Abstract Body (Do not enter title and authors here): Background: Stroke is the leading cause of neurological disability worldwide and contributes substantially to mortality. Colchicine is a microtubule inhibitor that has anti-inflammatory properties. In recent years, colchicine has been investigated as a potential therapeutic agent for reducing the risk of adverse cardiovascular events. Few studies have reported the risks of stroke with colchicine, with controversial results to date.

Aim: This meta-analysis aimed to compare the efficacy of colchicine versus placebo for stroke prevention.

Methods: We conducted a comprehensive systematic search of the major databases from inception until May 3, 2024, to identify randomized controlled trials (RCTs) comparing colchicine to placebo. Risk ratios (RR) with 95% confidence intervals (CI) were pooled using an inverse-variance random-effects model. Statistical significance was set at p < 0.05.

Results: We included 13 RCTs with 13629 patients (6823: Colchicine and 6806: Placebo). The mean age in the Colchicine group was 62.1 ± 9.4 years and in the placebo group was 62.4 ± 9.1 years. Colchicine was associated with a significantly lower risk of stroke [RR: 0.51; 95% CI: -0.32, 0.80; p=0.003] than placebo. However, the risk of all-cause mortality [RR: 1.01; 95% CI: 0.66, 1.54; p=0.97] was similar between the two groups.

Conclusion: This study demonstrated the efficacy of colchicine in reducing the risk of stroke. However, colchicine did not reduce the risk of all-cause mortality. Future RCTs are required to investigate this risk reduction on a larger, multicenter scale.