Combining Colchicine and Antiplatelet Therapy to Tackle Atherothrombosis: A Paradigm in Transition?

Abstract

Atherothrombosis, the primary driver of acute cardiovascular (CV) events, is characterized by the activation of three key pathophysiological pathways: platelets, coagulation, and inflammation. Dual antiplatelet therapy (DAPT) is the current standard of care for patients with acute coronary syndrome, providing significant reductions in cardiovascular (CV) events, albeit with an associated increased risk of bleeding. However, the high residual risk of recurrent events among these patients highlights the need for alternative strategies to treat and prevent atherothrombosis. To this extent, several approaches aimed at targeting atherothrombosis have been proposed. Among these, a strategy of dual-pathway inhibition simultaneously targeting platelets, using single or DAPT, and coagulation, using a low-dose anticoagulant such as rivaroxaban 2.5 mg twice daily, has shown to reduce CV events but at the expense of increased bleeding. Targeting inflammatory pathways has the potential to be a highly effective strategy to tackle atherothrombosis without increasing bleeding risk. Several anti-inflammatory agents have been tested in patients with coronary artery disease, but to date only colchicine is approved for secondary prevention on top of standard care, including antiplatelet therapy. However, many aspects of colchicine's mechanism of action, including its antiplatelet effects and how it synergizes with antiplatelet therapy, remain unclear. In this review, we summarize the available clinical and pre-clinical evidence on the antiplatelet effects of colchicine and its synergistic interactions with antiplatelet therapy, highlighting their potential role in addressing atherothrombosis.

Keywords: antiplatelet; atherothrombosis; colchicine; inflammation; thrombo-inflammation.

Figure 1

Strategies for Tackling Atherothrombosis in Patients with Atherosclerotic Cardiovascular Disease. Emerging evidence underscores the complex interplay between platelets, coagulation, and inflammation in the development of thrombus formation and atherothrombosis. Current therapeutic strategies aim to reduce cardiovascular events by disrupting these pathways that are responsible for atherogenesis and atherothrombosis. Dual antiplatelet therapy, combining aspirin and a P2Y₁₂ inhibitor, primarily targets platelet reactivity to prevent thrombotic complications. A more comprehensive approach involves the simultaneous inhibition of platelets and coagulation using aspirin or a P2Y₁₂ inhibitor in combination with low-dose rivaroxaban (2.5 mg twice daily). However, because both platelets and coagulation factors are integral to normal hemostasis, these therapies reduce thrombotic events but at the expense of increased risk of bleeding. An alternative approach focuses on combining aspirin or a P2Y₁₂ inhibitor with colchicine to target both platelet activity and inflammatory pathways. By addressing inflammation, a key driver of atherothrombosis, this strategy has the potential to reduce thrombotic risk while minimizing the bleeding complications typically associated with intense antithrombotic therapies. Abbreviations: ASA: aspirin, P2Y12i: P2Y₁₂ inhibitors; Riva: rivaroxaban.