Magnitude of effect of low dose colchicine, a newly food and drug administration approved treatment for stroke prevention.

Background: As the Food and Drug Administration in June 2023 approved low dose colchicine for primary prevention of stroke and other cardiovascular events, an updated meta-analysis of stroke outcomes in randomized trials would help inform clinical practice.**** METHODS: Systematic, study-level meta-analysis of randomized clinical trials of long-term colchicine in patients with established atherosclerotic cardiovascular disease (ASCVD, preponderantly primary prevention for stroke) or following non-cardioembolic ischemic stroke/transient ischemic attack (secondary prevention). Heterogeneity was assessed with the I statistic and Cochrane's Q and potential bias assessed with the Risk of Bias 2.0 scale.

Results: Six randomized control trials met selection criteria, enrolling 14,987 patients (7495 colchicine, 7492 placebo), with median follow-up 26.3 months. Colchicine dosage in all trials was 0.5 mg once-daily. Across all trials, colchicine treatment produced a 28 % relative risk reduction in stroke (1.77 % vs 2.54 %, risk ratio (RR)=0.72, 95 %CI: 0.58-0.89; p = 0.003) and a comparable relative reduction on major adverse cardiovascular events. There was potential heterogeneity by subgroup (p = 0.06), with a stronger relative reduction for stroke in the five ASCVD trials (RR=0.48, 95 %CI:0.30-0.77; p = 0.003) than the non-cardioembolic ischemic stroke/TIA population (RR=0.80, 95 %CI:0.63-1.02; p = 0.07). Colchicine was associated with a small, non-significant increase in all-cause mortality (RR: 1.09; 95 %Cl: 0.85-1.40, p = 0.49) but not cardiovascular death (RR: 0.92; 95 %Cl: 0.65-1.29, p = 0.61).

Conclusion: Low-dose colchicine treatment decreases stroke and major adverse cardiovascular event risk in patients with ASCVD and potentially in patients following a non-cardioembolic ischemic stroke/TIA. Among every 1000 patients treated over 2 years, approximately 6.6 strokes and 24 major adverse cardiovascular events are avoided.