LDL - lowering apheresis in FH

• NICE suggest that a clinician should consider offering LDL apheresis for the treatment of adults and children/young people with homozygous FH (1)
  • timing of initiation of LDL apheresis should depend on factors such as the person's response to lipid-modifying drug therapy and presence of coronary heart disease
  • in exceptional instances (such as when there is progressive, symptomatic coronary heart disease, despite maximal tolerated lipid-modifying drug therapy and optimal medical and surgical therapy), healthcare professionals should consider offering LDL apheresis for the treatment of people with heterozygous FH. This should take place in a specialist centre on a case-by-case basis and data recorded in an appropriate registry
  • NICE recommend arterio-venous fistulae as the preferred method of access for people with FH who are offered treatment with LDL apheresis. People should be counselled about possible benefits and complications of this procedure
  • routine monitoring of the person's iron status should be carried out and iron supplementation initiated as required for people with FH who are receiving treatment with LDL apheresis
  • angiotensin-converting enzyme (ACE) inhibitors should not be used in people with FH who are being treated with LDL apheresis. Instead, ACE inhibitors should be substituted with angiotensin-receptor blocking agents
  • people with FH who are receiving blood pressure-lowering drug therapy should have this reviewed and considered for discontinuation on the morning of the day of LDL apheresis
  • people with FH who are taking warfarin should have this discontinued approximately 4 days before LDL apheresis and substituted with low molecular weight heparin
  • people with FH who are receiving anti-platelet therapy should have this continued if they are receiving treatment with LDL apheresis

Categories of patients eligible for LDL apheresis

Three categories of patients considered eligible had earlier been identified by the HEART-UK Working Group on LDL apheresis (2):

• (i) children and adults with homozygous FH whose serum total cholesterol remained >9 mmol/l or decreased by <50% on drug therapy;
• (ii) FH heterozygotes with progressive coronary artery disease (CAD) whose LDL cholesterol remained >5 mmol/l or decreased by <40% on maximal drug therapy or exceptionally, cases with lower levels of LDL;
• (iii) patients with lipoprotein (a) (Lp(a)) >60 mg/dl and progressive CAD whose LDL cholesterol remained >3.2 mmol/l despite drug therapy

Target levels of cholesterol during long-term apheresis in FH homozygotes

• it is proposed that target levels for FH homozygotes undergoing repetitive apheresis should be as follows (3):
  • (i) An acute reduction in total cholesterol of >= 65% or in LDL cholesterol of >=70% on average during each procedure
  • (ii) An interval mean total cholesterol of <7 mmol/l or LDL cholesterol <6.5 mmol/l (or decreases of >60% or >65%, respectively from baseline values off all treatment)
  • (iii) A baseline level of total cholesterol of <9mmol/l or LDL cholesterol <8.5 mmol/l (or decreases of >50% or >55%, respectively from baseline values off all treatment)
• frequency of apheresis treatment:
  • achieving these reductions will usually necessitate treating 1.5-2 plasma or blood volumes at 2-weekly intervals. However, sometimes it may be preferable to treat smaller volumes more frequently. Apheresis should be embarked upon as early as feasible, ideally not later than 7 years of age, which will usually necessitate the creation of an arterio-venous fistula. Whenever possible, apheresis should be combined with maximum tolerated doses of atorvastatin or rosuvastatin plus ezetimibe 10mg daily (3)

Evidence for use of apheresis:

• a UK lipoprotein apheresis registry was analysed and revealed (4):
  • 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
  • the study authors concluded 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"

Reference:

• (1) NICE (August 2008). Identification and management of familial hypercholesterolaemia
• (2) Thompson GR, Barbir M, Davies D, et al. Recommendations for the use of LDL apheresis. Atherosclerosis 2008;198:247-55.
• (3) Thompson GR et al. Efficacy criteria and cholesterol targets for LDL apheresis. Atherosclerosis. 2010 Feb;208(2):317-21.
• (4) Pottle A., Thompson, G., Barbir, B., Bayly, G., Cegla, J., Cramb, R., Dawson, T et al. Lipoprotein apheresis efficacy, challenges and outcomes: a descriptive analysis from the UK Lipoprotein Apheresis Registry. 1989-2017.  Atherosclerosis 2019: 290. 44-51