Colchicine in Cardiovascular Disease: In-Depth Review

Abstract

Inflammation plays a prominent role in the development of atherosclerosis and other cardiovascular diseases, and anti-inflammatory agents may improve cardiovascular outcomes. For years, colchicine has been used as a safe and well-tolerated agent in diseases such as gout and familial Mediterranean fever. The widely available therapeutic has several anti-inflammatory effects, however, that have proven effective in a broad spectrum of cardiovascular diseases as well. It is considered standard-of-care therapy for pericarditis, and several clinical trials have evaluated its role in postoperative and postablation atrial fibrillation, postpericardiotomy syndrome, coronary artery disease, percutaneous coronary interventions, and cerebrovascular disease. We aim to summarize colchicine's pharmacodynamics and the mechanism behind its anti-inflammatory effect, outline thus far accumulated evidence on treatment with colchicine in cardiovascular disease, and present ongoing randomized clinical trials. We also emphasize real-world clinical implications that should be considered on the basis of the merits and limitations of completed trials. Altogether, colchicine's simplicity, low cost, and effectiveness may provide an important addition to other standard cardiovascular therapies. Ongoing studies will address complementary questions pertaining to the use of low-dose colchicine for the treatment of cardiovascular disease.

Keywords: atrial fibrillation; cerebrovascular; colchicine; coronary artery disease; disorders; inflammation; percutaneous coronary intervention; pericarditis; postpericardiotomy syndrome.

Figure 1.. Inflammation in cardiovascular disease and anti-inflammatory targets of colchicine and canakinumab.

Colchicine has broad anti-inflammatory effects, here illustrated here in atherosclerosis. Colchicine inhibits (1) neutrophil migration, adhesion, activation, (2), neutrophil release of defensins, MMP, and elastin, (3) NLRP3 activation of the inflammatory pathway with release of IL-1β, in turn activating IL-6, and eventually stimulation CRP, and (4) smooth muscle proliferation and vascular stenosis. (5) Canakinumab is a monoclonal antibody that specifically targets the upstream inflammatory mediator IL-1β. CRP = C-reactive protein; IL = Interleukin; MMP = Matrix Metalloproteinases, NLRP3 = NLR Family Pyrin Domain Containing 3, TGF = transforming growth factor

Figure 2.. Various CYP-3A4- and P-glycoprotein inhibitors that effect colchicine metabolism.

CYP-3A4- and P-glycoprotein inhibitors may alter the liver and kidney’s ability to clear colchicine. Concomitant administration of strong inhibitors with colchicine should generally be avoided, while moderate/mild inhibitors may cautiously be used with colchicine through dose reductions and shared decision making. P-gp = P-glycoprotein. Figure designed with BioRender.