Dipartimento Di Scienze Cardiovascolari E Toraciche, Fondazione Policlinico A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Largo A.Gemelli 8, Rome, 00168, Italy.
Università Cattolica del Sacro Cuore, Rome, 00168, Italy.
Clin Res Cardiol. 2021 Oct;110(10):1531-1542. doi: 10.1007/s00392-021-01828-9. Epub 2021 Mar 13.
Inflammation is the main pathophysiological process involved in atherosclerotic plaque formation, progression, instability, and healing during the evolution of coronary artery disease (CAD). The use of colchicine, a drug used for decades in non-ischemic cardiovascular (CV) diseases and/or systemic inflammatory conditions, stimulated new perspectives on its potential application in patients with CAD. Previous mechanistic and preclinical studies revealed anti-inflammatory and immunomodulatory effects of colchicine exerted through its principal mechanism of microtubule polymerization inhibition, however, other pleiotropic effects beneficial to the CV system were observed such as inhibition of platelet aggregation and suppression of endothelial proliferation. In randomized double-blinded clinical trials informing our clinical practice, low doses of colchicine were associated with the significant reduction of cardiovascular events in patients with stable CAD and chronic coronary syndrome (CCS) while in patients with a recent acute coronary syndrome (ACS), early initiation of colchicine treatment significantly reduced major adverse CV events (MACE). On the other hand, the safety profile of colchicine and its potential causal relationship to the observed increase in non-CV deaths warrants further investigation. For these reasons, postulates of precision medicine and patient-tailored approach with regards to benefits and harms of colchicine treatment should be employed at all times due to potential toxicity of colchicine as well as the currently unresolved signal of harm concerning non-CV mortality. The main goal of this review is to provide a balanced, critical, and comprehensive evaluation of currently available evidence with respect to colchicine use in the setting of CAD.
炎症是动脉粥样硬化斑块形成、进展、不稳定和愈合的主要病理生理过程,也是冠心病(CAD)演变过程中的主要病理生理过程。秋水仙碱是一种几十年来用于非缺血性心血管(CV)疾病和/或全身性炎症性疾病的药物,其在 CAD 患者中的潜在应用激发了新的研究视角。先前的机制和临床前研究揭示了秋水仙碱通过抑制微管聚合的主要机制发挥抗炎和免疫调节作用,然而,也观察到了其他有益于心血管系统的多效作用,如抑制血小板聚集和抑制内皮细胞增殖。在为我们的临床实践提供信息的随机双盲临床试验中,低剂量秋水仙碱与稳定型 CAD 和慢性冠状动脉综合征(CCS)患者心血管事件的显著减少相关,而在近期急性冠状动脉综合征(ACS)患者中,早期开始秋水仙碱治疗可显著降低主要不良心血管事件(MACE)。另一方面,秋水仙碱的安全性特征及其与非心血管死亡观察到的增加的潜在因果关系需要进一步研究。由于秋水仙碱的潜在毒性以及目前尚未解决的非心血管死亡率信号,因此,应始终采用精准医学和针对患者的治疗方法,权衡利弊。本综述的主要目的是对 CAD 患者中使用秋水仙碱的现有证据进行平衡、批判性和全面的评估。