Low-Dose Colchicine for Secondary Prevention: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Introduction

Inflammation is recognized as a probable causal factor in recurrence of atherosclerotic events, making it a promising therapeutic target.^, Plasma C-reactive protein, a marker of systemic inflammation, has been shown to predict the risk of cardiovascular events regardless of cholesterol and other traditional risk factors.^, In the Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease (CANTOS) trial, inhibition of interleukin-1β demonstrated a reduction in cardiovascular events. Afterwards, colchicine, an inexpensive anti-inflammatory drug, emerged as a promising treatment to target residual inflammatory risk. Its primary mechanism involves inhibiting the NLRP3 inflammasome, which plays a crucial role in atherosclerosis-associated inflammation by producing pro-inflammatory cytokines like interleukin-1β.

The Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction (COLCOT) and the Colchicine in Patients with Chronic Coronary Disease (LoDoCo2) trials demonstrated a reduction in major adverse cardiovascular events (MACE).^, A meta-analysis of these two major trials and several smaller randomized controlled trials (RCTs) concluded that colchicine reduces MACE, myocardial infarction (MI), coronary revascularization, and stroke in secondary prevention, although it did not improve cardiovascular mortality. Consequently, colchicine is now recommended for secondary prevention by European guidelines for managing acute and chronic coronary syndromes and by American guidelines for chronic coronary disease.^–

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