Application of the MCDA method for assessing new technologies for familial hypercholesterolaemia treatment / Aplicação do método MCDA para avaliar novas tecnologias para o tratamento da hipercolesterolemia familiar

Objective: Familial hypercholesterolaemia is a hereditary disease characterized by very high levels of low-density lipoprotein cholesterol and an elevated risk of early-onset cardiovascular disorders. New drugs provide alternatives for the treatment of patients with homozygous familial hypercholesterolaemia. The study aims to explore a practical application of multiple-criteria decision analysis on prioritization of new and emerging technologies for familial hypercholesterolaemia. Methods: The decision model was constructed using the MACBETH method. There were three stages: structuring the problem, measuring the performance of alternatives, and building the model. The weights for alternatives and levels were obtained by indirect comparisons, which evaluated the attractiveness of the performance levels of the criteria using the swing weights technique. Results: The drugs lomitapide, ezetimibe, evolocumab, and mipomersen were selected as alternatives for decision-making. "Cardiovascular Death", "Stroke" and "Acute Myocardial Infarction" had the three most significant weights. The criteria with the lowest weights were "Comfort" and "LDL-C Reduction". The top-ranked technology was evolocumab, with an overall score of 59.87, followed by ezetimibe, with a score of 37.21. Conclusion: How to apply the result of a higher score in the actual decisionmaking process still requires further studies. The case in question showed that evolocumab has more performance benefits than other drugs but with a cost approximately 50 times higher

Objetivo: A hipercolesterolemia familiar é uma doença hereditária caracterizada por níveis muito elevados de lipoproteína de baixa densidade (LDL-colesterol) e um risco elevado de doenças cardiovasculares de início precoce. Novos medicamentos oferecem alternativas para o tratamento de pacientes com hipercolesterolemia familiar homozigótica. Esse estudo tem como objetivo explorar uma aplicação prática da análise de decisão multicritério na priorização de tecnologias novas e emergentes para hipercolesterolemia familiar. Métodos: O modelo de decisão foi construído usando o método MACBETH. Três etapas foram criadas: estruturação do problema, mensuração do desempenho das alternativas e construção do modelo. Os pesos para alternativas e níveis foram obtidos por comparações indiretas, que avaliaram a atratividade dos níveis de desempenho dos critérios usando a técnica de pesos de balanço. Resultados: Os medicamentos lomitapida, ezetimiba, evolocumabe e mipomersen foram selecionados como alternativas para a tomada de decisão. "Morte Cardiovascular", "Acidente vascular cerebral" e "Infarto Agudo do Miocárdio" tiveram os três pesos mais significativos. Os critérios com os menores pesos foram "Conforto" e "Redução do LDL-C". A tecnologia mais bem avaliada foi o evolocumabe, com pontuação geral de 59,87, seguido da ezetimiba, com pontuação de 37,21. Conclusão: Ainda são necessários estudos para determinar como aplicar o resultado de uma pontuação mais alta no processo de tomada de decisão. O caso em questão demonstrou que o evolocumabe tem benefícios mais significativos em relação aos outros medicamentos, mas com um custo cerca de 50 vezes maior

A successful pregnancy outcome of homozygous familial hypercholesterolaemia patient on statin therapy

@#Homozygous familial hypercholesterolaemia (HoFH) is a rare genetic disorder of lipoprotein metabolism mainly due to mutation of the low-density lipoprotein (LDL)-receptor gene (LDLR). It is a life-threatening disease that causes accelerated, multi-vessel atherosclerosis presented in early childhood. Pregnancy in HoFH may pose early coronary morbidity and mortality to both the foetus and mother. The combination of HoFH and pregnancy can be a fatal condition. While statins are very effective in lowering low-density lipoprotein cholesterol (LDL-C) levels, they are generally contraindicated during pregnancy, thus their use during pregnancy is uncommon. On the other hand, lipid apheresis (LA) has turned into an effective treatment to control cholesterol level amid pregnancy. However, the procedure is not widely available in our region. To date, there are scarcely documented case reports of HoFH in pregnancy in which the majority of them underwent LA to keep LDL-C at a low level. We report a rare case of successful pregnancy outcome of HoFH patient treated with lipid-lowering drugs including statin without LA therapy. Apart from that, we also discussed the genetic findings of the proband and all screened family members in which to the best of our knowledge, the first study using the whole-exome sequencing technique to identify the causative gene mutations for familial hypercholesterolaemia among the Malaysian population.

Updates in the management of Dyslipidaemia in the high and very high risk individual for CV risk reduction

mortality and an important cause of morbidity in Malaysiafor several years. To reduce global cardiovascular (CV) riskin the population, primary preventive strategies need to beimplemented. Hypercholesterolaemia is one of the majorrisk factors for CVD. This paper is an expert review on themanagement of hypercholesterolemia focusing on high andvery high risk individuals. In low and Intermediate riskindividuals, therapeutic lifestyle changes (TLC) and ahealthy lifestyle alone may suffice. In high and very high riskindividuals, drug therapy in conjunction with TLC arenecessary to achieve the target LDL-C levels which havebeen shown to slow down progression and sometimes evenresult in regression of atherosclerotic plaques. Statins arefirst-line drugs because they have been shown in numerousrandomized controlled trials to be effective in reducing CVevents and to be safe. In some high risk individuals, despitemaximally tolerated statin therapy, target Low DensityLipoprotein Cholesterol (LDL-C) levels are not achieved.These include those with familial hypercholesterolaemia andstatin intolerance. This paper discusses non-statintherapies, such as ezetimibe and the newer Proproteinconvertase subtilisin/kexin type 9 Inhibitors (PCSK9-i).

Hipercolesterolemia familiar heterocigota en manejo con anti-PCSK9 / Heterozygous familial hypercholesterolaemia being managed with anti-PCSK9

Resumen Introducción: la hipercolesterolemia familiar representa un factor de riesgo sustancial para padecer enfermedad coronaria prematura, arterial periférica y valvular. Se han descrito dos formas según su alteración genética y cigocidad, así como tres mutaciones genéticas asociadas. Pese a que el tratamiento con estatinas se considera la primera línea, algunos pacientes no alcanzan metas, de modo que se han utilizado los inhibidores del PCSK9 como nueva estrategia. Métodos y materiales: se expone el caso de una paciente de 42 años con hipercolesterolemia familiar heterocigota tratada con inhibidores del PCSK9. Se describen los criterios y estudiosgenéticos utilizados para realizar el diagnóstico, la cronología de tratamientos que recibió y los exámenes de laboratorio anteriores y posteriores al inicio del evolocumab. Adicionalmente se hace una revisión de tema acerca de la hipercolesterolemia familiar y su tratamiento con inhibidores del PCSK9. Conclusiones: la hipercolesterolemia familiar es una enfermedad que ocasiona graves consecuencias cardiovasculares. Los inhibidores del PCSK9 se han convertido en una alternativa prometedora para aquellos que no responden a las terapias convencionales. Se requieren estudios que corroboren o contradigan los beneficios y eventos adversos encontrados hasta el momento en que los pacientes se someten a estas nuevas terapias para así ofrecer un tratamiento ideal y oportuno.

Abstract Introduction: Familial hypercholesterolaemia is a substantial risk factor for suffering premature coronary, peripheral arterial, and valular disease. There are two forms described, depending on their genetics and zygosity, as well as three associated genetic mutations. Although treatment with statins is considered first line, some patients do not reach targets, as such that that PCSK9 inhibitors have been used as a new strategy. Materials and method: A case is presented of a 42 year-old patient with heterozygous familial hypercholesterolaemia treated with PCSK9 inhibitors. The criteria and genetic studies used to make a diagnosis are described, as well as the chronology of the treatments that have been received and the laboratory results before and after starting with evolocumab. A review has also been made of the subject of familial hypercholesterolaemia and its treatment with PCSK9 inhibitors. Conclusions: Familial hypercholesterolaemia is a diseases that may have serious cardiovascular consequences. PCSK9 inhibitors have become a promising alternative for those who do not respond to conventional therapies. Studies are required that can corroborate or contradict the benefits and adverse effects found up until now in patients subjected to these new therapies in order to offer an ideal and appropriate treatment.

Homozygous Familial Hypercholesterolaemia with Valvular Aortic Stenosis and Significant Coronary Artery Disease: A Case Report.

Homozygous Familial Hypercholesterolaemia is a genetic disorder which usually presents with early cardiovascular disease ranging from premature ischaemic disease, including myocardial infarction to aortic root stenosis. A 21 year old Bangladeshi male presented with exertional chest pain and breathlessness. He was diagnosed as a case of Homozygous Familial Hypercholesterolaemia. His angina symptoms were due to underlying valvular aortic stenosis which is a rare presentation of Homozygous Familial Hypercholesterolaemia.

Relación entre ll metabolismo de los triglicérios y aterosclerosis en la hiperrcolesterolemia familarr / Relationsip betwween the triglycerides metabolism and athrosclerosis in familial hypercholesterolemia

La hipercolesterolemia familiar (HF) es un desorden genético, que afecta en la forma heterocigota a uno de cada 500 nacimientos. Está asociado a aterosclerosis, debido a la elevación de las concentraciones de Lipoproteínas de Baja Densidad (LDL), además se han reportado niveles elevados de triglicéridos, e hipertrigliciridemia postprandrial, como posible factor de riesgo independiente para aterosclerosis. En el presente artículo de revisión, se analizó la literatura disponible en la base de datos, al igual que artículos históricos, textos y referencias citadas en trabajos públicos, buscando analizar la relación entre el metabolismo de los triglicéridos en la hipercolesterolemia familiar y la aterosclerosis. La información obtenida se organizó teniendo en cuenta: metabolismo de triglicéridos, metabolismo de triglicéridos en la hipercolesterolemia familiar y aterosclerosis. Dentro de las conclusiones obtenidas se encontró que los niveles elevados de triglicéridos se asocian con un alto riesgo de enfermedad cardiaca coronaria prematura en pacientes con HF.

Familial hypercholesterolaemia (FH) is a genetic disorder, with the heterozygous form affecting one in 500 deliveries. FH is associated with atherosclerosis due to elevated LDL concentrations but also, triglyceride levels and postprandial hypertriglyceridemia have been reported as possible independent risk factors for atherosclerosis. In the present review article available literature in the data basesinformation from database PubMed as well as historical articles, texts and references cited in public published papers to date were analyzed, searching a possible relationship between triglyceride metabolism in FH and atherosclerosis. The information obtained was organizedPertinent information related with the objectives proposed in the present review was found and analyzed. It was then divided into three sections as follows: triglyceride metabolism, triglyceride metabolism in familiar hypercholesterolaemia, triglycerides in familiar hypercholesterolaemia and atherosclerosis. Among the conclusions iIt was found that can be concluded that high levels of triglycerides are associated to with high risk of early coronary heart disease in FH patients.