Long-term colchicine therapy in acute coronary syndromes: a systematic review and meta-analysis of randomized controlled trials

Anti-inflammatory therapy, particularly colchicine, has emerged as a potential secondary prevention strategy post-acute coronary syndrome (ACS). This meta-analysis assessed the impact of long-term colchicine therapy (≥12 months) compared to standard care on cardiovascular events in post-ACS patients. A systematic search of PubMed, Cochrane, Scopus, and Web of Science was conducted on December 22, 2024, for randomized controlled trials (RCTs) comparing long-term (≥12 months) treatment with colchicine to standard care in ACS patients. Outcomes assessed included all-cause mortality, cardiovascular death, myocardial infarction (MI), ischemia-driven revascularization, and stroke. Three RCTs (COLCOT, COPS, and CLEAR SYNERGY) with 12,602 patients were included. Colchicine did not significantly reduce all-cause mortality [hazard ratio (HR) 1.01, 95% confidence interval (CI): 0.67-1.53; I²=54%], cardiovascular death (HR 1.01, 95% CI: 0.80-1.29; I²=0%), or MI (HR 0.86, 95% CI: 0.71-1.05; I²=0%). Ischemia-driven revascularization (HR 0.61, 95% CI: 0.30-1.21; I²=81%) and stroke (HR 0.55, 95% CI: 0.18-1.64; I²=75%) showed non-significant reductions with high heterogeneity. The composite outcome of cardiovascular death, MI, revascularization, or stroke was not significantly reduced (HR 0.80, 95% CI: 0.59-1.07; I²=73%). These findings suggest that long-term colchicine therapy did not confer a consistent reduction in major cardiovascular outcomes after ACS. The pooled results indicate an overall null effect; however, the substantial heterogeneity across trials limits the certainty of this conclusion. This analysis may prompt a reassessment of colchicine’s preventive role in ACS. Future studies should aim to reduce heterogeneity through standardized protocols and follow-up reporting and to explore whether subgroups, such as patients with elevated inflammatory markers, may derive benefit.