Punnanithinont Natdanai, Kambalapalli Soumya, Iskander Beshoy, Ichikawa Keishi, Krishnan Srikanth, Lakshmanan Suvasini, Roy Sion K, Budoff Matthew
The Lundquist Institute, UCLA Medical Center Harbor, 1124 W Carson St, CA 90502, Torrance, US.
Curr Atheroscler Rep. 2024 Dec 19;27(1):19. doi: 10.1007/s11883-024-01267-7.
Inflammation has been commonly known for the past decade as a part of the pathophysiology of atherosclerosis, along with lipid accumulation. However, some patients with optimized lipid-lowering therapy still have elevated inflammatory biomarkers. Anti-inflammation therapies were developed to eradicate this residual risk. We summarized the primary inflammatory pathway and recent clinical trials in anti-inflammation therapies.
Colchicine Cardiovascular Outcomes Trial (COLCOT) and LoDoCo2 (Colchicine Reduces Risk of Major Cardiovascular Events in Chronic Coronary Disease) found that low-dose colchicine significantly reduced cardiovascular death, myocardial infarction (MI), ischemic stroke and coronary revascularization in patients with recent MI within 30 days and chronic coronary disease respectively. The US Food and Drug Administration approved low-dose colchicine in 2023 for patients with established atherosclerotic cardiovascular disease (ASCVD). However, its use was limited for chronic kidney disease (CKD) patients. Reduction in Inflammation in Patients with Advanced Chronic Renal Disease Utilizing Antibody Mediated Interleukin-6 Inhibition (RESCUE) was conducted using Ziltivekimab, an IL-6 ligand monoclonal antibody and found that it significantly reduced high-sensitivity C-reactive protein, an inflammatory surrogate marker. There is an ongoing phase-3 clinical trial, Ziltivekimab Versus Placebo Cardiovascular Outcomes in Participants with Atherosclerotic Cardiovascular Disease, Chronic Kidney Disease, and Systemic Inflammation trial (ZEUS), which will be essential for further anti-inflammation therapy for patients with CKD. Numerous clinical trials have investigated anti-inflammation therapies. Colchicine is by far the only one that has the potential to be widely used due to its cost-effectiveness. Further research is needed on other novel anti-inflammation therapies and their real-world implementation.
在过去十年中，炎症一直被认为是动脉粥样硬化病理生理学的一部分，与脂质堆积并存。然而，一些接受优化降脂治疗的患者炎症生物标志物仍处于升高状态。为此研发了抗炎疗法以消除这种残余风险。我们总结了主要的炎症途径以及抗炎疗法的近期临床试验情况。
秋水仙碱心血管结局试验（COLCOT）和LoDoCo2（秋水仙碱降低慢性冠状动脉疾病主要心血管事件风险）研究发现，低剂量秋水仙碱可分别显著降低近期30天内发生心肌梗死的患者以及慢性冠状动脉疾病患者的心血管死亡、心肌梗死（MI）、缺血性中风和冠状动脉血运重建风险。2023年，美国食品药品监督管理局批准低剂量秋水仙碱用于已确诊的动脉粥样硬化性心血管疾病（ASCVD）患者。然而，其在慢性肾脏病（CKD）患者中的应用有限。利用抗体介导的白细胞介素-6抑制作用降低晚期慢性肾病患者炎症（RESCUE）试验使用IL-6配体单克隆抗体泽尔替库单抗进行研究，发现它可显著降低炎症替代标志物高敏C反应蛋白水平。目前正在进行一项3期临床试验，即泽尔替库单抗对比安慰剂用于动脉粥样硬化性心血管疾病、慢性肾脏病和全身炎症参与者的心血管结局试验（ZEUS），这对于进一步为CKD患者开展抗炎治疗至关重要。众多临床试验对抗炎疗法进行了研究。秋水仙碱因其性价比高，是目前唯一有潜力被广泛应用的药物。其他新型抗炎疗法及其在现实世界中的应用还需要进一步研究。
