or rheumatologists), and insurances or other cost-bearing parties for offering a scientifically approved therapeutic regimen and comprehensive care. We have realized this concept in a high volume apheresis center acting in a closely knit network characterized by an unrelenting effort at ongoing medical education. As a consequence, we include approximately 10 times more patients with appropriate diagnoses in our apheresis program as compared to the national average.