Attainment of LDL-C treatment target in familial hypercholesterolemia patients: A theoretical model exploring efficacy of current and novel lipid lowering therapies

2016 ◽  
Vol 252 ◽  
pp. e43-e44 ◽  
Author(s):  
M.L. Hartgers ◽  
J. Besseling ◽  
G.K. Hovingh
Keyword(s):  
Theoretical Model ◽  
Familial Hypercholesterolemia ◽  
Lipid Lowering ◽  
Treatment Target

Abstract 406: Achievement of Treatment Target in Korean Patients With Familial Hypercholesterolemia

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Chan Joo Lee ◽  
Jaewon Oh ◽  
Jung Sun Kim ◽  
Sang-Hak Lee
Keyword(s):  
Total Cholesterol ◽  
Familial Hypercholesterolemia ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Treatment Target ◽  
Evaluation Point ◽  
The Mean ◽  
Artery Disease ◽  
Primary Evaluation

Background: In many cases of familial hypercholesterolemia (FH), there remains difficulty in achievement of treatment target. However, despite growing attention to FH, data on the treatment and its results in these patients are very limited. Methods: From nine sites in Korea, 122 consecutive unrelated men and women who were diagnosed with heterozygous FH by Simon Broome criteria were initially enrolled. Atorvastatin 20 mg or similar-potency drugs were prescribed and the dose was escalated every 2 months (for the first 6 months) or 6 months (thereafter) if needed. Forty one subjects were dropped and 81 subjects who underwent regular laboratory check-up were finally analyzed. The primary evaluation points were achievement rates of low-density lipoprotein cholesterol (LDL-C) <70 mg/dL, LDL-C<100 mg/dL, and LDL-C down to 50% of baseline levels at 12 month. The secondary evaluation point was % change of LDL-C at 12 month. Results: Patients’ mean age was 53 years and 59.3% were males. 21.0% were definite type FH and 28.4% had coronary artery disease (CAD). The mean total cholesterol and LDL-C were 319 mg/dL and 232 mg/dL, respectively. At 12 month, 7.4% received atorvastatin 10mg or similar, 21.0% received atorvastatin 20mg or similar, 16.0% received atorvastatin 40mg or similar, 4.9% received atorvastatin 80mg or similar, and 49.4% received atorvastatin (mean 57 mg) or similar plus ezetimibe 10mg. The mean follow-up total cholesterol and LDL-C were 201 mg/dL and 124 mg/dL, respectively. The mean % change of LDL-C was -45.6%. The achievement rates of LDL-C<70 mg/dL, <100 mg/dL, and LDL-C down to 50% of baseline were 1%, 21%, and 44%, respectively. The achievement rates were not significantly different between the patients without or with CAD (1.8%, 26.3%, 47.4% vs. 0%, 8.7%, 34.8%, respectively, all p values > 0.05). Conclusions: The achievement rate of treatment target in FH was low in Korea even after maximum tolerable dose of lipid lowering drugs. Improvement of awareness on this issue and more aggressive treatment are needed for this population.

Nine-year overview of dyslipidemia management in children with heterozygous familial hypercholesterolemia: a university hospital outpatient lipid clinic project in Northwestern Greece

2020 ◽  
Vol 33 (4) ◽  
pp. 533-538
Author(s):  
Thomas Benekos ◽  
Chrysoula Kosmeri ◽  
Antonios Vlahos ◽  
Haralampos Milionis
Keyword(s):  
Familial Hypercholesterolemia ◽  
Tertiary Hospital ◽  
University Hospital ◽  
Lipid Lowering ◽  
Efficacy And Safety ◽  
Treatment Target ◽  
Heterozygous Familial Hypercholesterolemia ◽  
Lipid Clinic ◽  
Male Sex ◽  
Northwestern Greece

AbstractBackgroundTo assess the efficacy and safety of lipid-lowering treatment in children with heterozygous familial hypercholesterolemia (HeFH) aged ≤12 years attending a tertiary hospital-based outpatient lipid clinic.MethodsData in 318 children from the University Hospital of Ioannina (Northwestern Greece) Outpatient Lipid Clinic Project for Children and Adolescents with Dyslipidemia from March 2009 to December 2018 were analyzed. We assessed the efficacy and safety treatment alongside any possible predictors of the achievement of the treatment target.ResultsOf 318 children with hyperlipidemia, 72 were diagnosed having HeFH based on clinical criteria and genetic confirmation. Compared with non-familial hypercholesterolemia (non-FH) children, those with FH had a higher occurrence of positive family history of premature cardiovascular disease, and higher levels of total, low-density lipoprotein-cholesterol (LDL-C), apolipoprotein B (apoB) and lipoprotein (a) (Lp(a)). Treatment regimens included either atorvastatin 10–20 mg/day, rosuvastatin 5–10 mg/day, pitavastatin 2–4 mg/day monotherapy or in combination with ezetimibe. The treatment goal of LDL-C (<135 mg/dL, 3.5 mmol/L) was achieved in 69% of children treated. The achievement of the treatment targets correlated positively with male sex and inversely with the Dutch Lipid Clinic Network Score, baseline total, LDL-C and apoB levels. No clinically significant changes in liver or muscle-related laboratory tests were reported; no effect on growth or sexual maturation was noted.ConclusionsThis study confirms that lipid-lowering treatment in HeFH children initiated in the setting of a specialized tertiary hospital-based outpatient lipid clinic is efficacious and safe. Children of male sex and low baseline lipid values had a better achievement of treatment target.

Coronary Artery Calcium and Cardiovascular Events in Patients With Familial Hypercholesterolemia Receiving Standard Lipid-Lowering Therapy

2019 ◽  
Vol 12 (9) ◽  
pp. 1797-1804 ◽  
Author(s):  
Marcio H. Miname ◽  
Marcio Sommer Bittencourt ◽  
Sérgio R. Moraes ◽  
Rômulo I.M. Alves ◽  
Pamela R.S. Silva ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Familial Hypercholesterolemia ◽  
Coronary Artery Calcium ◽  
Cardiovascular Events ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Lowering Therapy

scholarly journals FAMILIAL HYPERCHOLESTEROLEMIA: DIAGNOSTIC ISSUES AND THERAPEUTIC POSSIBILITIES

2019 ◽  
Vol 26 (1) ◽  
pp. 175-186
Author(s):  
Vitalii K. Zafiraki ◽  
Alim M. Namitokov ◽  
Elena D. Kosmacheva
Keyword(s):  
Familial Hypercholesterolemia ◽  
Conflict Of Interest ◽  
Screening Program ◽  
Genetic Defect ◽  
Clinical Manifestations ◽  
Density Lipoprotein ◽  
Premature Death ◽  
Lipid Lowering ◽  
Monogenic Disease ◽  
Lipid Lowering Therapy

Familial hypercholesterolemia (FHC) is a common monogenic disease that occurs with a frequency of ~1:250 and is characterised by a high content of low-density lipoprotein (LDL) in the blood. This disease leads to the early development of atherosclerotic cardiovascular diseases (ACVD). Although the screening and diagnostics issues concerned with FHC are well developed and the modern lipid-lowering therapy can significantly improve the prognosis, the detectability of this disease remains extremely low. In recent years, the concept of FHC has undergone significant changes under the influence of large epidemiological studies, including verification of the FHC diagnosis using genetic tests. The article is aimed at discussing the clinical manifestations of FHC, as well as modern medical and extracorporal approaches to its treatment.Conclusion.Until the advent of modern lipid-lowering drugs, FHC had remained to be a disease with a poor prognosis due to early ACVD and the associated premature death. Today, the diseases is amenable to successful treatment, which, though not eliminating the genetic defect, allows almost the same life duration as in the general population to be achieved. However, all the possibilities of modern approaches to the treatment of this serious disease can be realized provided that a state-level screening program for such patients has been implemented.Conflict of interest: the authors declare no conflict of interest.

scholarly journals Rare Treatments for Rare Dyslipidemias: New Perspectives in the Treatment of Homozygous Familial Hypercholesterolemia (HoFH) and Familial Chylomicronemia Syndrome (FCS)

2021 ◽  
Vol 23 (11) ◽  
Author(s):  
Laura D’Erasmo ◽  
Simone Bini ◽  
Marcello Arca
Keyword(s):  
Familial Hypercholesterolemia ◽  
Treatment Options ◽  
New Drugs ◽  
Lipid Lowering ◽  
Homozygous Familial Hypercholesterolemia ◽  
Published Evidence ◽  
Novel Drugs ◽  
Life Threatening ◽  
History Of ◽  
Definition Of

Abstract Purpose of Review This review aims to summarize the most recent published literature concerning lomitapide and volanesorsen that are approved for the use in HoFH and FCS patients, respectively. Moreover, it will briefly revise the published evidence on novel, non-approved treatments that are under evaluation for the management of these rare forms of dyslipidemias Recent Findings The definition of rare dyslipidemias identifies a large number of severe disorders of lipid metabolism of genetic origin. Among them were homozygous familial hypercholesterolemia (HoFH) (OMIM #143890) and familial chylomicronemia syndrome (FCS) (OMIM #238600), which are characterized by a markedly impaired cholesterol- and triglyceride-containing lipoproteins metabolism. They are being particularly associated with poor health outcomes and quality of life. Considering the severity of these diseases, common lipid-lowering drugs are often ineffective or do not allow to achieve the recommended lipid targets to prevent the development of complications. Nowadays, several new drugs have been found to effectively treat HoFH and FCS with an acceptable safety profile. Summary Treating patients with HoFH and FCS remains very challenging. However, novel treatment options are emerging and might be considered in addition to conventional therapy for managing these diseases. These novel drugs will possibly change the natural history of these two rare and life-threatening diseases.

scholarly journals Monoclonal Antibodies in the Management of Familial Hypercholesterolemia: Focus on PCSK9 and ANGPTL3 Inhibitors

2021 ◽  
Vol 23 (12) ◽  
Author(s):  
Angela Pirillo ◽  
Alberico L. Catapano ◽  
Giuseppe D. Norata
Keyword(s):  
Monoclonal Antibodies ◽  
High Risk ◽  
Familial Hypercholesterolemia ◽  
Plasma Levels ◽  
Low Density Lipoprotein ◽  
Genetic Defect ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Low Density ◽  
Premature Cardiovascular Disease

Abstract Purpose of Review Familial hypercholesterolemia (FH) is a monogenic disorder characterized by high plasma levels of low-density lipoprotein cholesterol (LDL-C) since birth and a high risk of premature cardiovascular disease. The genetic defect is carried in only one allele in heterozygous FH (HeFH) or in both in the most severe homozygous FH (HoFH). Current guidelines recommend to reduce substantially LDL-C levels in these high-risk patients, with the need to use association therapy combining agents with different mechanisms of action. As most cases of FH are attributable to mutations in the gene encoding the low-density lipoprotein receptor (LDLR), statins, even in combination with ezetimibe, are less effective in reducing LDL-C plasma levels in FH patients, who require a more intensive approach with additional lipid-lowering agents. Additional targets playing key roles in regulating LDL-C levels are represented by PCSK9 and ANGPTL3. Recent Findings Two monoclonal antibodies (mAbs) targeting PCSK9, evolocumab and alirocumab, significantly reduce LDL-C levels in HeFH patients. In patients with HoFH, the efficacy of mAbs to PCSK9 is strictly related to the presence of a residual LDLR activity; thus, patients carrying null mutations do not respond to the therapy with these mAbs, whereas some effects can be appreciated in HoFH bearing defective mutations. Conversely, evinacumab, the mAb targeting ANGPTL3, is highly effective in reducing LDL-C levels even in HoFH patients carrying null LDLR mutations, thanks to its LDLR-independent mechanism of action. Summary Monoclonal antibodies inhibiting PCSK9 have shown a robust effect in FH patients presenting a residual LDLR activity, while ANGPTL3 inhibitors appear to be promising even in patients carrying null LDLR mutations.

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