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 I2 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 (pinteraction = 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.