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Apheresis and Lp(a)
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Apheresis as novel treatment for refractory angina with raised lipoprotein(a): a randomized controlled cross-over trial

2017 Apr 26. doi: 10.1093/eurheartj/ehx178. [Epub ahead of print



To determine the clinical impact of lipoprotein apheresis in patients with refractory angina and raised lipoprotein(a) > 500 mg/L on the primary end point of quantitative myocardial perfusion, as well as secondary end points including atheroma burden, exercise capacity, symptoms, and quality of life.


We conducted a single-blinded randomized controlled trial in 20 patients with refractory angina and raised lipoprotein(a) > 500 mg/L, with 3 months of blinded weekly lipoprotein apheresis or sham, followed by crossover. The primary endpoint was change in quantitative myocardial perfusion reserve (MPR) assessed by cardiovascular magnetic resonance. Secondary endpoints included measures of atheroma burden, exercise capacity, symptoms and quality of life.


The primary endpoint, namely MPR, increased following apheresis (0.47; 95% CI 0.31-0.63) compared with sham (-0.16; 95% CI - 0.33-0.02) yielding a net treatment increase of 0.63 (95% CI 0.37-0.89; P < 0.001 between groups). Improvements with apheresis compared with sham also occurred in atherosclerotic burden as assessed by total carotid wall volume (P < 0.001), exercise capacity by the 6 min walk test (P = 0.001), 4 of 5 domains of the Seattle angina questionnaire (all P < 0.02) and quality of life physical component summary by the short form 36 survey (P = 0.001).


Lipoprotein apheresis may represent an effective novel treatment for patients with refractory angina and raised lipoprotein(a) improving myocardial perfusion, atheroma burden, exercise capacity and symptoms.


The effect of apheresis on Lipoprotein(a) - Journal of Clinical Apheresis Guidelines and Clinical Studies.


Lipoprotein apheresis: present and future uses 

Since 2010, the German healthcare ministry has approved lipoprotein apheresis therapy for patients with an elevated lipoprotein(a) and ongoing cardiovascular disease irrespective of LDL-C levels.


Guidelines on the Use of Therapeutic Apheresis inClinical Practice—Evidence-Based Approach from theWriting Committee of the American Society for Apheresis: The Sixth Special Issue

Joseph Schwartz, Jeffrey L. Winters, Anand Padmanabhan, Rasheed A. Balogun, Meghan Delaney, Michael L. Linenberger, Zbigniew M. Szczepiorkowski, Mark E. Williams, Yanyun Wu, and Beth H. Shaz

The American Society for Apheresis (ASFA) JCA Special Issue Writing Committee is charged with reviewing,updating and categorizing indications for therapeutic apheresis. Beginning with the 2007 ASFA Special Issue(Fourth Edition), the committee has incorporated systematic review and evidence-based approach in the grading and categorization of indications. This Sixth Edition of the ASFA Special Issue has further improved the process of using evidence-based medicine in the recommendations by consistently applying the category and GRADE system definitions, but eliminating the "level of evidence” criteria (from the University HealthCare Consortium) utilized in prior editions given redundancy between GRADE and University HealthCare Consortium systems. The general layout and concept of a fact sheet that was utilized in the Fourth and Fifth Editions, has been largely maintained in this edition. Each fact sheet succinctly summarizes the evidence for the use of therapeutic apheresis in a specific disease entity. This article consists of 78 fact sheets (increased from 2010) for therapeutic indications in ASFA categories I through IV, with many diseases categorized having multiple clinical presentations/situations which are individually graded and categorized. J. Clin. Apheresis 28:145–284, 2013.


Lipoprotein Apheresis in Patients with Maximally Tolerated Lipid Lowering Therapy, Lp(a)-Hyperlipoproteinemia and Progressive Cardiovascular Disease: Prospective Observational Multicenter Study

Josef Leebmann; Eberhard Roseler; Ulrich Julius; Franz Heigl; Ralf Spitthoever; Dennis Heutling; Paul Breitenberger; Winfried Maerz; Walter Lehmacher; Andreas Heibges; Reinhard Klingel; for the Pro(a)LiFe*-Study Group

Conclusions—In patients with Lp(a)-HLP, progressive CVD and maximally tolerated lipid lowering medication LA effectively lowered the incidence rate of cardiovascular events.


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.

 Heigl F1, Hettich R2, Lotz N2, Reeg H2, Pflederer T2, Osterkorn D3, Osterkorn K3, Klingel R4.

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%.


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