Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction (COLCOT)

The COLCOT (Colchicine Cardiovascular Outcomes Trial) randomized 4,745 patients within 30 days of a myocardial infarction to low-dose colchicine (0.5 mg/day) or placebo on top of standard therapy (including statins and antiplatelet agents), with a primary outcome of the composite of cardiovascular death, resuscitated cardiac arrest, MI, stroke, and urgent coronary revascularization.

Colchicine reduced the primary composite endpoint by 23% (HR 0.77, 95% CI 0.61–0.96) over a median follow-up of 22.6 months. The benefit was driven primarily by reductions in stroke (HR 0.26) and urgent revascularization (HR 0.50). Gastrointestinal adverse events were more common with colchicine; pneumonia occurred numerically more often in the colchicine group, though the difference was not statistically significant.

COLCOT, along with the LoDoCo2 trial (in stable CAD) and the CANTOS trial (canakinumab), established inflammation as a causal and modifiable risk factor for cardiovascular events beyond lipid levels. The novel aspect of colchicine’s mechanism — inhibition of microtubule polymerization, NLRP3 inflammasome suppression, and neutrophil activation — provides cardiovascular benefit through a pathway entirely separate from lipid lowering.

Colchicine 0.5 mg/day is now included in ACC/AHA and ESC guidelines as an option for secondary prevention in patients with established ASCVD, particularly those with residual inflammatory risk indicated by elevated hsCRP.

We rate the evidence strong. The COLCOT trial establishing that low-dose colchicine reduces major cardiovascular events by 23% after myocardial infarction — landmark evidence for anti-inflammatory therapy as a component of secondary cardiovascular prevention independent of lipid lowering.