The Role of Colchicine in Atherosclerotic Cardiovascular Disease.

Colchicine, an inexpensive immunomodulatory drug used traditionally to treat gout and familial Mediterranean fever, is rapidly accumulating basic and clinical evidence for a therapeutic role in atherosclerotic cardiovascular disease. Its athero-protective properties are thought to be mainly related to its effect on tubulin polymerisation, enabling a broad range of effect on multiple atherosclerotic plaque cell types and cellular processes, including cell division, cell migration as well as pro-inflammatory cytokine and chemokine secretion. These properties indicate the potential to favourably affect all stages of atherosclerotic plaque development including formation, progression, destabilisation, and plaque rupture. This review focusses on the pharmacology of colchicine, the mechanisms by which it modulates atherosclerosis pathobiology, and summarises the current clinical evidence for its use along with the upcoming clinical trial landscape. Given the current lack of primary immunomodulatory drugs in the treatment of atherosclerosis, colchicine is a promising candidate to fill this therapeutic gap.

Kurup R ，Galougahi KK ，Figtree G ，Misra A ，Patel S ... -  《-》

The Beneficial Therapy with Colchicine for Atherosclerosis via Anti-inflammation and Decrease in Hypertriglyceridemia.

Lipid-lowering therapy and control of cardiovascular risk factors are the current recommendations of atherosclerotic disease management. Despite optimal treatment the rate of acute coronary syndrome events remains high. Inflammation plays an essential role in the pathophysiology of atherosclerotic plaque formation, progression and rupture, which conclusively causes acute clinical episodes. This review aims to give a conceptual description of the potential therapeutic benefits and effects of colchicine in inflammation-mediated atherosclerotic disease and hypertriglyceridemia. A complete literature survey was performed using the PubMed database search to collect available information regarding colchicine, atherosclerosis, and hypertriglyceridemia. A total of 42 studies met the selection criteria for inclusion in the review. Inflammation is a well-known key mediator of atherogenesis in coronary artery disease. Colchicine has direct antiinflammatory effects by inhibiting critical inflammatory signaling networks as the inflammasome, pro-inflammatory cytokines, and expression of adhesion molecules, preventing both local chemoattraction of inflammatory cells such as neutrophils and systemic inflammation including the decrease of the release of IL-1β by the neutrophils. Colchicine reduces the levels of inflammatory markers, stabilizes the coronary plaque, leads to more favorable cardiac healing after damage, and reduces the acute coronary syndromes event recurrence. Colchicine reduces the myocardial infarct size, myocardial fibrosis, and improves the hemodynamic parameters. Several studies report the potential attenuating role of colchicine on triglyceride levels. Current evidence though regarding the pathophysiological mechanism of colchicine's triglyceride-lowering effect remains scarce.

Spartalis M ，Spartalis E ，Tzatzaki E ，Tsilimigras DI ，Moris D ，Kontogiannis C ，Kaminiotis VV ，Paschou SA ，Chatzidou S ，Siasos G ，Voudris V ，Iliopoulos DC ... -  《-》

Colchicine in Stable Coronary Artery Disease.

Disease management of stable coronary artery disease consists of controlling hemostasis and lipid regulation. No treatment strategies preventing plaque erosion or rupture are yet available. Cholesterol crystal-induced inflammation leading to plaque destabilization is believed to be an important factor contributing to plaque instability and might well be amenable to treatment with anti-inflammatory drugs. Colchicine has anti-inflammatory properties with the potential to address both the direct and indirect inflammatory mechanisms in the plaque. A literature search was performed in MEDLINE (PubMed), EMBASE, and the Cochrane Central Register of Controlled Trials, as well as in the clinical trial registries, to identify finished and ongoing clinical studies on colchicine in stable coronary artery disease. Preclinical findings of colchicine in stable coronary artery disease have shown protective effects on surrogate outcomes, such as myocardial infarction size and postangioplasty restenosis. Retrospective cohort studies in patients with gout report a lower incidence of combined cardiovascular outcomes in those treated with colchicine. Thus far, one prospective, randomized clinical trial has provided evidence on a possible protective effect of colchicine in stable coronary artery disease. Meta-analysis of trials of colchicine in multiple cardiovascular diseases revealed a decrease in myocardial infarction with varying levels of evidence. Currently, 5 major clinical trials involving >10,000 patients are recruiting patients, all focusing on major cardiovascular outcomes. The body and quality of evidence regarding the efficacy of colchicine for secondary prevention of stable and acute phases of coronary artery disease will be greatly expanded in the upcoming years, providing less biased and more accurate effect estimates. If colchicine's anti-inflammatory characteristics translate to improved event-free cardiovascular survival, this relatively safe, low-cost, and well-known drug may become the third pillar (next to lipid regulation and platelet inhibition) in the medical management of stable coronary artery disease.

Fiolet ATL ，Nidorf SM ，Mosterd A ，Cornel JH ... -  《-》

The Role of Colchicine in Coronary Artery Disease.

There is increasing experimental and clinical evidence that inflammation appears to play an important role in atherosclerosis and coronary artery disease. Treatment of coronary artery disease currently involves management of cardiovascular risk factors, lipid-lowering strategies and antiplatelet medications. Inflammation seems to be central to the pathogenesis of atherosclerotic plaque development, instability, and rupture seen in coronary artery disease. Colchicine, a well-known and relatively inexpensive drug, has unique anti-inflammatory properties, which is generating considerable interest in its potential role in reducing cardiovascular morbidity and potentially mortality. This review discusses the mechanism of action of colchicine in preventing and treating atherosclerosis as well as the literature from recent clinical studies supporting its use in coronary artery disease.

Butt AK ，Cave B ，Maturana M ，Towers WF ，Khouzam RN ... -  《-》

Colchicine and plaque: A focus on atherosclerosis imaging.

Colchicine is an anti-inflammatory medication, classically used to treat a wide spectrum of autoimmune diseases. More recently, colchicine has proven itself a key pharmacotherapy in cardiovascular disease (CVD) management, atherosclerotic plaque modification, and coronary artery disease (CAD) treatment. Colchicine acts on many anti-inflammatory pathways, which translates to cardiovascular event reduction, plaque transformation, and plaque reduction. With the FDA's 2023 approval of colchicine for reducing cardiovascular events, a novel clinical pathway opens. This advancement paves the route for CVD management that synergistically merges lipid lowering approaches with inflammation inhibition modalities. This pioneering moment spurs the need for this manuscript's comprehensive review. Hence, this paper synthesizes and surveys colchicine's new role as an atherosclerotic plaque modifier, to provide a framework for physicians in the clinical setting. We aim to improve understanding (and thereby application) of colchicine alongside existing mechanisms for CVD event reduction. This paper examines colchicine's anti-inflammatory mechanism, and reviews large cohort studies that evidence colchicine's blossoming role within CAD management. This paper also outlines imaging modalities for atherosclerotic analysis, reviews colchicine's mechanistic effect upon plaque transformation itself, and synthesizes trials which assess colchicine's nuanced effect upon atherosclerotic transformation.

Aldana-Bitar J ，Golub IS ，Moore J ，Krishnan S ，Verghese D ，Manubolu VS ，Benzing T ，Ichikawa K ，Hamal S ，Kianoush S ，Anderson LR ，Ramirez NR ，Leipsic JA ，Karlsberg RP ，Budoff MJ ... -  《-》