Current management of severe homozygous hypercholesterolaemias

Naoumova, R.P.; Thompson, Gilbert R.; Soutar, Anne K.

doi:10.1097/01.mol.0000137222.23784.2a

Cited by 88 publications

(52 citation statements)

References 93 publications

(77 reference statements)

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“…[92][93][94] These high plasma LDL-C levels lead to deposits of cholesterol in tendons, cutaneous tissues, and vasculature, including the coronary arteries, aortic root and valve, carotid arteries, and renal arteries. 95 Severe and widespread atherosclerosis occurs in all major arterial beds from a young age. 92,94 Untreated patients with homozygous FH who are LDL receptor negative (<2% residual of normal LDL receptor activity) rarely survive beyond the second decade.…”

Section: Natural History Of Homozygous Fh and Subclinical Atherosclermentioning

confidence: 99%

The Agenda for Familial Hypercholesterolemia

Gidding¹,

Champagne²,

Ferranti³

et al. 2015

Circulation

588

353

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Section: Natural History Of Homozygous Fh and Subclinical Atherosclermentioning

confidence: 99%

The Agenda for Familial Hypercholesterolemia

Gidding¹,

Champagne²,

Ferranti³

et al. 2015

Circulation

588

353

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“…In the third pregnancy trimester, especially on delivery, high-intensity stress is added to the cardiovascular system; therefore, LDL apheresis should be performed during pregnancy. Several studies have reported that LDL apheresis therapy could be safely conducted during pregnancy, leading to delivery 72,84,85) . During lactation, lipid-lowering agents other than bile acid resins should also be discontinued, and periodic LDL apheresis therapy must be continued for LDL-C control.…”

Section: Drug Therapy For Homozygous Fhmentioning

confidence: 99%

Guidelines for the Management of Familial Hypercholesterolemia

Harada‐Shiba

Arai

Oikawa

et al. 2012

JAT

167

164

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Familial hypercholesterolemia (FH) is a highly prevalent autosomal dominant hereditary disease, generally characterized by three major signs, hyper-low-density-lipoprotein (LDL) cholesterolemia, tendon/skin xanthomas and premature coronary artery disease (CAD). Because the risk of CAD is very high in these patients, they should be identified at an early stage of their lives and started on intensive treatment to control LDL-cholesterol. We here introduce a new guideline for the management of FH patients in Japan intending to achieve better control to prevent CAD. Diagnostic criteria for heterozygous FH are 2 or more of 1) LDL-cholesterol ≥ 180 mg/dL, 2) tendon/skin xanthoma(s), and 3) family history of FH or premature CAD within second degree relatives, for adults; and to have both 1) LDL-cholesterol ≥ 140 mg/dL and 2) family history of FH or premature CAD within second degree relatives, for children. For the treatment of adult heterozygous FH, intensive lipid control with statins and other drugs is necessary. Other risks of CAD, such as smoking, diabetes mellitus, hypertension etc., should also be controlled strictly. Atherosclerosis in coronary, carotid, or peripheral arteries, the aorta and aortic valve should be screened periodically. FH in children, pregnant women, and women who wish to bear a child should be referred to specialists. For homozygotes and severe heterozygotes resistant to drug therapies, LDL apheresis should be performed. The treatment cost of homozygous FH is authorized to be covered under the program of Research on Measures against Intractable Diseases by the Japanese Ministry of Health, Labour, and Welfare.

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“…Individuals with FH are at increased risk for cardiac events such as premature myocardial infarction and early death from premature coronary heart disease (CHD) especially in patients with severe forms of the disease if left untreated. 2,9,10 HeFH is characterized by 1 normally functioning gene and is less severe and more responsive to treatment such as statins than HoFH. The mean age for the onset of CVD in men with HeFH is 42 to 46 years and in women, onset is 51 to 52 years.…”

mentioning

confidence: 99%

“…11,12 HoFH is a severe, aggressive form of FH, which is often unresponsive to traditional treatment for hypercholesterolemia owing to the patient's lack of functional LDL receptors. 10,12 In patients with HoFH, the mean age at the time of diagnosis of CVD is 20 years. 3,[35][36][37] Risk stratification algorithms are often used to identify candidates for drug therapy on the basis of estimated CVD risk.…”

mentioning

confidence: 99%

Management of Familial Hypercholesterolemia: A Review of the Recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia

Robinson

2013

JMCP

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suMMaRyFamilial hypercholesterolemia (FH) is a genetic disorder of lipid metabolism that is characterized by a significant elevation in levels of low-density lipoprotein cholesterol (LDL-C), and patients are at very high risk for premature coronary heart disease (CHD). The etiology of FH includes known mutations in the gene of the LDL receptor, LDLR ; the gene of apolipoprotein B, apo B ; and the proprotein convertase subtilisin/kexin type 9 gene, PCSK9. The National Lipid Association Expert Panel on Familial Hypercholesterolemia has provided recommendations for the screening and treatment of patients with FH. Early identification and aggressive treatment of FH in individual patients, as well as screening of all first-degree relatives, are recommended to minimize the risk for premature CHD. Similar to patients with conventional hypercholesterolemia, patients with FH should receive statins as initial treatment, but patients with FH may require higher doses of statins, more potent statins, statin-based combination therapy, or adjunctive therapies. Patients with FH who have additional risk factors for, or existing, cardiovascular disease or those with an inadequate response to initial statin therapy should have access to higher doses of the most efficacious statins; statins used in combination with other LDL-C-lowering agents should also be supported by formularies; additional treatments, such as LDL-C apheresis or novel therapies, may also be required to achieve acceptable LDL-C levels. New treatment approaches include mipomersen, which was approved by the FDA in January 2013. Mipomersen is an oligonucleotide inhibitor of apolipoprotein B-100 synthesis (called an antisense inhibitor) indicated as an adjunct to lipid-lowering medications and diet to reduce LDL-C, apolipoprotein B, total cholesterol, and non-high density lipoproteincholesterol (non-HDL-C) levels in patients with homozygous FH (HoFH). The microsomal transfer protein lomitapide has also received FDA approval for use only in patients with HoFH. Other novel treatments currently in development include PCSK9 inhibitors. Therapies such as apheresis are likely more expensive than simple therapy with a statin but may be needed to achieve long-term reductions in complications from nonfatal and fatal cardiovascular events and hospitalizations related to myocardial infarction, cardiac revascularization, and stroke in FH patients. The cost-effectiveness of this more aggressive therapy has not been determined and should be studied. Utilization of published guidelines and the recommendations from the National Lipid Association will help to optimize the management of patients with FH.

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Current management of severe homozygous hypercholesterolaemias

Cited by 88 publications

References 93 publications

The Agenda for Familial Hypercholesterolemia

The Agenda for Familial Hypercholesterolemia

Guidelines for the Management of Familial Hypercholesterolemia

Management of Familial Hypercholesterolemia: A Review of the Recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia

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