Lomitapide–a Microsomal Triglyceride Transfer Protein Inhibitor for Homozygous Familial Hypercholesterolemia

Stefanutti, Claudia

doi:10.1007/s11883-020-00858-4

Cited by 41 publications

(28 citation statements)

References 54 publications

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“…tions in LDL-C of more than 50% in many patients and less severe adverse events [98]. Data from the Lomitapide Observational Worldwide Evaluation Registry (LOWER) show that the median dose was 10 mg and the mean reduction in LDL-C was 33% overall, or 45% in patients remaining on lomitapide treatment [99].…”

Section: Article In Pressmentioning

confidence: 99%

Role of PCSK9 Inhibitors in Patients with Familial Hypercholesterolemia

2021

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Patients with familial hypercholesterolemia (FH) are at high or very high risk for cardiovascular disease. Those with heterozygous FH (HeFH) often do not reach low-density lipoprotein cholesterol (LDL-C) targets with statin and ezetimibe therapy, and those with homozygous FH (HoFH) usually require additional lipid-modifying therapies. Drugs that inhibit proprotein convertase subtilisin/ kexin type 9 (PCSK9) offer a novel approach to reduce LDL-C. The monoclonal antibodies, alirocumab and evolocumab, given by subcutaneous injection every 2 or 4 weeks produce reductions in LDL-C of 50% to 60% in patients with HeFH, allowing many of them to achieve their LDL-C goals. Patients with HoFH show a reduced and more variable LDL-C response, which appears to depend on residual LDL receptor activity, and those with receptor-negative mutations may show no response. Inclisiran is a long-acting small interfering RNA therapeutic agent that inhibits the synthesis of PCSK9. Subcutaneous doses of 300 mg can reduce LDL-C by more than 50% for at least 6 months and the responses in HeFH and HoFH patients are similar to those achieved with monoclonal antibodies. These PCSK9 inhibitors are generally well tolerated and they provide a new opportunity for effective treatment for the majority of patients with FH.

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Section: Article In Pressmentioning

confidence: 99%

Role of PCSK9 Inhibitors in Patients with Familial Hypercholesterolemia

2021

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“…In subjects with homozygous FH treated by diet only, the maximum reduction obtained with lomitapide was −51% for LDL-C, −79% for VLDL-C, −65% for TG, − 56% for APOB, and − 15% for Lp (a). However, fatty liver and gastrointestinal side effects occur frequently [ 55 ]. Cholesterol ester transfer protein inhibitors (CETP) (anacetrapib and evacetrapib) reduce transfer of cholesterol esters from high-density lipoprotein (HDL) to VLDL and LDL and the transfer of TG from the latter to HDL.…”

Section: Management Of Homozygous Fhmentioning

confidence: 99%

Current Approach to the Diagnosis and Treatment of Heterozygote and Homozygous FH Children and Adolescents

Cohen

Stefanutti²

2021

Curr Atheroscler Rep

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Purpose of Review To elucidate the current approach of care in pediatric patients with familial hypercholesterolemia (FH). We sought an answer to the question whether the advances and major changes in lipid management are relevant and apply to children and adolescents. Recent Findings Latest research findings clearly demonstrate that lowering cholesterol levels at a young age prevents vascular atherosclerotic changes and decreases cardiovascular events in adulthood and emphasizes the importance of early detection and intervention in the pediatric FH patients group. Summary FH is a common genetic disease caused by mutations in genes associated with the metabolism of low-density lipoproteins (LDL). The hallmark of FH is elevated LDL cholesterol (LDL-C) levels from birth and premature atherosclerotic cardiovascular disease (ASCVD). Often FH is either undiagnosed or diagnosed with a considerable delay, leading to vascular atherosclerotic changes and cardiovascular disease. Prompt identification of FH subjects is essential, to initiate early preventive measures. Safe and efficient pharmacological agents are approved for use in children and adolescents. Statins are the first line of therapy, in combination of ezetimibe. Unfortunately, these drugs do not warrant the achievement of therapeutic target, especially in HoFH patient. In the latter, lipoprotein apheresis (LA), which has been shown to be safe and effective, is strongly recommended. Finally, the new drugs still under study will allow a multimodal customized treatment. Lowering cholesterol levels at a young age hinders vascular atherosclerotic changes decreasing cardiovascular events in adulthood. Therefore, early detection, diagnosis, and intervention in FH patients are priority objectives.

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“…However, as previously mentioned, it has been seen that in the long-term, statins do not have a good safety profile and their efficacy is not as expected, which is why we com-pared them other another drug that was introduced in 2013. The importance of this drug lies in the beneficial effect that it is reported to have in reducing cardiovascular events and therefore in increasing survival [8].…”

Section: Description Of the Interventionmentioning

confidence: 99%

Reducción de eventos cardiovasculares de Lomitapida versus Estatinas en pacientes con diagnóstico de hipercolesterolemia familiar. Protocolo de revisión sistemática.

Valdez

Avila

Espinoza³

et al. 2021

REV-SEP

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Introducción: La hipercolesterolemia familiar (HF) un trastorno genético autosómico dominante que produce hipercolesterolemia y desarrollo prematuro de enfermedades cardiovasculares. Las estatinas han sido el medicamento de elección en estos pacientes, sin embargo, un buen porcentaje de pacientes no pueden alcanzar sus objetivos terapéuticas con las dosis máximas recomendadas por lo que la Lomitapida se podría establecer como una nueva alternativa de tratamiento. Objetivo: El objetivo de esta revisión sistemática es determinar si la Lomitapida reduce los eventos cardiovasculares en pacientes con diagnóstico de Hipercolesterolemia familiar comparado con estatinas. Métodos: Se incluirán ensayos controlados aleatorios (ECA) y cuasialeatorios de pacientes con diagnóstico de HF. Las medidas de resultado primarias: 1. Niveles de LDL, HDL pos tratamiento. 2. Presencia de eventos cardiovasculares. Las búsquedas electrónicas se realizarán en PUBMED, The Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE y Scientific electronic library (Scielo). La evaluación del riesgo de sesgo se utilizará la herramienta de Cochrane. Las medidas del efecto del tratamiento serán las diferencias de medias (DM) y los intervalos de confianza (IC) del 95%. La evaluación de heterogeneidad se realizará mediante la inspección visual del diagrama de embudo. La evaluación de la calidad de la evidencia se realizará usando la evaluación GRADE.

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Lomitapide–a Microsomal Triglyceride Transfer Protein Inhibitor for Homozygous Familial Hypercholesterolemia

Cited by 41 publications

References 54 publications

Role of PCSK9 Inhibitors in Patients with Familial Hypercholesterolemia

Role of PCSK9 Inhibitors in Patients with Familial Hypercholesterolemia

Current Approach to the Diagnosis and Treatment of Heterozygote and Homozygous FH Children and Adolescents

Reducción de eventos cardiovasculares de Lomitapida versus Estatinas en pacientes con diagnóstico de hipercolesterolemia familiar. Protocolo de revisión sistemática.

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