Effects of Colchicine on Cardiovascular Outcomes in Patients with Coronary Artery Disease: A Systematic Review and One-Stage and Two-Stage Meta-Analysis of Randomized-Controlled Trials.

Aim Colchicine has received emerging interest due to its cardiovascular benefits in patients with coronary artery disease (CAD). We conducted a one-stage meta-analysis of reconstructed individual patient data (IPD) from randomized-controlled trials to summarize the effects of colchicine on cardiovascular outcomes in patients with CAD. Methods Four databases (PubMed, Embase, Cochrane, SCOPUS) were searched for articles published from inception to 30th September 2020, examining the effect of colchicine on cardiovascular outcomes in patients with CAD, yielding 10 randomized-controlled trials with a combined cohort of 12,781 patients. IPD was reconstructed from Kaplan-Meier curves published in 3 studies and analysed using the shared-frailty Cox model. Aggregate data meta-analysis of all 10 studies was performed for outcomes unsuitable for IPD reconstruction. Results In patients receiving colchicine compared to placebo, one-stage meta-analysis demonstrated a hazard ratio of 0.70 (95% CI 0.61-0.80) for the composite outcome of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and urgent hospitalization for angina requiring coronary revascularization. Aggregate data meta-analysis demonstrated a significant reduction in hazard rate for stroke (HR 0.45; 95% CI 0.27-0.75) and urgent revascularization (HR 0.59; 95% CI 0.38-0.91); and a relative risk reduction for myocardial infarction (RR 0.72; 95% CI of 0.52-1.00) and post-operative atrial fibrillation (RR 0.64; 95% CI 0.48-0.86). Conclusion Given the significant benefits of colchicine demonstrated on IPD, and its consistent benefits when analyzed using aggregate data meta-analysis, we propose that colchicine may be considered as an additional pharmacological adjunct to the first line therapy for patients with coronary artery disease.