Colchicine in Acute Coronary Syndromes: A Meta-Analysis of 12,602 Patients

Inflammation is a leading cause of ischaemic heart disease. Aim of the present study is to assess whether treatment with colchicine in patients with ACS is associated with improved cardiovascular outcomes. We conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) of patients with acute or recent ACS and treated with colchicine versus placebo. PubMed, Scopus, and the Cochrane Central Register of Controlled Trials databases were searched. The primary endpoint was composite of cardiovascular death, recurrent myocardial infarction (MI), stroke or urgent/unplanned revascularization. Other endpoints were individual components of the primary endpoint, all-cause death, non-cardiovascular death, and diarrhea. PROSPERO ID CRD42025648254. Three RCTs were included, involving 12,602 patients. There was no significant difference in the primary composite endpoint between the colchicine and placebo groups (OR 0.82, 95% CI 0.63-1.07, P=0.15). Analysis of individual components of the primary endpoint also revealed no significant differences between the colchicine vs. placebo groups: cardiovascular deaths (P=0.89), recurrent MI (P=0.17), strokes (P=0.27), urgent/unplanned revascularizations (P=0.14), all-cause death (P=0.95), non-cardiovascular death (P=0.98), and diarrhea (P=0.08). At the leave-one-out analysis, the exclusion of the CLEAR trial resulted in a significant reduction in primary endpoint (P=0.005). At further sensitivity analyses, the exclusion of patients who did not receive an initial twice-daily dose regimen and the exclusion of patients enrolled after COVID-19 pandemic resulted in a significant reduction in MACE (P=0.01 and P=0.001, respectively), reflecting heterogeneity among studies. The present meta-analysis raises new questions over the indication, timing and dosing of colchicine in patients with recent MI.