Una historia resumida. La inhibición de la PCSK9 y su desarrollo clínico

José López-Sendón, Almudena Castro, Regina Dalmau
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引用次数: 5

Abstract

Hypercholesterolaemia is one of the major cardiovascular risk factors; however, conventional treatment with diet, exercise and cholesterol-lowering drugs are insufficient to control low-density lipoprotein (LDL) cholesterol in a significant number of patients. Inhibition of the PCSK9 protein by using specific monoclonal antibodies increases the number of LDL cholesterol receptors in the hepatocyte, contributing to LDL destruction. The use of these drugs, whether as monotherapy or in combination with statins and ezetimibe, significantly reduces LDL cholesterol, allowing LDL cholesterol levels in most patients to be maintained within limits recommended by clinical practice guidelines. To determine their clinical efficacy, 3 multicenter trials of morbidity and mortality have been conducted with alirocumab, evolocumab and bococizumab. The trial involving evolocumab, a fully human monoclonal antibody, demonstrated a significant reduction of the primary efficacy endpoint, including cardiovascular mortality, myocardial infarction, stroke, unstable angina or myocardial revascularisation. However, no clinical benefit was observed with bococizumab (a humanised but not fully human monoclonal antibody), probably due to a decrease in efficacy secondary to the formation of anti-drug antibodies. This new therapeutic option is already used in clinical practice and is considered a new advance in the prevention of cardiovascular disease.

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一个简短的故事。PCSK9的抑制及其临床发展
高胆固醇血症是心血管疾病的主要危险因素之一;然而,传统的饮食、运动和降胆固醇药物治疗不足以控制大量患者的低密度脂蛋白(LDL)胆固醇。使用特异性单克隆抗体抑制PCSK9蛋白可增加肝细胞中LDL胆固醇受体的数量,从而促进LDL的破坏。这些药物的使用,无论是单独治疗还是与他汀类药物和依折替米布联合使用,都能显著降低低密度脂蛋白胆固醇,使大多数患者的低密度脂蛋白胆固醇水平维持在临床实践指南推荐的范围内。为了确定它们的临床疗效,用alirocumab、evolocumab和bococizumab进行了3项发病率和死亡率的多中心试验。这项涉及evolocumab(一种全人源单克隆抗体)的试验显示,主要疗效终点显著降低,包括心血管死亡率、心肌梗死、中风、不稳定型心绞痛或心肌血运重建。然而,bococizumab(一种人源化但不是完全人源化的单克隆抗体)没有观察到临床益处,可能是由于抗药物抗体的形成导致疗效下降。这种新的治疗选择已经在临床实践中使用,被认为是预防心血管疾病的新进展。
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来源期刊
Revista Espanola de Cardiologia Suplementos
Revista Espanola de Cardiologia Suplementos Medicine-Cardiology and Cardiovascular Medicine
CiteScore
1.20
自引率
0.00%
发文量
1
期刊介绍: Revista Española de Cardiología, is an international scientific journal dealing with cardiovascular medicine. Revista Española de Cardiología, the official publication of the Spanish Society of Cardiology, publishes research articles related to cardiovascular diseases. Articles are published in Spanish for the paper edition and in both Spanish and English in the electronic edition, which is available on the Internet. Regular sections include original articles reporting clinical or basic research, brief reports, review articles, editorials and letters to the Editor.
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