This meta-analysis included the totality of RCTs comparing clinical outcomes of colchicine versus placebo in patients with ACS. Our analysis demonstrated that colchicine may reduce the primary outcome of MACE compared with placebo. However, this outcome was limited by marginal statistical significance and high heterogeneity. In addition, excluding the study with a higher risk of bias (Akrami et al.) and a subgroup analysis including studies with similar MACE definitions showed no difference in MACE between colchicine and placebo which raises uncertainty regarding the true benefit of colchicine in the reduction of MACE. Although the study by Akrami et al. was included in the overall pooled analysis to provide a comprehensive synthesis of the available RCT evidence, it substantially influenced the overall results, as the observed modest benefit appears to be largely driven by this single high-risk trial.

Furthermore, colchicine did not reduce individual outcomes of MACE, including all-cause mortality, cardiac mortality, MI, ischemia-driven repeat revascularization, and stroke. The marginal reduction of MACE could be attributed to increased statistical power from pooling individual outcomes. However, inconsistent MACE definitions across trials led to high heterogeneity. Sensitivity analysis excluding the study with a higher risk of bias showed no reduction in MACE, with a marked reduction of heterogeneity (I2 = 35%). Additionally, there were no differences in CRP levels, all-adverse events or serious adverse events between both groups. However, colchicine was associated with a higher risk of GI side effects. Although colchicine is an anti-inflammatory drug, the lack of CRP reduction in our study suggests limited anti-inflammatory efficacy in ACS, which may explain the absence of clear clinical benefits. These findings call into question the benefits of routine use of colchicine after ACS.

Prior meta-analyses have shown mixed results regarding the role of colchicine in patients with coronary artery disease (CAD). A previous meta-analysis by Ullah et al., which included patients with stable CAD and ACS, showed that colchicine reduced the risk of MACE, ACS, ischemic stroke, and the need for revascularization [8]. Another meta-analysis by Ma et al. which included acute and chronic CAD, demonstrated a reduction in MACE, stroke, MI, and risk of revascularization but showed no reduction in cardiovascular death or all-cause mortality [9]. A meta-analysis by Razavi et al. that involved patients with ACS demonstrated that colchicine did not show difference in the incidence of MI or the composite endpoint of MI or all-cause mortality but showed a reduction in the incidence of stroke [10]. Our meta-analysis included recent RCTs of 12,979 patients and focused solely on patients with ACS. Our study demonstrated that colchicine may be associated with only a marginal reduction in MACE, with no benefit in individual outcomes.

This meta-analysis has few limitations. First, there was a high degree of heterogeneity among the included trials, particularly in the primary outcome, which may have influenced the pooled estimates showing a modest and marginally significant reduction in MACE in the primary analysis. So, we conducted a sensitivity analysis excluding the study with a higher risk of bias, which mitigated the heterogeneity and eliminated the statistical significance of the association. Second, the analysis was based on study-level data rather than patient-level data, which limited the ability to perform more granular analyses. Third, publication bias, although not detected in the funnel plot inspection, cannot be completely ruled out, given the limited number of studies available. Finally, the adherence and drug discontinuation rates have varied among the included studies, which may have affected the treatment efficacy and safety outcomes.