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2nd Congress of the European Group – International Society for Apheresis

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03/23/2018 - Pirouette | 8:30am - 10:00am 
iCal 
LP-apheresis in hyper-Lp(a) aemia

Chairs: Y. Endo (Otsu, Japan), tba

8:30am
IL-15
Actual situation of lipoprotein apheresis in patients with elevated lipoprotein(a)
*Ulrich Julius1
1 University Hospital at the Technische Universität Dresden, Department of Internal Medicine III, Dresden, Germany
Abstract text :

In Germany, the number of patients with elevated Lipoprotein(a) (Lp(a)) levels who newly started lipoprotein apheresis (LA) was steadily increasing in the last years. The official as well as own data will be shown. But the definition of an isolated Lp(a) hyperlipidemia is still quite unclear with respect to LDL cholesterol (LDL-C) levels. Several patients have an elevation of both parameters despite being treated with lipid-lowering drugs. The Federal Joint Committee required that a progress of atherosclerosis has been documented as a part of the indication for LA. The definition of such a progress is still under discussion. The age of a given patient, the severity of the cardiovascular event and the family history should also be taken into consideration. Usually, all vascular territories should be investigated. Should a Cardio-CT be performed in these high-risk patients?
We and others had published that the effect of LA therapy on the incidence of cardiovascular events is much higher in patients with elevated Lp(a) levels when compared with patients with hypercholesterolemia and normal Lp(a) concentrations. The high efficiency of LA in patients with elevated Lp(a) levels has been confirmed in the Jaeger and the Pro(a)Life studies where patients at our Center took part.
Most available LA methods acutely decrease both LDL-C and Lp(a). Thus it appears to be difficult to differentiate these effects on outcome data. Unfortunately, no outcome data are available comparing different LA methods.
The usually recommended interval between LA sessions is one week. But in some patients the Lp(a) levels rebound more quickly – in such patients two sessions per week should be performed. Examples of patients with this therapeutic approach will be discussed. Up to now no target value for Lp(a) has been defined.
An open question is the indication for LA in patients with highly elevated Lp(a) who suffered from one or multiple strokes and show only slight or no atherosclerotic lesions at the carotids.
In studies PCSK9 inhibitors reduced Lp(a) level by about 25 – 30 %. Real world data show that such a reduction is only rarely seen in patients with extremely elevated Lp(a) concentrations. Own experience will be reported.
In the future, an antisense oligonucleotide against apolipoprotein(a) will be a new therapeutic option to effectively decrease Lp(a) concentrations. But most probably outcome data will be required before this option will be an essential part of the daily medical practice.



9:00am
IL-16
Lipoprotein(a) – Marker and Target for Lipoprotein Apheresis
*Reinhard Klingel1
1 Apheresis Research Institute, , Cologne, Germany
Abstract text :

Lipoprotein(a) (Lp(a)) is composed of an LDL-like particle in which apoB is covalently bound to apolipoprotein(a) (apo[a]). Lp(a) is an independent cardiovascular (CV) risk factor playing a causal role for atherosclerotic cardiovascular disease (CVD) and calcific aortic valve stenosis. Recent studies have suggested that elevated Lp(a) remains a risk factor even in patients who achieve LDL-C <70mg/dl. Within populations, there is extensive apo(a) size heterogeneity, with >40 different isoforms. Within individuals, >80% carry 2 different-sized apo(a) isoforms. Data showed an inflection for risk of myocardial infarction at Lp(a) >30mg/dl. Genome-wide association studies and Mendelian randomization studies were also consistent with these estimates. Lp(a) levels are generally expressed as mg/dl of the mass of the entire particle, which includes the protein content of apoB-100 and apo(a), and their associated lipids (cholesterol, cholesteryl esters, phospholipids, and triglycerides), as well as carbohydrates attached to apo(a), or in nmol/l as a particle number of apo(a). Lp(a) mass assays have an inherent limitation due to the heterogeneity of Lp(a) particle sizes, making it difficult to standardize assays with appropriate calibrators. Unlike normally distributed LDL-C, Lp(a) levels are skewed leftward, and most individuals (~70%) have values in the normal range of <30 mg/dl.


Lipoprotein apheresis (LA) is a safe well tolerated outpatient treatment to lower LDL-C and Lp(a) by 60%-70%, and is the ultimate therapeutic option in patients with hyperlipoproteinemias (HLP) involving LDL particles. Major therapeutic effect of LA is preventing CV events. Lp(a)-HLP associated with progressive CVD despite effective treatment of all other CV risk factors in particular LDL-C has been approved as indication for LA in Germany since 2008.


The Pro(a)LiFe-study investigated with a prospective multicenter design the long-term preventive effect of LA on incidence rates of CV events over a period of 5 years in 170 consecutive patients with a mean Lp(a) concentration of 108mg/dl and progressive CVD after in median 2 CV events had occurred (Roeseler, 2016). 154 patients (90.6%) completed 5 years follow-up. Significant decline of the mean annual major adverse cardiac event (MACE) rate was observed comparing two years prior to LA to 5 years with regular LA (p<0.0001). Although in most patients small isoforms accounted for the high Lp(a) level, in 4.7% of patients large isoforms were solely responsible for the elevated Lp(a), but patients were clinically indistinguishable. Calculation of isoform specific concentrations allowed to confirm the equivalence of 60 mg/dl or 120 nmol/l as Lp(a) thresholds of the German LA guideline.


Ref.: Roeseler for the Pro(a)LiFe-study group. Arterioscler Thromb Vasc Biol 2016; 36: 2019-2027.


 



9:30am
IL-17
Treating Lipoprotein(a)-hyperproteinemia and Progressive Cardiovascular Disease with Lipid-Apheresis in North America
*Patrick Moriarty1, Heather Minchew1, Donald Okonta1, Lauryn Denney1
1 University of Kansas Medical Center, Clinical Pharmacology, Kansas City, United States
Abstract text :

Background: Lipoprotein(a) [Lp(a)] is an independent cardiovascular risk factor, found in more than 20% of the world"s population, but presently no appropriate pharmacotherapy exists for lowering Lp(a). In Germany, lipid-apheresis (LA) therapy, acutely lowers Lp(a) >60%, is approved for Lp(a)- hyperproteinemia and progressive cardiovascular disease (CVD) irrespective of LDL-C levels. In North America, LA treatment for Lp(a) is approved for patients if their LDL-C level is >160mg/dL.


Methods: Examine a single site"s experience using biweekly LA therapy for the reduction of cardiovascular events in CVD patients who received LA therapy for more than 6 months with an Lp(a) >50mg/dL and LDL-C <160mg/dL.


Results: A total of 15 CVD patients (9 male), ages 56±16 (range 13-82), qualified with a mean Lp(a) level of 123.28 mg/dL and LDL-C level of 100.14 mg/dL. The mean period of LA treatment was 3.54 years (range 8 months-7.5 years). Mean pre-apheresis cardiovascular events and interventions occurred 4.28 years (range 1-11.5 years) before initiation of LA therapy. Since beginning LA therapy only 2 patients experienced a cardiovascular event consisting of stent placement (6 months and 3 years post-LA) for angina symptoms.


Conclusion:  Lp(a) is an independent CVD risk factor and LA is currently the only therapy available to successfully treat Lp(a). Until future treatments become available LA therapy should be considered for Lp(a)-hyperproteinemia patients with progressive CVD, on maximum lipid modifying pharmacotherapy, irrespective of their LDL-C levels.


 




































LA Patients (n=15)



CVD Risk Factors


     Family History of CVD


     Hypertension


     Diabetes



 


10


9


4


 


8


6


11


4



Lipid Lowering Therapies


     Statin


     Ezetimibe


     Fish oil


     PCKS9 inhibitor



 



Pre-LA Therapy



Post-LA Therapy



Lab Levels


     Lp(a) (mg/dL)



 


123.28±4.26



 


44.63±3.77 (-63.8%)



     LDL (mg/dL)



100.14±6.41



29.42±3.08 (-70.63%)



Cardiovascular event


     Stroke    


     Myocardial infarction


          CABG


          Stent



 


5 (2.8 years pre-LA)


10 (5.7 years pre-LA)


8 (3.5 years pre-LA)


9 (5.11 years pre-LA)



 


0


0


0


2 (1.79 years post-LA)



 


Pre-LA is defined as the time period before LA therapy was initiated, post-LA is defined at the time period that patients received LA therapy.