Lipoprotein Apheresis

Gilbert Thompson Imperial College

Hammersmith Hospital London

Rationale for lipoprotein apheresis

• To prevent the development, arrest progression or

induce regression of atherosclerosis by long-term

lowering of plasma levels of cholesterol-rich lipoproteins

in hyperlipidaemic subjects refractory to drug therapy.

LDL particle

22 nm

Lipoprotein apheresis methods

Unselective removal from plasma • Plasma exchange

Selective removal from plasma • Differential filtration • Adsorption • Precipitation

Selective removal from blood • Adsorption

Double filtration system (L.I.N.C.)

Dextran sulphate adsorption (Kaneka)

Plasma Whole blood

Direct Adsorption of Lipoproteins (DALI) system (Fresenius)

Heparin Extracorporeal LDL Precipitation (HELP) system (Braun)

Parameters of lipoprotein apheresis

HEART UK indications for lipoprotein apheresis (Atherosclerosis 2008;198:247-55)

• Homozygous Familial Hypercholesterolaemia (FH) • Heterozygous FH with progressive CAD refractory to statins • Patients with Lp(a) > 600 mg/l and progressive CAD despite

maximal drug therapy

Homozygous familial hypercholesterolaemia

• Planar xanthomas in early childhood

• Atheroma of aortic root before puberty

• Serum cholesterol 15 -30 mmol/l from birth

• Sudden death in adolescence or early adulthood

Apheresing homozygote, aged 6 (1989)

Serum cholesterol before and during 8 yrs of lipoprotein apheresis in homozygous FH child

Tendon xanthoma before & after 6 years of apheresis

Cumulative impact of apheresis & drug therapy in homozygous FH

0

5

10

15

20

25

LDL-C mmol/l

Untreated Apheresis Apheresis + Atorvastatin 80 mg

Apheresis + Atorvastatin 80 mg + Ezetimibe 10 mg

-70% - 45%

- 17%

- 8%

Efficacy of lomitapide in FH homozygotes (n=29) (Cuchel et al, 2012)

Lipoprotein apheresis in an FH heterozygote

Frequency of coronary angiographic change in FH trials of ≥ 2 years duration

0

50

100

Controls Drugs Aph + Drugs

Regression

No change

Progression

n = 89 n = 150 n = 114

Perc

ent o

f Pat

ient

s

Fibrosed lesion after 6½ years of apheresis

Cholesterol-rich coronary atheromatous plaque

Lipoprotein (a)

Effects of weekly apheresis on Lp(a) levels and major adverse coronary events (MACE) (Jaeger et al, 2009)

Reduction in MACE rate similar whether LDL-C < 2.6 or > 2.6 mmol/l

Lipoprotein apheresis in 3 lipid centres in the UK: Cardiff, Hammersmith & Harefield

(March, 2013)

Category Number/Frequency

Patients 48

Procedures 105/month

Homozygous FH 23%

Heterozygous FH (statin-refractory) 73%

HyperLp(a)aemia 4%

Longest duration 23 years

NHSBT Specialist Therapeutic Services (STS)

• STS centres in England : North-West (Manchester & Liverpool) Sheffield Leeds Bristol Oxford

• STS performed 3,800 procedures in 2011-2012 Lipoprotein apheresis 4% (≈ 13/ month)

Hypertriglyceridaemic acute pancreatitis

Serum triglycerides > 10 mmol/l AND

clinical evidence of incipient acute pancreatitis

Summary

• Lipoprotein apheresis involves the extracorporeal removal of low density lipoprotein and lipoprotein (a) particles from whole blood or plasma by adsorption, precipitation or differential filtration.

• Used weekly on a long term basis it provides safe and effective treatment of patients at high risk of premature cardiovascular disease (CVD) from inherited increases in those atherogenic lipoproteins.

• The procedure is first-line therapy for homozygous familial hypercholesterolaemia (FH) and is increasingly used to treat patients with CVD due to statin-refractory heterozygous FH or raised levels of lipoprotein (a).

• Lipoprotein apheresis or plasma exchange may also be used to prevent acute pancreatitis in patients with severe hyper-triglyceridaemia.