Balancing the benefits and risks of colchicine use among patients with atherosclerotic cardiovascular disease: an umbrella review of meta-analyses of randomised controlled trials

The risks and benefits of colchicine use among patients with atherosclerotic cardiovascular disease (ASCVD) have been widely reported. Our umbrella review aimed to systematically analyse and synthesise the available causal evidence on the therapeutic effects and safety profile of colchicine in patients with ASCVD. We searched PubMed, Embase, Web of Science, and Cochrane Library from database inception to December 4, 2024, to identify systematic reviews and meta-analyses of randomised controlled trials (RCTs) investigating colchicine use among patients with ASCVD. The primary endpoints were physical adverse events, MACEs, and CV disorder. The quality of systematic reviews was evaluated using A Measurement Tool to Assess Systematic Reviews (AMSTAR), and the certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system. Risk of bias was evaluated using Cochrane Systematic Review criteria. Inconsistency was flagged if heterogeneity (I 2 ) exceeded 50%, or 75% without explanation. Publication bias was detected via funnel plot asymmetry or Egger's test. Subgroup analyses were done according to colchicine dose, treatment duration, geographical region, participant age and disease of patients. This study is registered with PROSPERO (CRD 42025631311). This review analysed 47 unique outcomes from 48 systematic reviews and meta-analyses of RCTs. Among 271 associations, 95 were supported by high-certainty evidence. For primary outcomes, compared with placebo treatment, colchicine exhibited therapeutic efficacy in coronary heart disease [relative risk (RR): 0.73, 95% confidence interval (CI): 0.64-0.83, I 2 : 0%] and acute coronary syndromes (OR: 0.72, 95% CI: 0.58-0.89, I 2 : 0%), demonstrating secondary prevention benefits in major adverse cardiovascular events (RR: 0.56, 95% CI: 0.47-0.67, I 2 : 0%). Common adverse effects included gastrointestinal reactions and hepatic toxicity, with dose-dependent associations of drug discontinuation (RR: 4.63, 95% CI: 2.06-10.38, I 2 : 36%). Evidence of publication bias was identified in 18 of 271 tested associations. Subgroup analyses indicated that optimal clinical application required consideration of patient age, geographic variance in pharmacogenomics, and protocol adjustments (recommended dose ≤0.5 mg/day for more than a month) to balance efficacy-risk profiles. High-certainty evidence supported the therapeutic and secondary preventive benefits of colchicine in patients with ASCVD when dose and duration were appropriately controlled. Future studies could focus on identifying ASCVD subgroups with pharmacogenomic and ethnographic predictors of colchicine response heterogeneity to guide precision therapy. This work was supported by the Liaoning Revitalization Talents Program, Outstanding Youth Scientific Talent Project of Dalian, and Outstanding Scientific Fund of Shengjing Hospital.