苯二甲酸和他汀类药物降脂策略:哪个先有蛋还是先有鸡?

F. Natale, R. Molinari, Rosa Franzese, N. Mollo, G. Cimmino
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摘要

预防心血管疾病的目标是通过在一般人群中提倡健康的生活方式来降低发病率和死亡率。基于个体风险,采用药物和非药物干预措施管理可改变的风险因素是当前指南建议的第一种策略。一些流行病学研究清楚地表明,低密度脂蛋白胆固醇(LDL-C)的高水平与心血管疾病的发病率之间存在直接关联。另一方面,大量随机临床研究报告了LDL-C降低对主要心血管事件的巨大益处,从而支持了“越低越好”的观点。在降脂策略中,他汀类药物是心血管预防的首选药物,无论是一级还是二级。为了实现当前指南所建议的宏伟目标,除了他汀类药物之外,目前还可以使用其他降脂疗法,例如PCSK9抑制剂依zetimibe。最近的药理学研究导致了一种新药的开发,它进一步丰富了现有的治疗方法。这种药物也作用于胆固醇的生物合成,但作用水平比他汀类药物高。从生化的角度来看,在服用他汀类药物之前,有可能考虑到这一点,随后他汀类药物的滴定,以达到理想的LDL-C目标。本文综述了苯二甲酸的生物化学和药理特性。本文还将概述支持其在心血管患者管理中的应用及其在降脂方案中的分配的临床数据。
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Bempedoic Acid and Statins in Lipid-Lowering Strategy: Which Came First, the Egg or the Chicken?
The goal in cardiovascular prevention is the reduction of morbidity and mortality through the promotion of healthy lifestyles in the general population. The management of modifiable risk factors with pharmacological and non-pharmacological interventions, based on the individual risk is the first strategy suggested by the current guidelines. Several epidemiological studies have clearly shown the direct correlation between high levels of low-density lipoprotein cholesterol (LDL-C) and incidence of cardiovascular diseases. On the other hand, numerous randomized clinical studies have reported a huge benefit in terms of major cardiovascular events achievable by the reduction of LDL-C, thus supporting the notion that “the lower is better”. Among the lipid-lowering strategies, statins are the drugs of choice in cardiovascular prevention, at both primary and secondary level. To achieve the ambitious targets suggested by the current guidelines, other lipid-lowering therapies are currently available in addition to statins, such as ezetimibe the inhibitors of the PCSK9. Pharmacological research has recently led to the development of a new drug, the bempedoic acid, which further enrich the available therapies. This drug also acts on the biosynthesis of cholesterol but at upstream level than statins. From the biochemical point of view, it has the potential to be considered before the statin with consequent titration of statins to achieve the desirable LDL-C target. In the present review, the biochemical and pharmacological characteristics of bempedoic acid are discussed. An overview of the clinical data that support its use in the management of the cardiovascular patient and its allocation in the lipid-lowering scenario will be also provided.
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