Colchicine in Coronary Artery Disease: Comparative Review of CLEAR SYNERGY, LoDoCo2 and COLCOT

This review examines differences between three large colchicine trials, including study design, trial populations, timing of treatment initiation, colchicine dosing regimens, geographic factors, the timing of trial conduct and inflammatory response.

Colchicine inhibits neutrophil function and affects nucleotide-binding oligomerisation domain-like receptors, pyrin domain-containing 3 (NLRP3) inflammasome activity, thereby reducing the release of downstream pro-inflammatory cytokines such as mature interleukin-1β and interleukin-6. Large randomized controlled trials have evaluated the effects of colchicine in the secondary prevention of coronary artery disease with divergent results. The Colchicine Cardiovascular Outcomes Trial (COLCOT) in patients with recent myocardial infarction (MI) and the Low-Dose Colchicine 2 (LoDoCo2) trial in patients with chronic coronary syndrome showed relative risk reductions of 23% and 31% for major adverse cardiovascular events (MACE). In contrast, the CLEAR SYNERGY trial in patients with recent MI yielded neutral results. Differences between COLCOT, LoDoCo2 and CLEAR SYNERGY provide insights into these aspects of the trials, but do not give definite answers as to why results were divergent. Future detailed analyses of CLEAR SYNERGY, such as stratification by time to treatment initiation, landmark analyses, re-evaluation of events, and assessments of the relationship between inflammatory response and outcomes, could provide additional insights.