Objective:

To provide an updated aggregation of RCT evidence supporting colchicine for stroke prevention.

Background:

Based on randomized control trials showing cardiovascular benefits, including primary stroke prevention, FDA approved low dose colchicine in June 2023 to reduce risk of stroke, myocardial infarction, coronary revascularization, and cardiovascular death in patients with established atherosclerotic disease or multiple risk cardiovascular risk factors. A systematic review of RCT stroke outcomes including most recent extended follow-up data has not been reported.  

Design/Methods:

We performed a formal literature search for RCTs of long-term colchicine use in patients with atherosclerosis indications published from 2000-2023 and study-level meta-analysis using RevMan software. Outcomes analyzed were: stroke; MI; coronary revascularization; cardiovascular/all-cause mortality; and combined major adverse cardiovascular events (MACE). Heterogeneity was assessed with the I2 statistic and interaction p values and potential bias assessed with the Risk of Bias 3.0 scale.

Results:

Four RCTs met selection criteria, enrolling 11,285 patients (5626 colchicine, 5659 placebo), with median follow-up of 23.3 months. Long-term colchicine doses in all trials was 0.5 mg once-daily. Colchicine treatment produced a 50% relative risk reduction in stroke (0.43% vs 0.88%, risk ratio (RR)=0.50, 95%CI: 0.31-0.82; p=0.006). Colchicine also produced reductions in MI (3.22% vs 4.15%), RR=0.78, 95%CI: 0.65-0.95; p=0.01); coronary revascularization (RR=0.73, 95%CI: 0.59-0.91; p= 0.004); and MACE (RR=0.71, 95% confidence interval: 0.59-0.85; p<0.00001). However, colchicine had non-significant effect on risk of all-cause mortality (RR: 1.17; 95%Cl: 0.91-1.51, p=0.21) and CV death (RR: 0.90; 95%Cl: 0.60-1.34, p=0.60). No substantial heterogeneity across trials was noted (I2 values 0%). In sensitivity analysis, adding the one long-term trial in COVID-19 patients did not alter study findings. 

Conclusions:

Low-dose colchicine treatment decreases stroke risk and myocardial infarction in patients with a history of atherosclerotic cardiovascular disease or CV risk factors. Among every 1000 patients treated over 5 years, 11 strokes and 22 MIs are avoided.