Colchicine for the prevention of ischemic stroke: An updated meta-analysis of randomized clinical trials

BACKGROUND: Inflammation is increasingly recognized as a target to reduce residual cardiovascular risk. Colchicine is an anti-inflammatory drug that was associated with improved cardiovascular outcomes. However, its effect on stroke reduction was not consistent across studies. Therefore, the aim of this study-level meta-analysis was to evaluate the influence of colchicine on stroke in patients with coronary artery disease (CAD). METHODS: Electronic databases were searched through October 2020, to identify randomized controlled trials using colchicine in patients with CAD. The incidence of clinical endpoints such as stroke, death, myocardial infarction (MI), study-defined major adverse cardiovascular events (MACE), and atrial fibrillation (AF) was compared between colchicine and placebo groups. RESULTS: A total number of 11,594 (5,806 in the colchicine arm) patients from 4 eligible studies were included in the final analysis. Stroke incidence was lower in the colchicine arm compared to placebo (rate ratio [RR] 0.48 [95% confidence interval [CI], 0.29–0.78], P = 0.003) whereby no significant difference was observed in the incidence of AF (odds ratio [OR] 0.86 [95% CI, 0.69–1.06], P = 0.16). Furthermore, a significant effect of colchicine on MACE [RR 0.65 (95% CI, 0.51–0.83), P = 0.0006] and MI (RR 0.65 (95% CI, 0.54–0.95], P = 0.02) was detected, with no influence on all-cause mortality (RR 1.04 [95% CI, 0.61–1.78], P = 0.88). CONCLUSIONS: This meta-analysis confirms a significant influence of colchicine on stroke in CAD patients. Despite its neutral effect on AF occurrence, other mechanisms related to plaque stabilization are plausible. The concept seems to be supported by contemporaneous MI reduction and posits that anti-inflammatory properties of colchicine may translate into a reduction of stroke risk.