Hassan Mohamed
Division of Cardiology, Aswan Heart Centre, Aswan, Egypt.
Glob Cardiol Sci Pract. 2015 Jun 26;2015(2):20. doi: 10.5339/gcsp.2015.20. eCollection 2015.
Proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors have emerged as a novel treatment option in patients with hypercholesterolemia. Evolocumab and alirocumab have achieved consistent and significant (around 60%) reduction in low-density lipoprotein cholesterol (LDL-C) levels when added to statin therapy in short term studies. The Open-Label Study of Long-term Evaluation Against LDL-C (OSLER), and The Long-term Safety and Tolerability of Alirocumab in High Cardiovascular Risk Patients with Hypercholesterolemia Not Adequately Controlled with Their Lipid Modifying Therapy (ODYSSEY LONG TERM) studies are two phase 3, multicentre, randomized, placebo controlled studies that were conducted to evaluate the long term efficacy and safety of evolocumab and alirocumab respectively in reducing lipids and cardiovascular (CV) events. Both studies demonstrated additional 48-53% reduction of CV events when added to statin therapy. Most adverse events occurred with similar frequency in the two groups; however the rate of neurocognitive adverse events was higher with evolocumab and alirocumab than with placebo. These data provide strong support for the notion that lower LDL-C goal is better, and may confirm the role of PCSK9 inhibitors as a new frontier in lipid management. The results of larger long-term outcome studies are still awaited.
前蛋白转化酶枯草溶菌素9（PCSK9）抑制剂已成为高胆固醇血症患者的一种新型治疗选择。在短期研究中，阿利西尤单抗和依洛尤单抗与他汀类药物联合使用时，可使低密度脂蛋白胆固醇（LDL-C）水平持续且显著（约60%）降低。“评估降低LDL-C的长期开放标签研究（OSLER）”以及“阿利西尤单抗在血脂调节治疗未充分控制的高心血管风险高胆固醇血症患者中的长期安全性和耐受性研究（ODYSSEY长期研究）”是两项3期、多中心、随机、安慰剂对照研究，分别旨在评估依洛尤单抗和阿利西尤单抗在降低血脂和心血管（CV）事件方面的长期疗效和安全性。两项研究均表明，与他汀类药物联合使用时，CV事件可额外减少48%-53%。两组中大多数不良事件的发生频率相似；然而，依洛尤单抗和阿利西尤单抗组的神经认知不良事件发生率高于安慰剂组。这些数据为更低的LDL-C目标更好这一观点提供了有力支持，并可能证实PCSK9抑制剂作为脂质管理新前沿的作用。更大规模长期结局研究的结果仍有待观察。
