Abduljabbar Maram H
Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
Pharmaceuticals (Basel). 2024 Nov 25;17(12):1581. doi: 10.3390/ph17121581.
This paper investigates the therapeutic use of PCSK9 inhibitors, particularly Evolocumab, as monoclonal antibodies for the treatment of atherosclerosis based on recent literature reviews. PCSK9 is an outstanding example of a breakthrough in medical science, with advancements in understanding its biological function driving substantial progress in atherosclerosis treatment. Atherosclerotic cardiovascular disease (ASCVD) is a leading global cause of mortality, imposing substantial financial burdens on healthcare systems. Elevated low-density lipoprotein cholesterol (LDL-C), a modifiable risk factor, plays a pivotal role in the development of ASCVD. Emerging treatments such as PCSK9 inhibitors are now being introduced to combat this issue, with the goal of reducing ASCVD risk by directly targeting LDL-C levels. This discovery highlighted the potential of monoclonal antibodies to inhibit PCSK9, thereby enhancing LDL-C receptor activity. This breakthrough led to the development of Alirocumab and Evolocumab inhibitors, which typically reduce LDL-C levels by approximately 50%. This research underscores the importance of PCSK9 inhibitors in treating ASCVD, drawing on evidence from various randomized controlled trials such as FOURIER, ODYSSEY OUTCOMES, and VESALIUS-CV. These trials have also shown that PCSK9 inhibitors are effective and safe for the treatment of several cardiovascular disorders. PCSK9 inhibitors are therefore useful in patients who do not reach their target LDL-C levels when on the highest doses of statins or patients with very high cardiovascular risk who cannot tolerate statins at all.
本文基于近期的文献综述，研究了前蛋白转化酶枯草溶菌素9（PCSK9）抑制剂，尤其是依洛尤单抗，作为单克隆抗体在动脉粥样硬化治疗中的应用。PCSK9是医学科学突破的一个杰出范例，对其生物学功能认识的进展推动了动脉粥样硬化治疗的重大进步。动脉粥样硬化性心血管疾病（ASCVD）是全球主要的死亡原因，给医疗系统带来了巨大的经济负担。可改变的危险因素——低密度脂蛋白胆固醇（LDL-C）升高，在ASCVD的发生发展中起关键作用。现在正在引入如PCSK9抑制剂等新的治疗方法来应对这一问题，目标是通过直接针对LDL-C水平来降低ASCVD风险。这一发现凸显了单克隆抗体抑制PCSK9的潜力，从而增强LDL-C受体活性。这一突破促成了阿利西尤单抗和依洛尤单抗抑制剂的研发，它们通常可使LDL-C水平降低约50%。本研究利用FOURIER、ODYSSEY OUTCOMES和VESALIUS-CV等各种随机对照试验的证据，强调了PCSK9抑制剂在治疗ASCVD中的重要性。这些试验还表明，PCSK9抑制剂对治疗几种心血管疾病有效且安全。因此，对于服用最大剂量他汀类药物仍未达到目标LDL-C水平的患者，或根本无法耐受他汀类药物的心血管风险极高的患者，PCSK9抑制剂是有用的。
