Filardi Pasquale Perrone, Paolillo Stefania, Trimarco Bruno
G Ital Cardiol (Rome). 2015 Jan;16(1):44-51. doi: 10.1714/1776.19250.
Low-density lipoprotein (LDL)-cholesterol levels are strictly related to the risk of major cardiovascular events. Statins have been demonstrated to significantly reduce LDL-cholesterol levels, contributing to cardiovascular risk reduction especially in high-risk patients. However, low adherence to statins, due to adverse effects, is often observed and many patients in secondary prevention exhibit LDL-cholesterol levels >70 mg/dl. As a consequence, there is the need for new therapeutic approaches with different mechanisms of action to reach recommended lipid targets in high-risk patients. One potential approach is to inhibit PCSK9, a serum protein with an active role in controlling the expression of LDL receptors, by reducing their recycling and targeting it for lysosomal destruction. Monoclonal antibodies against PCSK9, in particular alirocumab and evolocumab, have been shown to reduce LDL substantially, either with or without concomitant statin therapy with good tolerability. Ongoing trials will further define the efficacy of these drugs as an emerging approach to the treatment of hypercholesterolemia in primary and secondary prevention of high-risk patients.
低密度脂蛋白（LDL）胆固醇水平与主要心血管事件风险密切相关。他汀类药物已被证明能显著降低LDL胆固醇水平，尤其在高危患者中有助于降低心血管风险。然而，常观察到由于不良反应导致对他汀类药物的依从性较低，许多二级预防患者的LDL胆固醇水平>70mg/dl。因此，需要采用具有不同作用机制的新治疗方法，以使高危患者达到推荐的血脂目标。一种潜在方法是抑制前蛋白转化酶枯草溶菌素9（PCSK9），这是一种血清蛋白，通过减少LDL受体的再循环并将其靶向溶酶体降解，在控制LDL受体表达方面发挥积极作用。抗PCSK9单克隆抗体，特别是阿利西尤单抗和依洛尤单抗，已显示出能显著降低LDL，无论是否联合他汀类药物治疗，耐受性良好。正在进行的试验将进一步明确这些药物作为高危患者一级和二级预防中高胆固醇血症新兴治疗方法的疗效。
