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Silenciamento de genes para o tratamento da hipercolesterolemia
| Name: | Description: | Size: | Format: | |
|---|---|---|---|---|
| Projeto de pós-graduação_39596 | 1.68 MB | Adobe PDF |
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Abstract(s)
As doenças cardiovasculares (DCV) são uma das principais causas de morte nos países desenvolvidos, sendo a dislipidemia um dos principais fatores de risco cardiovascular. As estatinas constituem uma classe importante da terapia farmacológica da hipercolesterolemia dada a sua eficácia bem documentada na redução da morbilidade e da mortalidade cardiovasculares. No entanto, esta terapêutica mostra-se insuficiente para normalizar os níveis lipídicos de alguns doentes e outros não a toleram devido aos seus efeitos adversos.
O inclisiran, uma pequena molécula de RNA de interferência (siRNA) que promove o silenciamento pós-transcricional da pró-proteína convertase subtilisina/kexina tipo 9 (PSCK9), surgiu como uma nova estratégia para a redução do colesterol e risco cardiovascular. Este siRNA sintético de ação prolongada tem como alvo a produção hepática de PCSK9 e, consequentemente, causa uma redução nas concentrações de C-LDL. Os estudos clínicos, especialmente os ensaios de fase III ORION-10 e ORION-11, demonstraram que o inclisiran reduz significativamente os níveis de C-LDL em aproximadamente 50% em comparação ao placebo. Estes ensaios também destacaram a sua eficácia sustentada com um regime de administração semestral, o que pode melhorar significativamente a adesão ao tratamento.
Em termos de segurança, os ensaios clínicos indicaram que este possui um perfil de segurança favorável. Os efeitos adversos mais comuns relatados foram reações no local da injeção, que geralmente foram leves e transitórias. Não foram observadas diferenças significativas na incidência de eventos adversos graves entre os grupos tratados com inclisiran e placebo.
Já os resultados preliminares indicaram uma redução de aproximadamente 24% nos eventos adversos cardiovasculares major (MACE) em pacientes tratados com inclisiran em comparação com aqueles que receberam placebo. Esta potencial redução de MACE é um indicador promissor de que o inclisiran não só reduz os níveis de C-LDL, como também pode impactar positivamente na redução do risco cardiovascular.
Cardiovascular diseases (CVD) are one of the leading causes of death in developed countries and dyslipidaemia is one of the main cardiovascular risk factors. Statins are an important class of pharmacological therapy for hypercholesterolemia due to their well-documented efficacy in reducing cardiovascular morbidity and mortality. However, this therapy proves to be insufficient to normalise lipid levels in some patients and others cannot tolerate it due to its adverse effects. Inclisiran, a small interfering RNA molecule (siRNA) that promotes post-transcriptional silencing of the pro-protein convertase subtilisin/kexin type 9 (PSCK9), has emerged as a new strategy for reducing cholesterol and cardiovascular risk. This long-acting synthetic siRNA targets the hepatic production of PCSK9 and consequently causes a reduction in LDL-C concentrations. Clinical studies, especially the phase III ORION-10 and ORION-11 trials, have shown that inclisiran significantly reduces LDL-C levels by approximately 50 per cent compared to placebo. These trials also highlighted its sustained efficacy with a six-monthly administration regime, which can significantly improve adhesion to treatment. In terms of safety, clinical trials have indicated that it has a favourable safety profile. The most common adverse effects reported were injection site reactions, which were generally mild and transient. There were no significant differences in the incidence of serious adverse events between the groups treated with inclisiran and placebo. Preliminary results indicated a reduction of approximately 24 per cent in adverse cardiovascular major (MACE) events in patients treated with inclisiran compared to those who received placebo. This potential reduction in MACE is a promising indicator that inclisiran not only reduces LDL-C levels, but may also have a positive impact on reducing cardiovascular risk.
Cardiovascular diseases (CVD) are one of the leading causes of death in developed countries and dyslipidaemia is one of the main cardiovascular risk factors. Statins are an important class of pharmacological therapy for hypercholesterolemia due to their well-documented efficacy in reducing cardiovascular morbidity and mortality. However, this therapy proves to be insufficient to normalise lipid levels in some patients and others cannot tolerate it due to its adverse effects. Inclisiran, a small interfering RNA molecule (siRNA) that promotes post-transcriptional silencing of the pro-protein convertase subtilisin/kexin type 9 (PSCK9), has emerged as a new strategy for reducing cholesterol and cardiovascular risk. This long-acting synthetic siRNA targets the hepatic production of PCSK9 and consequently causes a reduction in LDL-C concentrations. Clinical studies, especially the phase III ORION-10 and ORION-11 trials, have shown that inclisiran significantly reduces LDL-C levels by approximately 50 per cent compared to placebo. These trials also highlighted its sustained efficacy with a six-monthly administration regime, which can significantly improve adhesion to treatment. In terms of safety, clinical trials have indicated that it has a favourable safety profile. The most common adverse effects reported were injection site reactions, which were generally mild and transient. There were no significant differences in the incidence of serious adverse events between the groups treated with inclisiran and placebo. Preliminary results indicated a reduction of approximately 24 per cent in adverse cardiovascular major (MACE) events in patients treated with inclisiran compared to those who received placebo. This potential reduction in MACE is a promising indicator that inclisiran not only reduces LDL-C levels, but may also have a positive impact on reducing cardiovascular risk.
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Keywords
Aterosclerose Hipercolesterolemia PCSK9 siRNA Inclisiran Doenças cardiovasculares Atherosclerosis Hypercholesterolaemia PCSK9 Cardiovascular diseases