Lipoprotein Apheresis Treatments Research Articles

Beyond cholesterol-pleiotropic effects of lipoprotein apheresis.

Cardiovascular disease is a leading cause of mortality worldwide, which is caused mainly by atherosclerosis, a chronic inflammatory disease of blood vessels. Therefore, atherosclerosis represents a complex disorder, which induces damage or imbalance on different levels: for example, genes, cytokines, lipoproteins, cells, vessels, and organs. Lipoprotein apheresis (LA) is a well-established extracorporeal treatment of severe hyperlipoproteinemia. In addition, LA may have simultaneously crucial effects on many other atherogenic factors during the treatments, for example, as vascular inflammation, rheology, mobilization of adult stem cells and gene expressions in blood or endothelial cells, which will be discussed in this short review. In addition, stable microRNAs besides tissues also appear in extracellular compartments, for example, vessels, involved in atherosclerotic processes, were found to be reduced by LA treatments. In summary, LA represents a complex therapeutic procedure, that provides an ideal tool for the treatment of complex disorders such as atherosclerosis.

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

BackgroundAlthough 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. MethodsBased 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. ResultsWorking 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. ConclusionsIncidence 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.

High serum triglyceride concentrations in patients with homozygous familial hypercholesterolemia attenuate the efficacy of lipoprotein apheresis by dextran sulfate adsorption

Background and aimsMaximizing the acute reduction of LDL-cholesterol (C) and lipoprotein (a) (Lp(a)) concentrations in patients with homozygous familial hypercholesterolemia (HoFH) is the main goal of lipoprotein apheresis (LA). The objective of this study was to examine how the pre-LA serum TG concentrations influence the efficacy of LA to acutely reduce LDL-C and Lp(a) concentrations in HoFH patients. MethodsData from 1761 LA treatments of HoFH patients (n = 10) and compound heterozygous patients (n = 5) collected between 2008 and 2016 were analyzed. These data included the pre- and post-LA concentrations of LDL-C, TGs and Lp(a); volume of filtered plasma; type of LA system used (dextran sulfate adsorption (DSA) or heparin-induced extracorporeal LDL precipitation (HELP)); and interval between treatments. ResultsA significant association between the pre-LA TG concentrations and acute LA-induced reduction in LDL-C, modified by the type of LA system used, was observed (ppre-LA TG quartile*LA system = .04). Using the DSA system, the acute reduction of the LDL-C concentrations was attenuated by 3.9% when the pre-LA TG concentrations were >2.09 mmol/L vs. ≤0.93 mmol/L (highest vs. lowest quartiles: −59.4% vs. −63.3%, p = .007). Using the HELP system, no significant difference was observed in the reduction of LDL-C between the highest and the lowest quartiles of serum TGs (−65.8% vs. −66.4%, p = .9). No association was observed between pre-LA TG concentrations and acute LA-induced decrease in Lp(a) (p = .2). ConclusionsThe efficacy of LA is inversely associated with pre-LA TG concentrations in HoFH patients who used the DSA system instead of the HELP system.

Vascular access in lipoprotein apheresis: a retrospective analysis from the UK's largest lipoprotein apheresis centre.

Lipoprotein apheresis (LA) has proven to be an effective, safe and life-saving therapy. Vascular access is needed to facilitate this treatment but has recognised complications. Despite consistency in treatment indication and duration there are no guidelines in place. The aim of this study is to characterise vascular access practice at the UK's largest LA centre and forward suggestions for future approaches. A retrospective analysis of vascular access strategies was undertaken in all patients who received LA treatment in the low-density lipoprotein (LDL) Apheresis Unit at Harefield Hospital (Middlesex, UK) from November 2000 to March 2016. Fifty-three former and current patients underwent 4260 LA treatments. Peripheral vein cannulation represented 79% of initial vascular access strategies with arteriovenous (AV) fistula use accounting for 15%. Last used method of vascular access was peripheral vein cannulation in 57% versus AV fistula in 32%. Total AV fistula failure rate was 37%. Peripheral vein cannulation remains the most common method to facilitate LA. Practice trends indicate a move towards AV fistula creation; the favoured approach receiving support from the expert body in this area. AV fistula failure rate is high and of great concern, therefore we suggest the implementation of upper limb ultrasound vascular mapping in all patients who meet treatment eligibility criteria. We encourage close ties between apheresis units and specialist surgical centres to facilitate patient counselling and monitoring. Further prospective data regarding fistula failure is needed in this expanding treatment field.

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

BackgroundIn 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 resultsAll 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. ConclusionsFor 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) \u2013 almost 5\xa0years on

BackgroundSince 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 resultsDuring 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 y‑1) 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.ConclusionsThe 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.

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.

Impact of the German Lipoprotein Apheresis Registry (DLAR) on therapeutic options to reduce increased Lp(a) levels.

BackgroundThe German Lipoprotein Apheresis Registry (DLAR) has been initiated by members of the Nephrology Foundation (WiNe), the German association of kidney centres (DN), the German society of nephrology (DGfN) and additional medical associations taking part in the apheresis working group. Its goal is the introduction of a substantial database, suitable to provide statistical evidence for the assessment of extracorporeal procedures. Data have been added to the DLAR since October 2011. In this article, preliminary results are first reported.Methods and resultsData are stored on a secured Internet platform. The recorded information comprises mean values and rates of change in lipid levels (cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, lipoprotein(a) (Lp(a)) before and after apheresis therapy, blood/plasma volume, frequency and type of adverse effects, medication, vascular events, diagnoses and comorbidity. It is collected by participating apheresis centres from all over Germany. Up until October 2014, a total of 7946 lipoprotein apheresis (LA) treatments of 991 patients (787 with documented LDL-C and 688 with documented Lp(a) levels) via 96 medical accounts were documented and analysed. The current share of Lp(a) patients is 50.6 % (Lp(a) ≥ 60 mg/dl; n = 348/688). For both LDL-C and Lp(a), lowering rates exceeding 60 % have been observed. Likely in conjunction with these reduction rates, the preliminary analysis shows a 90 % decline in major adverse coronary events (MACE) as well as a decrease in major adverse non-coronary events (MANCE) by 69 %. As before, good tolerability and low rates of adverse effects (< 3 %) of LA therapy were found.ConclusionsThe available numbers suggest in parts very good response by the participating centres to the DLAR. Unfortunately, there are also centres that have not documented any patients so far or LA treatments at all. The benchmark values for reduction rates in lipoprotein concentration required by the directives of the German Federal Joint Committee (G-BA) have all been met. The decrease in MACE and MANCE rates currently observed is very promising. However, the comparably short runtime of the registry does not allow for high confidence in the current results. Certainly, reliable data will be extractable in the coming years. Given the high interest expressed by European neighbours, the extension of the registry to the European level should be a future goal for the DLAR as well.

Lipoprotein apheresis – More than just cholesterol reduction?

Lipoprotein apheresis is a well-established extracorporeal treatment in modality of severe hyperlipoproteinemia. Besides the reduction of LDL cholesterol and modifications to physiology of lipoprotein and lipid metabolism, Lipoprotein apheresis may have crucial effects on many other atherogenic factors as vascular inflammation, rheology and gene expressions in blood cells. These different effects of lipoprotein apheresis treatments are reviewed with respect to oxidative stress in plasma, red and white blood cells and in consequence to progression of atherosclerosis. However, in consideration of these reviewed aspects as a factor of biocompatibility lipoprotein apheresis remains safe.