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Review
. 2022 Dec 1;33(6):326-335.
doi: 10.1097/MOL.0000000000000853. Epub 2022 Oct 4.

New algorithms for treating homozygous familial hypercholesterolemia

Tycho R Tromp  1 , Marina Cuchel  2
Affiliations
Review

New algorithms for treating homozygous familial hypercholesterolemia

Tycho R Tromp et al. Curr Opin Lipidol. .

Abstract

Purpose of review: We reviewed current and future therapeutic options for patients with homozygous familial hypercholesterolemia (HoFH) and place this evidence in context of an adaptable treatment algorithm.

Recent findings: Lowering LDL-C levels to normal in patients with HoFH is challenging, but a combination of multiple lipid-lowering therapies (LLT) is key. Patients with (near) absence of LDL receptor expression are most severely affected and frequently require regular lipoprotein apheresis on top of combined pharmacologic LLT. Therapies acting independently of the LDL receptor pathway, such as lomitapide and evinacumab, are considered game changers for many patients with HoFH, and may reduce the need for lipoprotein apheresis in future. Liver transplantation is to be considered a treatment option of last resort. Headway is being made in gene therapy strategies, either aiming to permanently replace or knock out key lipid-related genes, with first translational steps into humans being made. Cardiovascular disease risk management beyond LDL-C, such as residual Lp(a) or inflammatory risk, should be evaluated and addressed accordingly in HoFH.

Summary: Hypercholesterolemia is notoriously difficult to control in most patients with HoFH, but multi-LLT, including newer drugs, allows reduction of LDL-C to levels unimaginable until a few years ago. Cost and availability of these new therapies are important future challenges to be addressed.

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Conflict of interest statement

T.R.T. declares no conflicts of interest. M.C. reports institutional support for the conduction of clinical trials from Regeneron Pharmaceuticals and Regenxbio; consulting fees from Amryt Pharma.

Figures

FIGURE 1
FIGURE 1
Combination lipid-lowering therapy in treating HoFH. Reprinted with permission from [▪▪].
FIGURE 2
FIGURE 2
Treatment algorithm for HoFH. ∗Depending on cost, availability and patient's residual LDLR activity. ANGPTL3i, angiopoietin-like protein 3 inhibition; CETP, cholesterol ester transfer protein; CVD, cardiovascular disease; HoFH, homozygous familial hypercholesterolemia; k/o, knockout; LDL-C, LDL cholesterol; LDLR, LDL receptor; LLT, lipid lowering therapy; Lp(a), lipoprotein(a); PCSK9i, proprotein convertase subtilisin/kexin type 9 inhibition.
Box 1
Box 1
no caption available
See this image and copyright information in PMC

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