The efficacy and safety of low dose colchicine in atherosclerotic cardiovascular disease: a systematic review and meta-analysis

AIMS: Colchicine has recently been approved for the treatment of atherosclerotic cardiovascular disease (ASCVD). Since then, three large trials of colchicine in ASCVD have failed to reach their primary endpoints. METHODS AND RESULTS: A systematic search of PubMed, Embase and Cochrane Central Register of Controlled Trials was performed (PROSPERO registration: CRD42024616378). The primary endpoint of major adverse cardiovascular events (MACE) was defined as a composite of myocardial infarction (MI), stroke and cardiovascular death. The key secondary endpoint of extended MACE (eMACE) was defined as MACE plus coronary revascularisation. Pooled estimates were calculated using a random-effects model and are presented as risk ratio [95% confidence interval (CI)]. 1624 articles were screened. 12 met inclusion criteria, yet one trial reported zero endpoint events in both arms. As such, 11 trials were included in the meta-analysis, with a total of 1983 primary endpoint events across 30 808 participants. Colchicine was associated with a 17% reduction in the incidence of MACE [0.83 (0.73, 0.95); P = 0.006] and 23% reduction in the incidence of eMACE [0.77 (0.63, 0.94); P = 0.01]. This reduction was driven by a lower rate of MI [0.78 (0.63, 0.95); P = 0.02] and coronary revascularisation [0.73 (0.55, 0.97); P = 0.03]. There were also numerically fewer strokes in the colchicine-treated population [0.81 (0.63, 1.04); P = 0.11]. Colchicine had no effect on cardiovascular [0.96 (0.79, 1.15); P = 0.64] or non-cardiovascular mortality [1.04 (0.76, 1.41); P = 0.81]. CONCLUSION: Colchicine reduces the risk of non-fatal ischaemic events in patients with ASCVD. Further studies are required to identify a population(s) who stands to benefit most from this promising therapy.