LDL apheresis is an extracorporeal elimination method that strives to specifically remove (if possible) LDL cholesterol (LDL-C) from the circulation. Currently, six effective methods are utilized for selective removal of LDL-C. Primary indications for LDL apheresis treatment include diagnoses of homozygous familial hypercholesterolemia and heterozygous familial hypercholesterolemia in patients that are refractory to, or intolerant of, standard therapy; as well as patients with an increase in Lp(a) that are refractory to, or intolerant of, pharmacotherapy. Thus far, however, no consensus has been reached concerning what LDL-C level represents the threshold for initiation of LDL apheresis, and opinions differ within individual countries. Although no large randomized studies have been conducted, a sufficient number of well-controlled studies do exist, and the significant effect of LDL apheresis on cardiovascular prognosis in severe hypercholesterolemia has been acknowledged worldwide.
Indications for LDL apheresis in FH
To date, few works on the issue of indications for LDL apheresis have been published worldwide. According to Thompson (2013), there are three main indications for treatment with LDL apheresis:
- Homozygous familial hypercholesterolemia (HFH)
- Heterozygous familial hypercholesterolemia that is refractory to, or the patient is intolerant of, standard treatment
- Patients with increased lipoprotein(a) that is refractory to, or the patient is intolerant of, high doses of nicotinic acid
At this time, however, there is no consensus on what LDL-C levels in FH represent the threshold for initiation of LDL apheresis, and opinions differ among individual countries (Table – Overview from 2013):
Table: Criteria for LDL apheresis
| Country | Criteria |
| USA | HoFH: LDL-C >12.9 mmol/L or |
| HeFH: LDL-C > 7.8 mmol/L or | |
| eFH: LDL-C > 5.2 mmol/L and presence of CAD | |
| All patients intolerant to standard pharmacotherapy or unresponsive to dietary measures, or for whom such measures have failed | |
| United Kingdom | HoFH: When hypolipidemic treatment reduced LDL-C < 50% or |
| LDL-C > 9 mmol/L | |
| patients with severe hypercholesterolemia, including HeFH with progressive CAD, when hypolipidemic treatment reduced LDL-C < 40% or LDL-C > 5 mmol/L or | |
| increased Lp(a) > 60 mg/dL with progressive LDL-C > 3.2 mmol/L during hypolipidemic treatment | |
| Germany | FH and LDL-C > 4.2 mmol/L during hypolipidemic and dietary treatment , and with a family history of CVD or |
| All patients with progressive CAD when LDL-C is > 3.1 mmol/L during hypolipidemic and dietary treatment or | |
| All patients with progressive CAD and Lp(a) > 60 mg/dL | |
| Australia | HoFH / HeFH: < 50% reduction in LDL-C even during maximum hypolipidemic and dietary treatment or |
| HoFH: LDL-C > 7 mmol/L during maximum hypolipidemic treatment or | |
| HeFH and presence of CAD when refractory to, or intolerant of hypolipidemic therapy, LDL-C > 5 mmol/L or | |
| Children with HoFH after 5 years of age, especially with LDL-C > 9 mmol/L during hypolipidemic treatment |
The criteria are strict in Germany. In accordance with the latest European Atherosclerosis Society consensus, target LDL-C values are < 2.5 mmol / L in FH patients, and 1.8 mmol / L in FH patients with manifestations of CAD and / or DM. There is no complete consensus regarding when to start LDL apheresis in children, especially homozygotes; but it is clear that it must be started early.
“Hard” data from evidence based medicine (e.g. large international randomized, prospective, blinded, placebo-controlled trials) with detailed assessments of the impact of LDL apheresis on cardiovascular (CV) risk in homozygous FH does not exist. That said, a sufficient number of well-controlled trials have been conducted and there is worldwide recognition regarding the impact of LDL apheresis on FH prognosis to the following extent:
- LDL apheresis success in homozygotes is indisputable; experts in the field agree there is no need for further studies in this direction.
- Experts likewise agree that LDL apheresis in heterozygous FH involving coronary arteries is undoubtedly beneficial.
- It is also likely to be beneficial in heterozygotes with progressing atheromatosis not involving coronary arteries, but some details must yet be resolved.
“Hard” data from evidence based medicine (e.g. large international randomized, prospective, blinded, placebo-controlled trials) with detailed assessments of the impact of LDL apheresis on cardiovascular (CV) risk in homozygous FH does not exist. That said, a sufficient number of well-controlled trials have been conducted and there is worldwide recognition regarding the impact of LDL apheresis on FH prognosis to the following extent:
- LDL apheresis success in homozygotes is indisputable; experts in the field agree there is no need for further studies in this direction.
- Experts likewise agree that LDL apheresis in heterozygous FH involving coronary arteries is undoubtedly beneficial.
- It is also likely to be beneficial in heterozygotes with progressing atheromatosis not involving coronary arteries, but some details must yet be resolved.