Biotherapeutics Translational Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea.
Immune and Vascular Cell Network Research Center, National Creative Initiatives, Department of Life Sciences, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul, 120-750, Republic of Korea.
Arch Pharm Res. 2019 Mar;42(3):206-223. doi: 10.1007/s12272-019-01116-1. Epub 2019 Feb 6.
Despite the introduction of statins for lowering LDL-C level, atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of death and morbidity worldwide. Combination therapies with statin and other lipid-lowering drugs, including ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, have unlocked additive benefits for treatment of ASCVD, but morbidity and mortality due to ASCVD remain high. New anti-inflammatory therapies have emerged for treatment and prevention of ASCVD to address these problems. Canakinumab neutralization of interleukin-1β (IL-1β) is the only verified therapy, and low-dose methotrexate holds promise due to its efficacy and safety for treatment of ASCVD. However, many agonistic and antagonistic candidates within inflammation pathways have failed to develop into useful drugs for ASCVD because of the complexity of the inflammatory process in atherosclerosis. In this review, we outline current and future pharmaceutical therapies for ASCVD in terms of lipid-modifying strategies and anti-inflammation treatments.
尽管已引入他汀类药物来降低 LDL-C 水平,但动脉粥样硬化性心血管疾病(ASCVD)仍然是全球范围内导致死亡和发病的主要原因。他汀类药物与其他降脂药物(包括依折麦布和前蛋白转化酶枯草溶菌素 9(PCSK9)抑制剂)的联合治疗为 ASCVD 的治疗带来了额外的益处,但 ASCVD 导致的发病率和死亡率仍然很高。为了解决这些问题,已经出现了新的抗炎治疗方法来治疗和预防 ASCVD。白细胞介素-1β(IL-1β)的中和抗体坎那奴单抗是唯一经过验证的疗法,而低剂量甲氨蝶呤因其治疗 ASCVD 的疗效和安全性而具有潜力。然而,由于动脉粥样硬化中炎症过程的复杂性,炎症途径中的许多激动剂和拮抗剂候选药物都未能开发成为治疗 ASCVD 的有用药物。在本文中,我们根据调脂策略和抗炎治疗,概述了目前和未来用于 ASCVD 的药物治疗方法。