Effect of Low Dose of Colchicine on Platelet Reactivty in Patients With Chronic Coronary Disease

Inflammation plays an important role in atherosclerosis and the occurrence of ischemic events. Statins, in addition to their lipid-lowering effect, have also documented an anti-inflammatory effect that may partly explain their clinical benefit in reducing cardiovascular ischemic events. More recently, canaquinumab, a monoclonal anti-interleukin 1β antibody, significantly reduced vascular events in patients after acute myocardial infarction with residual inflammation, but failed to demonstrate progression to diabetes, including in patients with pre-diabetes. On the other hand, methotrexate has not been shown to be effective in reducing events in a similar population.

In addition to inflammation, thrombosis is directly involved in the pathogenesis of unstable ischemic syndromes. In this context, the association between greater platelet aggregability and clinical events is well established in the literature. The POPULAR study evaluated that after a 1-year follow-up, the primary outcome of death, non-fatal acute myocardial infarction, stent thrombosis or ischemic stroke occurred more frequently in patients with high platelet reactivity undergoing treatment with antiaggregants when evaluated by optical aggregometry and other point of care tests. Another study that evaluated the importance of the platelet response to medications was the ADAPT-DES, in which post-angioplasty patients on dual antiplatelet therapy were at higher risk of complications, especially stent thrombosis, when they presented with high platelet reactivity to clopidogrel. Both studies show the importance of the interaction between platelet changes and the medications that interact in this way and cardiovascular outcomes.

Colchicine is an orally administered anti-inflammatory drug that was initially extracted from autumn saffron and has been used for centuries in various diseases of an anti-inflammatory / autoimmune nature. Its bioavailability after oral administration takes place via uptake in the jejunum and ileum, its lipophilic nature allows it to be absorbed quickly by various types of cells. Its mechanism of action occurs through the inhibition of tubulin polymerization and the generation of microtubules and, possibly, effects on cell adhesion molecules and inflammatory chemokines.

Another route related to colchicine is the suppression of interleukin 1. It is able to prevent the intracellular assembly of the cytosolic protein complex NACHT-LRRPYD 3, responsible for the proteolytic cleavage of caspase-1, which breaks down and activates interleukin 1, blocking its maturation and secretion.

In addition to the action on inflammation, colchicine may be involved in reducing platelet aggregation, as suggested in a mechanistic study that evaluated the in vitro action of colchicine on platelet aggregation in healthy individuals. In this study, in addition to demonstrating the lower aggregability by electrical impedance in the sample subjected to colchicine action, it was found that the drug also exerted effects via inhibition of key proteins involved in the rearrangement of the platelet cytoskeleton. To the best of our knowledge, however, there are no studies evaluating the in vivo "antiplatelet action" of colchicine in patients with established cardiovascular disease.