Lipoprotein Apheresis Research Articles

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.

One year follow-up of patients with reduced left ventricular ejection fraction (LVEF) on lipoprotein apheresis

BackgroundLeft ventricular ejection fraction (LVEF) is a valuable measure to assess left ventricular systolic function. Lipid lowering therapy by statins has been shown to have an impact on LVEF already after a 6 months treatment. Higher doses of statins have been claimed to be more effective as compared to a conventional one and even a difference between lipophilic and hydrophilic compounds has been reported. The effect of regular lipoprotein-apheresis (LP-apheresis) on LVEF was previously poorly examined.Patients involved in a regular LP-apheresis program are supposed to undergo a number of follow-up investigations among them myocardial scintigraphy and LVEF, measured by radionuclide ventriculography. MethodsWe examined 18 patients before initiation and after one year of ongoing LP-apheresis. 13 patients (11 males, 2 females, mean age 58.3 ± 5.3 years, groups A) were since more than a year on stable, unchanged statin treatment (atorvastatin 40 mg, simvastatin 40 mg, rosuvastatin 20 mg±ezetimibe), the other 5 patients (3 males, 2 females, mean age 57.1 ± 4.6 years, group B) were intolerant to statins being on micronized fenofibrate±resorption inhibitors (cholestyramine). All patients had a Lp(a) < 30 mg/dl. As part of the usual follow-up monitoring, LVEF was determined by means of radionuclide ventriculography after application of 550 MBq 99m Tc-pertechnetate. ResultsThe follow-up LVEF was checked at a mean of 48.7 weeks in group A and 51.2 weeks in group B. Except in 1 patient (LVEF 46.8% before vs. 45.2% after LP-apheresis initiation) in group A we noted a significant increase in LVEF in 12 patients of group A (92%) and in all patients of group B. Mean LVEF increased significantly in both groups (A: 42.7±8.1 → 46.5±7.5% (p < 0.001) and B: 41.9±8.4 → 46.5±6.3 %; p < 0.001). The relative rise was nearly identical (group A 9.6%, in group B 9.7%). ConclusionsOur findings indicate that regular long-term LP-apheresis treatment apparently increases LVEF, independently on current statin treatment. This implies a role of lowering of atherogenic lipoproteins as underlying mechanism. A prospective study should clarify the relative extent of LVEF improvement induced by LP-apheresis.

Influence of lipoprotein apheresis on circulating plasma levels of miRNAs in patients with high Lp(a)

BackgroundLipoprotein apheresis (LA) is a well-established therapy for lowering lipid levels in serious cases of dyslipidaemia, including high levels of lipoprotein(a) [Lp(a)]. This method lowers both LDL cholesterol and Lp(a) by more than 60% in most of patients; however, because randomized clinical studies could be extremely difficult, also other markers of the effect of this procedures on vascular health are of importance. Therefore, in addition to changes in plasma lipids and Lp(a) during LA, we also analysed the response of biomarkers associated with vascular integrity: small non-coding microRNAs (miRNAs). Materials and methodsWe analysed the changes in miRNAs in two women (age 70 and 72 years) with clinically manifest extensive and progressive atherosclerotic disease and high levels of Lp(a) and with different clinical course who were treated by LA. In both women we analysed changes of 175 circulating plasma miRNAs using pre-defined serum/plasma focus panels at the beginning of and one year after the therapy. ResultsIn addition to reduced levels of plasma lipids and Lp(a), circulating plasma levels of miR-193a-5p; -215-5p; -328-3p; -130a-3p; -362-3p; -92b-3p decreased, and levels of miR-125a-5p; -185-5p; -106a-5p; -320b; -19a increased (all P < 0.05) in both women. Moderate differences were found between both women with regard to the different course of atherosclerotic disease. ConclusionsLong-term LA substantially changes circulating plasma miRNAs associated with vascular integrity reflected different clinical course in both women. If confirmed, this approach could improve the assessment of the effectiveness of this therapy on an individual basis.

Short- and long-term effects of lipoprotein apheresis on plasma hormones in patients with therapy-resistant dyslipidemia

Background and aimsLipoprotein apheresis (LA) is a highly effective method to improve the clinical and metabolic situation in patients with therapy-resistant disorders of lipid metabolism. Cholesterol is the substrate for the synthesis of all steroid hormones. If repeated massive reduction of LDL-cholesterol may interfere with human adrenal steroidogenesis, and could become clinically relevant is unknown, so far. Thus, the aim of this study was to determine possible short- and long-term effects of LA on blood plasma levels of ACTH, cortisol, aldosterone, DHEAS, renin and testosterone. MethodsIn total, 39 patients, treated with one of four LA techniques were studied: 1. Lipid Filtration (LF; n = 7), 2. Dextran Sulfate Adsorption (DSA; n = 7), 3. Membrane Filtration Optimised Novel Extracorporeal Treatment (MONET; n = 8), and 4. Direct Absorption of Lipoproteins (DALI; n = 15). Hormone levels were analyzed before and after five LA sessions with an interval of 20 weeks covering a total observation time of two years. In addition patients were comprehensively characterized by clinical and laboratory data. ResultsPatients treated with LA revealed an acute reduction of steroid hormones and ACTH, independent of apheresis technology but no long-term insufficiency in steroidogenesis was observed. Plasma renin levels were stable in LF patients and were highly elevated in patients under DSA, MONET and DALI apheresis throughout the observation period. ConclusionsIn summary, these data suggest that although different LA techniques considerably differ in their acute effects on hormone levels during LA, they did not alter long-term hormone levels sustainably.

Lipoprotein(a) and Atherosclerotic Cardiovascular Disease: Current Understanding and Future Perspectives.

To review current knowledge of elevated lipoprotein(a) [Lp(a)] levels in relation to atherosclerotic cardiovascular disease (ASCVD) and discuss their potential use as biomarkers and therapeutic approaches in clinical practice. We summarized the current understanding and recent advances in the structure, metabolism, atherogenic mechanisms, standardized laboratory measurement, recommended screening populations, and prognostic value of Lp(a), with a special focus on the current potential treatment approaches for hyperlipoprotein(a)emia in patients with ASCVD. Lp(a) is composed of LDL-like particle and characteristic apolipoprotein(a) [apo(a)] connected by a disulfide bond. Substantial evidence shows that elevated plasma Lp(a) level is a heritable, independent, and possibly causal risk factor for ASCVD through its proatherogenic, proinflammatory, and potentially prothrombotic properties. Current guidelines recommend Lp(a) measurement for patients with an intermediate-high risk of ASCVD, familial hypercholesterolemia, a family history of early ASCVD or elevated Lp(a), and progressive ASCVD despite receiving optimal therapy. Traditional Lp(a)-lowering approaches such as niacin, PCSK9 inhibitors, mipomersen, lomitapide, and lipoprotein apheresis were associated with a non-specific and limited reduction of Lp(a), intolerable side effects, invasive procedure, and high expense. The phase 2 randomized controlled trial of antisense oligonucleotide against the apo(a) encoding gene LPA mRNA showed that IONIS-APO(a)-LRX could specifically reduce the level of Lp(a) by 90% with good tolerance, which may become a promising candidate for the prevention and treatment of ASCVD in the future. It is reasonable to measure Lp(a) levels to reclassify ASCVD risk and manage individuals with elevated Lp(a) to further reduce the residual risk of ASCVD, especially with IONIS-APO(a)-LRX.

Effect of evolocumab on lipoprotein apheresis requirement and lipid levels: Results of the randomized, controlled, open-label DE LAVAL study

Lipoprotein apheresis (LA) can effectively lower lipoproteins but is an invasive procedure. The objective of this study was to evaluate whether evolocumab can reduce LA requirement in patients undergoing chronic LA. Patients on regular weekly or every-2-week LA and moderate- to high-intensity statin (if tolerated) with pre-LA low-density lipoprotein cholesterol (LDL-C) levels ≥2.6mmol/L (100mg/dL) to ≤4.9mmol/L (190mg/dL) were randomized to continue the same LA frequency, or discontinue LA and receive evolocumab 140mg every-2-weeks subcutaneously for 6weeks. At week 6, all patients received only open-label evolocumab for 18weeks. The primary endpoint was LA avoidance at the end of 6weeks based on achieving pre-LA LDL-C <2.6mmol/L at week4. Thirty-nine patients (mean [SD] age 62 [10] years, 59% male, 82% with familial hypercholesterolemia) were randomized (evolocumab, n=19; LA, n=20). At the end of 6weeks, more patients receiving evolocumab avoided LA than those receiving LA (84% vs 10%; treatment difference, 74% [95% CI: 45, 87]; P<.0001). Thirty patients (77%) did not require LA at 24weeks. Evolocumab reduced pre-LA LDL-C by 50% from the baseline to week 4 compared with a 3% increase in the LA arm. Pre-LA LDL-C <1.8mmol/L (70mg/dL) was achieved by 10 patients (53%) receiving evolocumab and none receiving LA (week 4). Safety was comparable between arms. Evolocumab treatment significantly reduced LA requirement in patients undergoing chronic LA. In addition, >50% of patients achieved LDL-C <1.8mmol/L on evolocumab alone, demonstrating that in patients with pre-LA LDL-C ≤4.9mmol/L, evolocumab may replace LA.

Extracorporeal apheresis therapy for Alzheimer disease-targeting lipids, stress, and inflammation.

Current therapeutic approaches to Alzheimer disease (AD) remain disappointing and, hence, there is an urgent need for effective treatments. Here, we provide a perspective review on the emerging role of "metabolic inflammation" and stress as a key factor in the pathogenesis of AD and propose a novel rationale for correction of metabolic inflammation, increase resilience and potentially slow-down or halt the progression of the neurodegenerative process. Based on recent evidence and observations of an early pilot trial, we posit a potential use of extracorporeal apheresis in the prevention and treatment of AD. Apolipoprotein E, lipoprotein(a), oxidized LDL (low density lipoprotein)'s and large LDL particles, as well as other proinflammatory lipids and stress hormones such as cortisol, have been recognized as key factors in amyloid plaque formation and aggravation of AD. Extracorporeal lipoprotein apheresis systems employ well-established, powerful methods to provide an acute, reliable 60-80% reduction in the circulating concentration of these lipid classes and reduce acute cortisol levels. Following a double-membrane extracorporeal apheresis in patients with AD, there was a significant reduction of proinflammatory lipids, circulating cytokines, immune complexes, proinflammatory metals and toxic chaperones in patients with AD. On the basis of the above, we suggest designing clinical trials to assess the promising potential of such "cerebropheresis" treatment in patients with AD and, possibly, other neurodegenerative diseases.

P5365Microsomal triglyceride transfer protein inhibitor (lomitapide) efficacy in the treatment of patients with homozygous familial hypercholesterolemia phenotype

Abstract Introduction The majority of patients with homozygous familial hypercholesterolemia (HoFH) phenotype are treated additionally to lipid lowering (LL) drugs (statin + ezetimibe ± colesevelam) with lipoprotein apheresis (LA) sessions. The aim of this study was to evaluate the effect of microsomal triglyceride transfer protein inhibitor (lomitapide) in HoFH patients. Patients and methods In 12 HoFH patients treated with LL drugs ± biweekly LA sessions (9 patients) the 5–40 mg daily of lomitapide was added. Lipid profile [total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), triglycerides (TG) and high density lipoprotein cholesterol (HDL-C)] before (LL drugs ± LA) and after lomitapide treatment were evaluated. Results The follow-up period of lomitapide treatment for 12 patients was 3–24 months (13.8±7.9). The median baseline LDL-C levels was 1000 mg/dL (339–1150). During LL drug therapy, patients showed a median LDL-C level of 383.5 mg/dL (Range: 214–866 mg/dL) and with LL drugs + Time-averaged levels (CAVG) the median was 288.1 mg/dL (Range: 183.69–716.65 mg/dL). The addition of lomitapide at the average dosage of 21.4 mg/day lowered LDL-C levels by 56.8% comparing to LL drugs alone therapy [mean reduction 262.12, 95% CI (105.53, 418.71), p=0.005] and by 54% [mean reduction −182.89, 95% CI (−342.35, −23.43), p=0.031] comparing to LL drugs + LA (CAVG). The CAVG of LDL-C in LL drugs + LA patients compared with LL drugs + lomitapide was 54% in favour of lomitapide (p=0.031). After lomitapide administration to LL drugs + LA treatment, 78% patients discontinued LA and 2 patients reduced their LA frequency by 50%. During follow-up, 2 patients (16.6%) reported side effects (transient diarrhea, 1 patient had liver transaminase &gt;5× ULN and had to decrease dose of lomitapide). Two patients stopped lomitapide due to diet and alcohol restrictions. Median and ranges of lipid and lipoprotein values before any intervention, after LL drugs, LL drugs plus LA, LL drugs plus LA (CAVG) and LL drugs plus lomitapide Total Cholesterol LDL-C HDL-C Triglycerides Before any intervention 1000 (339–1150) 900 (245–1070) 34.5 (25–50) 125 (87–314) After LL drugs 434 (278–915) 383.5 (214–866) 36 (27–51) 113 (62–198) LL drugs + LA (CAVG) 336.13 (248.57–784.16) 288.07 (183.69–716.65) 42.81 (25.84–46.68) 105.09 (55.79–166.68) LL drugs + Lomitapide 228.5 (118–554) 173.5 (74–515) 37.5 (29–50) 83.5 (23–316) LDL graph Conclusions Treatment with lomitapide in HoFH patients has beneficial effect with constant decrease of LDL-C by 57% compared with classical LL therapy and by 54% compared with classical LL therapy and CAVG and seems to be with good safety profile. Although, in some cases the hybrid (all availably drug treatment and LA) therapy may be needed.

P650Lipopolysaccharide-nuclear factor-kappa B pathway and lipoprotein apheresis effects in patients with familial hypercholesterolemia and coronary artery disease

Abstract Abstract Background Inflammation may play an important role in atherosclerosis in familial hypercholesterolemia (FH). Lipopolysaccharide (LPS)-nuclear factor-kappa B (NF-κB) pathway is a routine signal process activated in inflammatory status. Purpose This study aimed to examine the LPS-NF-κB axis status and the impact of lipoprotein apheresis (LA) on this pathway in patients with FH and coronary artery disease (CAD). Methods In this matched case-control study a genetically diagnosed FH cohort who presented stable CAD (n=63) was compared with 63 non-FH CAD and 63 non-FH non-CAD controls matched by sex and age. Plasma LPS levels and NF-κB activity were compared among the three groups. In addition, we studied in vitro LPS-induced interleukin-6 (IL-6) production by mononuclear cells from 16 FH cases without previous statin use and compared them with their respective matched control groups. Subsequently, these 16 FH patients underwent LA. Blood samples were taken immediately before and regularly after LA for measuring LPS and NF-κB. Results FH plus CAD had higher LPS levels and NF-κB activity than CAD and non-CAD controls (all p values &lt;0.01). LPS-induced IL-6 production by mononuclear cells of FH plus CAD was also much higher compared with CAD and non-CAD controls (both p values &lt;0.01). Moreover, plasma LPS levels (p&lt;0.001) and NF-κB activity (p&lt;0.01) were dramatically reduced after apheresis in FH patients. Conclusion Genetically confirmed FH patients with CAD had a marked activation of LPS-NF-κB axis, while LA significantly attenuated this key inflammatory pathway, suggesting that inflammation may be an important therapeutic target for FH patients.

Lipoprotein aferezi homozigot ailevi hiperkolesterolemi hastalarında ventriküler repolarizasyonu etkiler

Aim: Patients with Homozygous Familial Hypercholesterolemia (HoFH) prone to experience premature cardiovascular disease and often die from sudden cardiac death (SCD) at a young age. Lipoprotein apheresis (LA) is the treatment of choice to prolong survival. Several mechanisms has been suggested to be responsible for the known short and long-term clinical benefits of this procedure. This study was conducted to assess the effect of single LA on ventricular repolarization parameters in patients with HoFH.Material and Methods: Eleven patients (mean age 30.1 ± 5.5 years, male 63.6%) with HoFH on chronic LA treatment were enrolled in this preliminary study. Double filtration plasmapheresis (DFPP) was performed in all patients. To examine the effects of a single session of LA, on ventricular repolarization, the OT, QTc interval, the T peak-to-end (Tp-e) interval, Tp-e/QT and the Tp-e/QTc ratio were specifically calculated.Results: The single session of LA reduced total LDL (from 10.04 ± 1.91 to 4.16 ± 1.21 mmol/L, P&amp;lt;001). The heart rate did not change significantly after LA session. Plasma levels of calcium and magnesium was significantly decreased after the procedure. The QTc decreased from 443.8 ± 23.3 ms to 412.3 ± 20.0 ms (P &amp;lt;0.001). The Tp-e interval and the Tp-e/QTc ratio decreased significantly [85 (70-89) ms vs. 63 (58-71)ms; P =0.003, and 0.19 (0.16-0.20) vs 0.15 (0.13-0.16); P =0.003, respectively]. Conclusion: Our data suggest that even a single session of LA improved electrocardiographic repolarization indexes.

Autosomal recessive hypercholesterolemia: Case report

Autosomal recessive hypercholesterolemia (ARH; OMIM #603813) is a very rare monogenic disorder affecting less than 1 in 1000,000 people and is characterized by very high levels of low-density lipoprotein cholesterol (LDL-C), leading to aggressive and premature atherosclerotic cardiovascular disease if left untreated. Lowering of LDL-C is the main target of the treatment. We report on a 29-year-old male patient born in nonconsanguineous Lithuanian family homo(hemi-)zygous for LDLRAP1 gene variant causing ARH. This variant is not present in population databases and, to our knowledge, has not been reported in scientific literature before. The earliest clinical sign, noticed at the age of 5 years, was painful and enlarging nodules on Achilles tendons. At the age of 10 years, xanthomas of the metacarpal joint area on both hands emerged. The first lipid panel was performed at the age of 12 years. In accordance with Dutch Lipid Clinic Network diagnostic criteria for familial hypercholesterolemia (FH), definite FH (type IIA hyperlipoproteinemia) was diagnosed and the treatment with cholestyramine 4 grams per day was initiated. As the patient was 15 years old, direct adsorption of low-density lipoprotein apheresis was started and repeated monthly. At the age of 20 years, along with lipoprotein apheresis, 10 mg of rosuvastatin daily intake was prescribed. At the age of 28 years, the dose of rosuvastatin was increased to 40 mg per day, and 10 mg of ezetimibe daily intake was added. At the age of 28 years, homozygous LDLRAP1 gene variant NM_015627.2:c.488A>C, NP_056442.2:p.(Gln163Pro) causing autosomal recessive hypercholesterolemia was determined by genetic testing. This case report implies that ARH, being an extremely rare disorder, is a severe disease. As there is limited routine testing, including genetic testing, patients suffering from both this disease and FH may remain undiagnosed. Cascade screening and genetic counseling differ for ARH as compared with FH, as the carrier of a pathogenic variant in the LDLRAP1 gene does not have marked total cholesteroland LDL-C elevations. However, genetic testing of the proband and their relatives is essential to evaluate the risk of development of FH and to provide prognosis as well as adequate, timely treatment. To improve the quality of life of patients with FH and prolong their life expectancy, national registries of FH and wider laboratory and genetic testing are undoubtedly necessary. A national FH screening program was set up in Lithuania, which helps to identify, monitor, and treat subjects with FH.

Lipoprotein apheresis for lipoprotein(a) and cardiovascular disease

Elevated lipoprotein(a) [Lp(a)] is an independent risk factor for cardiovascular disease (CVD). In the United States, lipoprotein apheresis (LA) therapy is approved for patients with familial hypercholesterolemia. Germany uses LA therapy for patients with an Lp(a)>60mg/dL, normal low-density lipoprotein cholesterol (LDL-C) levels, and CVD. LA therapy in this population demonstrated a >70% reduction in CVD events. In the United States, LA is only approved for patients with elevated LDL-C levels, regardless of Lp(a) level. The objective of the study was to evaluate clinical significance of Lp(a) reduction with LA therapy in the United States. A retrospective cohort study at one LA site in the United States evaluated 14 CVD patients with elevated Lp(a) and near normal LDL-C levels. Patient data was analyzed to demonstrate possible clinical benefit in reducing Lp(a) levels with LA to mitigate risk of major adverse cardiovascular events. Pre-LA patients' mean LDL-C and Lp(a) were 80mg/dL and 138mg/dL, respectively. LA therapy demonstrated a reduction of mean LDL-C to 29mg/dL and Lp(a) to 51mg/dL. These represent a percent reduction of 64% and 63% for LDL-C and Lp(a), respectively. There was a 94% reduction in major adverse cardiovascular events over a mean treatment period of 48months. The treatment of CVD patients with an elevated Lp(a) and near normal LDL-C with LA in a U.S. treatment center demonstrated a significant reduction in future CVD events. LA should be considered for patients in the United States suffering from an elevated Lp(a) and progressive CVD.

Detection of Lipoprotein X (LpX): A challenge in patients with severe hypercholesterolaemia.

Lipoprotein X (LpX) is an abnormal lipoprotein fraction, which can be detected in patients with severe hypercholesterolaemia and cholestatic liver disease. LpX is composed largely of phospholipid and free cholesterol, with small amounts of triglyceride, cholesteryl ester and protein. There are no widely available methods for direct measurement of LpX in routine laboratory practice. We present the heterogeneity of clinical and laboratory manifestations of the presence of LpX, a phenomenon which hinders LpX detection. The study was conducted on a 26-year-old female after liver transplantation (LTx) with severely elevated total cholesterol (TC) of 38 mmol/L and increased cholestatic liver enzymes. TC, free cholesterol (FC), cholesteryl esters (CE), triglycerides, phospholipids, HDL-C, LDL-C, and apolipoproteins AI and B were measured. TC/apoB and FC:CE ratios were calculated. Lipoprotein electrophoresis was performed using a commercially available kit and laboratory-prepared agarose gel. Commercially available electrophoresis failed to demonstrate the presence of LpX. Laboratory-prepared gel clearly revealed the presence of lipoproteins with γ mobility, characteristic of LpX. The TC/apoB ratio was elevated and the CE level was reduced, confirming the presence of LpX. Regular lipoprotein apheresis was applied as the method of choice in LpX disease and a bridge to reLTx due to chronic liver insufficiency. The detection of LpX is crucial as it may influence the method of treatment. As routinely available biochemical laboratory tests do not always indicate the presence of LpX, in severe hypercholesterolaemia with cholestasis, any discrepancy between electrophoresis and biochemical tests should raise suspicions of LpX disease.

Lipoprotein apheresis efficacy, challenges and outcomes: A descriptive analysis from the UK Lipoprotein Apheresis Registry, 1989–2017

Background and aimsIn 2008, the National Institute of Health and Care Excellence in the UK recommended that patients undergoing lipoprotein apheresis (LA) should be included in an anonymised registry. The UK Lipoprotein Apheresis Registry was subsequently established in 2011. MethodsBetween 2011 and 2017, data was entered retrospectively and prospectively by seven LA centres in the UK for 151 patients. Twenty-two patients were involved in a research study and were therefore excluded from the analysis. Observational data was analysed for the remaining 129 patients. ResultsMost patients had heterozygous familial hypercholesterolaemia (HeFH) (45.0%); 23.3% had homozygous FH (HoFH); 7.8% had hyper-lipoproteinaemia (a) (Lp(a)) and 24.0% had other forms of dyslipidaemia. Detailed treatment data is available for 63 patients relating to 348 years of LA treatment. The number of years of treatment per patient ranged from 1 to 15. The mean reduction in interval mean LDL-C from the pre-procedure baseline was 43.14%. The mean reduction in interval mean Lp(a) from baseline was 37.95%. The registry data also shows a 62.5% reduction in major adverse cardiovascular events (MACE) between the 2 years prior to, and the first 2 years following introduction of LA. ConclusionsThe data generated by the UK Lipoprotein Apheresis Registry demonstrates that LA is a very efficient method of reducing LDL-C and Lp(a) and lowers the incidence rate of MACE. LA is an important tool in the management of selected patients with HoFH and drug-resistant dyslipidaemias.

Implementation and 2‐year outcomes of the first FDA‐approved implantable apheresis vascular access device

Patients requiring chronic apheresis treatments typically lack sufficient peripheral venous access to support long-term therapy. Historically, central venous tunneled catheters, septum-bearing subcutaneous ports, and fistulas were used to obtain required blood flow rates for apheresis procedures. In 2017, the US Food and Drug Administration approved the first intravascular device specifically designed for apheresis therapy, the PowerFlow Implantable Apheresis IV Port. Several preimplementation meetings with key hospital stakeholders were held to determine the most efficient and safest strategy for integrating the PowerFlow device into our practice. Interventional radiologists implanted the apheresis port in patients meeting specified criteria. Performance metrics and adverse events were evaluated over a 2-year period, July 2017 through June 2019. Eighteen patients underwent apheresis therapy using the PowerFlow port. The most common apheresis therapy provided was extracorporeal photopheresis, followed by therapeutic plasma exchange and low-density lipoprotein apheresis. Flow rates up to 90 mL/min were obtained; the rates were limited by patient tolerance for the apheresis procedure. Complications included infection, obstruction due to fibroblastic sleeve, and migration of the vascular device. The estimated risk of PowerFlow-associated bloodstream infection in the study population was 0.18 per 1000 intravascular device days. The PowerFlow Implantable Apheresis IV Port can achieve flow rates necessary for all apheresis therapies and is a promising alternative vascular access device for patients undergoing apheresis.

Lipoprotein apheresis in Austria – Reduction of cardiovascular events by regular lipoprotein apheresis treatment

BackgroundIn Austria, about 12 patients per 1 million inhabitants are treated currently with lipoprotein (LP-) apheresis. In 2016 it has been suggested, that about 5000 patients were treated worldwide with LP-apheresis, more than half of them in Germany. Regular LP-apheresis aims to decrease apolipoprotein B-rich lipoproteins and to reduce cardiovascular events. In this analysis we present the current situation of LP-apheresis in Austria and we evaluated the cardiovascular event rate 2 years before versus 2 years after starting LP-apheresis. MethodsA retrospective analysis of 30 patients (19 men and 11 women) was performed at Athos Institute, Vienna, Austria. The study period included two years prior versus two years after the beginning of LP-apheresis. Cardiovascular events and interventions were defined as regarding the coronary (MACE) or the non-coronary (peripheral, cerebral or renal) vascular system. ResultsThe first cardiovascular event before treatment initiation occurred at a mean age of 48.4 years (range 34–73), treatment was started at a mean age of 55.6 years (range 34–73). The mean rate of incidence of cardiovascular events per patient per 2 years before beginning of LP-apheresis (y-2 and y-1) versus 2 years during treatment (y+1 and y+2) was reduced by 77.78% (1.50 versus 0.33 events/patient/2 years, p = 0.003). ConclusionsThe significant reduction in MACE and vascular disease during regular LP-apheresis at weekly intervals is consistent with data from the literature. Difficulties arise in comparing such studies due to different definition of events or interventions and different study durations. However, LP-apheresis is an efficient treatment option and causes significantly prolonged event-free survival for patients at risk.

Lipoprotein apheresis – Shortening of treatment intervals reduces cardiovascular events: Case reports

BackgroundLipoprotein (Lp-) apheresis is a life-long therapy, usually performed in weekly intervals. In some cases, however, atherosclerotic disease progresses despite adequate therapy with weekly Lp-apheresis and maximal lipid lowering medication. In an attempt to improve the effectiveness of therapy, we temporarily shortened treatment intervals of Lp-apheresis in patients with elevated lipoprotein(a) (Lp(a)) and further progression of coronary atherosclerosis despite weekly Lp-apheresis and maximal lipid lowering medication. MethodsWe illustrate three case reports of patients with elevated Lp(a), who underwent regular weekly Lp-apheresis treatment for secondary prevention. The intensified treatment protocol contained three therapies in two weeks (alternating 2 per week and 1 per week). ResultsThe shortening of treatment intervals achieved a stabilization of atherosclerotic disease in case 1. After a total of 68 therapies in 52 weeks (1.31 sessions/week) the elective coronary angiography revealed excellent long-term results. In case 2, the intensified treatment protocol is still ongoing. The patient reported a decrease in angina pectoris and an increase in exercise capacity since the beginning of more frequent therapy sessions. In some cases, as it is shown in case 3, a fast decision for shortening the treatment intervals is necessary. ConclusionsThe intensified treatment regimen resulted in an improvement in clinical symptoms and no further progression of atherosclerosis. In conclusion, shorter therapeutic Lp-apheresis intervals, at least temporarily, should be considered in patients who suffer from clinical and/or angiographic progression of atherosclerosis, despite maximal lipid lowering medication and weekly Lp-apheresis.

A complicated pregnancy in homozygous familial hypercholesterolaemia treated with lipoprotein apheresis: A case report

Background and aimsDuring pregnancy total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels increase significantly and lipoprotein apheresis (LA) is considered the most effective therapy in homozygous familial hypercholesterolaemia (HoFH) for modulating lipid and lipoprotein levels and reducing maternal and foetal complications. Clinical caseA primigravida 28 years old Caucasian female patient, previously diagnosed as to be HoFH, was admitted at our outpatient service at the beginning of pregnancy. MethodsThe patient was continuously submitted to LA every two weeks without foetal complication. During pregnancy two methods have been utilised: selective apheresis, and later plasma exchange. At 33 weeks gestational age the patient developed progressively hypertension, associated to LDL-C levels increase. Weekly LA was favoured. ResultsAt 34 weeks +5 days patient suddenly experienced acute chest pain and abnormal electrocardiogram heart tracing and cardiac enzymes increase.An emergency caesarean section was performed without complications and the foetus was healthy. The patient was immediately transferred to Coronary Intensive Care Unit, where she was diagnosed non-ST elevation myocardial infarction (NSTEMI). Notwithstanding the patient improved in few days and was quickly discharged in fair clinical condition. ConclusionsLA is a safe and effective tool in HoFH subjects even in pregnancy. Evidence based guidelines for the management of these patients during pregnancy are still lacking.

Microsomal triglyceride transfer protein inhibitor (lomitapide) efficacy in the treatment of patients with homozygous familial hypercholesterolaemia.

The aim of this study was to evaluate the effect of microsomal triglyceride transfer protein inhibitor (lomitapide) in patients with homozygous familial hypercholesterolaemia. In 12 homozygous familial hypercholesterolaemia patients treated with lipid-lowering drugs ± biweekly lipoprotein apheresis sessions (nine patients), daily lomitapide was added. The lipid profile (total cholesterol, low-density lipoprotein cholesterol, triglycerides, high-density lipoprotein cholesterol) before and after lomitapide treatment was evaluated. The follow-up period with lomitapide treatment was 3-24 months (13.8 ± 7.9). The median baseline low-density lipoprotein cholesterol level was 900 mg/dl (348-1070), after lipid-lowering drugs therapy was 383.5 mg/dl (214-866) and after lipid-lowering drugs + time-averaged level was 288 mg/dl (183.7-716.6). The addition of lomitapide lowered low-density lipoprotein cholesterol levels further by 56.8% compared to lipid-lowering drugs alone (mean reduction 262, 95% confidence interval (105.5-418.7), p = 0.005) and by 54% (mean reduction 182.9, 95% confidence interval (-342 - -23), p = 0.031) comparing to lipid-lowering drugs + lipoprotein apheresis (time-averaged level). The time-averaged level of low-density lipoprotein cholesterol in lipid-lowering drugs + lipoprotein apheresis patients compared with lipid-lowering drugs + lomitapide was 54% in favour of lomitapide (p = 0.031). Treatment with lomitapide in homozygous familial hypercholesterolaemia patients has a beneficial effect with a constant decrease of low-density lipoprotein cholesterol by 57% compared with classical lipid-lowering therapy and by 54% compared with classical lipid-lowering therapy and time-averaged level of low-density lipoprotein cholesterol.

Hefh In Real Life, How To: More Evolocumab Than Authorized

Background and Aims: Evolocumab represents a breakthrough in the treatment of hypercholesterolemia. The TAUSSIG study [NCT01624142] was conducted in subjects affected by Heterozygous Familial hypercholesterolemia (HeFH) already on chronic lipoprotein-apheresis (LA); evolocumab 420 mg was administered every 14 days at the end of each LA procedure, in addition to conventional medical therapy.