Colchicine in coronary artery and cerebrovascular disease: “Old skin for the new ceremony”

Table 1 Key studies about colchicine in acute coronary syndromes, chronic coronary syndromes and cerebrovascular disease

Study	Year	Study design	Comparison	Colchicine dose and duration	Primary endpoint	Sample size	Results
LoDoCo[72]	2013	Prospective, randomized, observer-blinded endpoint	Low-dose colchicine vs no colchicine	0.5 mg/day; median 3 years follow-up	Composite incidence of acute coronary syndrome, out-of-hospital cardiac arrest, or noncardioembolic ischemic stroke	532 patients	Primary endpoint: 5.3% (colchicine) vs 16.0% (no colchicine). Hazard ratio (HR) 0.33; 95%CI: 0.18 to 0.59; (P < 0.001). Significantly lower risk with colchicine
COLCOT[8]	2019	Randomized, double-blind, placebo-controlled, investigator initiated, event-driven trial	Low-dose colchicine vs Placebo	0.5 mg once daily; median 22.6 months follow-up	Composite of death from cardiovascular causes, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalization for angina leading to coronary revascularization	4745 patients	Primary endpoint: 5.5% (colchicine) vs 7.1% (placebo). HR: 0.77; 95%CI: 0.61 to 0.96, (P = 0.02). Significantly lower risk with colchicine
COPS[71]	2020	Randomized, double-blind, placebo-controlled trial	Low-dose colchicine vs placebo	0.5 mg twice daily for the first month, then 0.5 mg daily for 11 months; 12 months follow-up	Composite of all-cause mortality, ACS, ischemia-driven (unplanned) urgent revascularization and noncardioembolic ischemic stroke	795 patients	Primary endpoint: 24 events (colchicine) vs 38 events (placebo). HR: 0.65; 95%CI: 0.38 to 1.09; (P = 0.10). The addition of colchicine to standard medical therapy did not significantly affect cardiovascular outcomes at 12 months in patients with ACS
LoDoCo2[9]	2020	Randomized, controlled, double-blind, investigator initiated, event-driven trial	Low-dose colchicine vs placebo	0.5 mg once daily (after 1-month run-in phase); median 28.6 months follow-up	Composite of cardiovascular death, spontaneous (nonprocedural) myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization	5522 patients	Primary endpoint: 6.8% (colchicine) vs 9.6% (placebo). HR: 0.69; 95%CI: 0.57 to 0.83; (P < 0.001). Significant risk reduction with colchicine
COVERT-MI[67]	2021	Investigator-initiated, randomized, double-blinded placebo-controlled, multicenter trial	Low-dose colchicine vs placebo	2 mg loading dose followed by 0.5 mg twice a day for 5 days. Duration was from admission to day 5	Infarct size in grams of left ventricular mass assessed by late gadolinium enhancement CMR at 5 days	192 patients	At 5 days, gadolinium enhancement did not differ between colchicine and placebo groups (P = 0.87)
CONVINCE[13]	2024	Randomized, parallel-group, open-label, blinded endpoint assessed trial	Low-dose colchicine plus guideline-based usual care vs guideline-based usual care only	0.5 mg orally per day; median 33.6 months follow-up	Composite of first recurrent non-fatal ischemic stroke, myocardial infarction, cardiac arrest, or hospitalization for unstable angina or vascular death	3154 patients	Primary endpoint: 9.8% (colchicine plus usual care) vs 11.7% (usual care only). HR: 0.84; 95%CI: 0.68 to 1.05; (P = 0.12). The difference was not statistically significant in the intention-to-treat analysis
CHANCE-3[14]	2024	Multicenter, double blind, randomized, placebo controlled trial	Low-dose colchicine vs Placebo	0.5 mg twice daily (days 1-3), then 0.5 mg daily (days 4-90). Duration was from admission to day 90	Any new stroke (ischemic or hemorrhagic) within 90 days after randomization	8343 patients	Primary endpoint (stroke): 6.3% (colchicine) vs 6.5% (placebo). HR: 0.98; 95%CI: 0.83 to 1.16; (P = 0.79). The trial did not provide sufficient evidence that low-dose colchicine could reduce the risk of subsequent stroke within 90 days
CLEAR[15]	2024	Multicenter trial with a 2-by-2 factorial design, randomized, placebo-controlled trial	Colchicine plus placebo vs colchicine plus spironolactone vs spironolactone plus placebo vs placebo only	Initially 0.5 mg twice daily (≥ 70 kg) or once daily (< 70 kg) for 90 days, then once daily for all. Modified to 0.5 mg once daily throughout from September 2020. Median 3 years follow-up	Composite of death from cardiovascular causes, recurrent myocardial infarction, stroke, or unplanned ischemia-driven coronary revascularization	7062	Primary endpoint: 9.1% (colchicine) vs 9.3% (placebo). HR: 0.99; 95%CI: 0.85 to 1.16; (P = 0.93). Treatment with colchicine, when started soon after myocardial infarction and continued for a median of 3 years, did not reduce the incidence of the composite primary outcome

ACS: Acute coronary syndromes; CCS: Chronic coronary syndromes; CMR: Cardiac magnetic resonance.