Defining the Role of Lipoprotein Apheresis in the Management of Familial Hypercholesterolemia

Abstract

Familial hypercholesterolemia (FH) is an autosomal co-dominant disorder characterized by a marked elevation of serum low-density lipoprotein (LDL) cholesterol (LDL-C) concentration, which in turn is associated with a greatly increased risk of premature cardiovascular disease. International consensus recommends the use of statins as the first line of treatment for patients with this condition. However, homozygote FH patients with persistently elevated LDL-C levels are usually resistant to multiple-drug therapy. Fortunately, LDL apheresis (or simply 'lipoprotein apheresis') provides a treatment option for patients who are refractory or intolerant to lipid-lowering medications, or if there is progressive cardiovascular disease despite maximal drug therapy. Lipoprotein apheresis is an extracorporeal LDL-C-lowering treatment similar in concept to renal dialysis. There are now five main methods for extracorporeal lipoprotein apheresis in use, namely dextran sulfate adsorption (DSA), heparin extracorporeal LDL precipitation (HELP), polyacrylate full blood adsorption (PFBA or DALI® system) using hemoperfusion, immunoadsorption, and filtration plasmapheresis. Lipoprotein apheresis has been shown to be successful in reducing LDL-C levels, as well as levels of lipoprotein(a) [Lp(a)], a prothrombotic proatherogenic lipoprotein. In contrast, however, lipoprotein apheresis seems to have a smaller effect in preventing atherosclerosis progression, thus suggesting that a major component of the reduction in cardiovascular events may be mediated by mitigating Lp(a) levels. Side effects are infrequent and mild, and have mainly consisted of lightheadedness, nausea, vomiting, and hypotension. As these are often bradykinin-mediated and associated with concomitant ACE inhibitor use, angiotensin type 2 receptor antagonists should be used instead of ACE inhibitors with DALI and PFBA. Nevertheless, there is scope for wider application of lipoprotein apheresis. The high cost and invasive nature of lipoprotein apheresis limits uptake; however, it is an important treatment modality that should be considered in carefully selected patients. National and international registries compiling outcome data for lipoprotein apheresis need to be established to help expand the evidence base regarding its effectiveness.

Validation of a new method for non-invasive assessment of vasomotor function

“…LA treatment was undertaken using three systems according to patient tolerability and clinical requirements, polyacrylate whole blood adsorption (n ¼ 8), whole blood dextran sulphate adsorption (n ¼ 1), or plasma dextran sulphate adsorption (n ¼ 3), as previously described. 6 FMD was not assessed concomitantly in study 3 due to time, equipment and space limitations.…”

The incidence of cardiovascular events is largely reduced in patients with maximally tolerated drug therapy and lipoprotein apheresis. A single-center experience

“…Drawbacks of LA include limited availability, procedure duration and permanent vascular access [11,13]. Despite those limitations, a marked improvement in the patients' health is evidenced by the significant ACVE reduction and consequent lower health care expenses to treat new events [6].…”

“…According to the patients characteristics (biocompatibility for LA systems, concomitant ACE inhibitors/ARBs therapy, etc.) [11] two different LA systems were used: dextran-sulfate absorption from plasma (Liposorber Ò -LA systems; Kaneka, Osaka, Japan) in 18/30 (60%) patients and heparin-induced LDL precipitation apheresis (HELP Ò , Plasmat Futura Ò ; B. Braun, Melsungen, Germany) in 12/30 (40%) [12].…”

Lipoprotein-apheresis reduces circulating microparticles in individuals with familial hypercholesterolemia

“…For clinical reasons patients underwent treatment using three different techniques: polyacrylate whole blood adsorption (DALI® n = 8), whole blood dextran sulfate adsorption (n = 1), or plasma dextran sulfate adsorption (n = 3), as described previously (24). Patients attended the Lipid Unit at University Hospital Llandough, Cardiff for apheresis treatment as part of their normal clinical care.…”