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Harangi et al. LDL apheresis or PCSK9 inhibition, or both?

arcus. This allows for risk assessment and diagnosis FH and coronary artery disease. Furthermore,
[10]
when genetic testing is not available. Criteria that are findings from the ODYSSEY ESCAPE study suggest
most commonly used in the diagnosis of FH is the a role for alirocumab in the overall management of
Dutch Lipid Network criteria. Genetic testing is critical patients with heterozygous FH undergoing regular
[3]
for cascade screening and genetic counseling. [1] lipoprotein apheresis therapy, with the potential to
avoid apheresis treatments or delay the requirement
Total cholesterol levels of 350-550 mg/dL (9- for such treatments. [11]
14.2 mmol/L) are typical of heterozygous FH while
total cholesterol levels of 650-1,000 mg/dL (16.8- Here we demonstrate the efficacy of selective LDL
25.9 mmol/L) are typical of homozygous FH. In apheresis, PCSK9 inhibitor evolocumab and the
[4]
heterozygous patients LDL-C levels are usually > combination of the two treatment strategies in the case
190 mg/dL (> 4.9 mmol/L). In adults with homozygous of a severe heterozygous FH patient.
FH, untreated LDL-C levels are generally, but not
always, > 500 mg/dL (> 13 mmol/L). However, levels CASE REPORT
can be lower in children or in treated individuals. Thus,
LDL-C levels are not sufficient to confirm a diagnosis. [5] The 48-year-old female patient (body weight:
85 kg, height: 176 cm, body mass index: 27.4 kg/m )
2
FH is associated with high risk of enhanced with extremely high total cholesterol, LDL-C and
atherogenesis leading to the early development lipoprotein(a) [Lp(a)] levels was treated by our Lipid
of coronary artery disease (CAD), carotid artery ambulance. She had xanthelasmas on both eye lids
disease and peripheral artery disease. The European [Figure 1], but neither xanthoma nor corneal arcus
Atherosclerosis Society suggests LDL-C goals of less could be seen.
than 100 mg/dL (2.59 mmol/L) in all adults with FH, and
less than 70 mg/dL (1.81 mmol/L) in adults with known Carotid artery ultrasound proved significant stenosis
CAD or diabetes mellitus. Therefore, there is an on both sides. Electrocardiography, echocardiography
[3]
ardent need for an aggressive therapeutic intervention and exercise electrocardiography did not show the
based on high dose statin or statin and ezetimibe signs of CAD. Using the Dutch Lipid Network Criteria
administration, selective LDL-apheresis or newly the diagnosis of FH is “probable”. Sequencing of the
developed further therapeutic strategies including the LDL receptor gene we found a known pathogenic
inhibition of PCSK9. [6]
mutation in heterozygous form (c.1865 A>G, exon
LDL apheresis techniques are artificial extracorporeal 13). Since the hypercholesterolemia, we found is
unexpectedly severe in heterozygous FH, further
methods for LDL-C elimination. There are various genetic tests are in process. Although mildly
methods, including cascade filtration or lipid filtration,
immunoadsorption, heparin-induced LDL precipitation, elevated triglyceride (3.1 mmol/L) and lower HDL-C
dextran sulfate LDL adsorption, and the LDL (1.1 mmol/L) levels are not usual in FH, the fact that
hemoperfusion. All of these techniques are effective the patient was overweight may explain this.
and well tolerated. The constant reduction of cholesterol Despite the maximum dose of combined treatment
is meant, above all, to prevent the progression or the
development of atherosclerosis. [7] (rosuvastatin 40 mg/day, ezetimibe 10 mg/day,
fenofibrate 267 mg/day), lipid levels were continuously
Human monoclonal antibodies against PCSK9: high above the goals (total cholesterol 11.7 mmol/L,
alirocumab and evolocumab have recently been LDL-C 9.1 mmol/L). Therefore, we indicated the
approved by the Food and Drug Administration. selective LDL apheresis treatment once a month
These agents target and inactivate PCSK9, a hepatic (financially supported by the Hungarian National
protease that attaches and internalizes LDL receptors Health Insurance Company). We performed the
into lysosomes hence promoting their destruction.
[8]
By preventing LDL receptor destruction, LDL-C levels
can be lowered 50-60% above that achieved by statin
therapy alone. Although the data are deficient,
[9]
PCSK9 inhibitors may reduce the frequency or even
eliminate the need for LDL apheresis therapy. A recent
study reported that switching from LDL apheresis to
evolocumab maintained the LDL-lowering effect but
did not decrease high-density lipoprotein cholesterol Figure 1: Xanthelasma on both eye lids of the patient with
(HDL-C) levels in three patients with heterozygous heterozygous familial hypercholesterolemia
92 Vessel Plus ¦ Volume 1 ¦ June 27, 2017