VA Medical Center and Georgetown University, Washington, DC, United States.
2nd Prop Department of Internal Medicine, Aristotle University, Thessaloniki, Greece.
Curr Pharm Des. 2018;24(31):3647-3653. doi: 10.2174/1381612824666181010124657.
Familial hypercholesterolemia (FH) is an inherited autosomal dominant disorder that is characterized by substantially increased Low-Density Lipoprotein Cholesterol (LDL-C) levels. Patients with FH have a significantly higher risk for Cardiovascular (CV) events, and the timely reduction of LDL-C is of paramount importance to ameliorate the risk for CV disease. Among the available lipid-lowering therapies, the novel Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors have emerged as a very promising class of drugs for the management of such patients.
The purpose of this review is to present available data on the efficacy and safety of the two available PCSK9 inhibitors in patients with FH, and importantly to discuss potential differences between the two drugs.
A comprehensive literature search was performed to identify available data from clinical studies evaluating the impact of evolocumab or alirocumab on lipid and CV parameters in patients with FH.
Several studies have assessed the lipid-lowering profile of PCSK9 inhibitors in patients with FH. Both evolocumab and alirocumab were found to significantly reduce LDL-C by more than 50-60% in FH patients. Furthermore, data also support a lower rate of lipid apheresis in FH patients receiving a PCSK9 inhibitor. In terms of CV outcomes, both drugs were found to possess CV-ameliorating effects of the same extent in patients with CV disease. However, alirocumab reduced all-cause mortality, as well, a finding not observed with evolocumab. Several differences in the study population characteristics might explain this and other mild differences observed in the CV trials of these drugs.
Available evidence suggests similar potency of alirocumab and evolocumab in reducing lipids and CV events.
家族性高胆固醇血症（FH）是一种常染色体显性遗传疾病，其特征是低密度脂蛋白胆固醇（LDL-C）水平显著升高。FH 患者发生心血管（CV）事件的风险显著增加，及时降低 LDL-C 对于改善 CV 疾病风险至关重要。在可用的降脂治疗中，新型前蛋白转化酶枯草溶菌素/柯萨奇蛋白酶 9（PCSK9）抑制剂已成为此类患者治疗的一类很有前途的药物。
本综述旨在介绍两种可用的 PCSK9 抑制剂在 FH 患者中的疗效和安全性数据，并重要的是讨论两种药物之间的潜在差异。
进行了全面的文献检索，以确定评估依洛尤单抗或阿利西尤单抗对 FH 患者血脂和 CV 参数影响的临床研究中的可用数据。
多项研究评估了 PCSK9 抑制剂在 FH 患者中的降脂谱。依洛尤单抗和阿利西尤单抗均被发现可使 FH 患者的 LDL-C 降低 50%以上。此外，数据还支持 FH 患者接受 PCSK9 抑制剂治疗时，血脂吸附的频率较低。就 CV 结局而言，这两种药物在 CV 疾病患者中均具有相同程度的 CV 改善作用。然而，阿利西尤单抗还降低了所有原因的死亡率，而依洛尤单抗则没有观察到这种作用。研究人群特征的一些差异可能解释了这一点，以及这些药物的 CV 试验中观察到的其他轻微差异。
现有证据表明，阿利西尤单抗和依洛尤单抗在降低血脂和 CV 事件方面具有相似的效力。
