Low dose vs. higher doses of colchicine for secondary prevention of ischemic stroke and cardiovascular disease. an updated grouped meta-analysis of landmark trials

Introduction: The role of colchicine in secondary cardiovascular prevention remains unclear and debatable when it comes to optimal dosing strategies and patient selection. We conducted a systematic review and meta-analysis comparing low-dose versus higher-dose colchicine for secondary prevention of ischemic stroke and adverse cardiovascular events.

Methods: We searched multiple scientific databases until February 20th, 2025 for randomized controlled trials comparing colchicine with placebo in patients with previous history of ischemic stroke, cardiovascular disease or cardiovascular events. Primary outcome was ischemic stroke incidence; secondary outcomes included adverse cardiovascular events (ACE), myocardial infarction (MI), and mortality. We performed subgroup analyses based on dosing (≤0.5 mg/day vs >0.5 mg/day), age, gender predominance, and trial sample size. Quality assessment used GRADE framework and Cochrane Risk of Bias 2 tool.

Results: Sixteen trials (n=24,967) were included. Low-dose colchicine significantly reduced ischemic stroke risk (RR 0.74, 95% CI 0.59-0.92, p-value= 0.007), especially in younger patients (younger than 65 years-old; RR 0.36, 95% CI 0.17-0.78, p-value= 0.009). Colchicine significantly reduced ACE (RR 0.72, 95% CI 0.65-0.80, p-value<0.001) and MI (RR 0.79, 95% CI 0.66-0.95, p-value= 0.010), with greater benefits observed with low-dose regimens and single daily dosing. Mortality outcomes showed no statistically significant differences.

Conclusions: Low-dose colchicine (0.5 mg daily) appears superior to higher doses for secondary stroke and cardiovascular events prevention. The significant reduction in cardiovascular events, coupled with neutral mortality effects, supports its use as adjunct therapy in selected patients for secondary prevention.

Dr. Reem Mohammed Alsheikh, Assistant Professor in King Saud University for Health Science, Consultant Family Medicine in National Guard Primary Health care center, kn Jeddah, Saudi Arabia. I have a clinical experience for more than twenty years, trainer for residency program for sixteen years, I am currently Residency Program Director of Family Medicine program for Western Region, National Guard.