Role of anti-inflammatory agent colchicine in atherosclerotic cardiovascular disease

Table 1 Summary of Colchicine trial outcomes in atherosclerotic cardiovascular disease

Trial number	Trial name/year	Official title	Details	Outcome	Notes
ACTRN 12610000293066	LoDoCo/2013	Low-Dose Colchicine for Secondary Prevention of Cardiovascular Disease	n = 532; Patients diagnosed with stable, angiographically confirmed CAD who have maintained clinical stability for a minimum of six months were randomly assigned to receive either standard treatment in conjunction with 0.5 mg of daily colchicine or standard treatment alone	Colchicine had a lower composite outcome of OHCA, ACS, or non-cardioembolic ischemic stroke vs control (5.3% vs 16%; HR, 0.33; 95%CI: 0.18-0.59; P < 0.001)	The most common side effect was GI disturbance
NCT02551094	COLCOT/2019	Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction	n = 4745; Patients within 30 days post MI were randomized to either standard therapy plus placebo or standard therapy plus 0.5 mg daily colchicine	Lower incidence of MACE in the colchicine group (5.5% vs 7.1%; HR, 0.77; 95%CI: 0.61-0.96; P = 0.02)	The most common side effect was GI disturbance
ACTRN12615000861550	COPS/2020	Colchicine in Patients with Acute Coronary Syndrome: The Australian COPS Randomized Clinical Trial	n = 795; Patients presenting with ACS with evidence of CAD (angiographically managed with PCI or medical therapy) were randomized to receive either standard therapy plus colchicine (0.5 mg BID for the first month post ACS, then 0.5 mg daily for 11 months) or placebo plus standard therapy	There was no statistically significant difference between the two groups (HR, 0.65; 95%CI: 0.38-1.09; P = 0.1) in the primary outcome (i.e., a composite of all-cause mortality, ACS [STEMI/NSTEMI/UA], ischemia-driven urgent revascularization, and noncardioembolic ischemic stroke). However, the colchicine arm showed lower incidence of the primary outcome when all-cause mortality was replaced with CV mortality (5% vs 9.5%; HR, 0.51; 95%CI: 0.29-0.89; P = 0.019)	The most common side effect was GI disturbance
ACTRN12614000093684	LoDoCo2/2020	Colchicine in Patients with Chronic Coronary Disease	n = 5552; Patients with stable CAD (angiographically or CAC score ≥ 400 AU) who were clinically stable for ≥ 6 months were randomized to either standard therapy plus 0.5 mg daily colchicine or to standard therapy plus placebo. A total of 3,179 patients had ACS for a duration of 24 months or more prior to randomization	Colchicine demonstrated a reduced occurrence of cardiovascular death, spontaneous myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization compared to placebo (6.8% vs 9.6%; HR, 0.69; 95%CI: 0.57-0.83; P < 0.001)	The colchicine group experienced a higher occurrence of non-cardiovascular deaths, although this was not statistically significant (incidence, 0.7 compared to 0.5 events per 100 person-years; HR, 1.51; 95%CI: 0.99-2.31)
NCT03048825	CLEAR SYNERGY/2024	Colchicine in Acute Myocardial Infarction	n = 7062; Patients within 72 hours post MI were randomized to either standard therapy plus 0.5 mg daily colchicine or to standard therapy plus placebo	There was no significant difference in MACE outcomes observed between the two groups (9.1% compared to 9.3%; HR, 0.99; 95%CI: 0.85-1.16; P = 0.93). Additionally, there was no notable difference in all-cause mortality (4.6% compared to 5.1%; HR, 0.90; 95%CI: 0.73-1.12)	A higher incidence of diarrhea was reported in the colchicine group (6.6% vs 10.2%; P < 0.001)

LoDoCo: Low-Dose Colchicine; CAD: Coronary artery disease; OHCA: Out-of-hospital cardiac arrest; ACS: Acute coronary syndrome; HR: Hazard ratio; CI: Confidence interval; GI: Gastrointestinal tract; COLCOT: Colchicine Cardiovascular Outcomes Trial; MI: Myocardial infarction; MACE: Major adverse cardiac event; COPS: Colchicine to Improve Cardiovascular Outcomes in ACS Patients; PCI: Percutaneous coronary intervention; BID: Twice daily; STEMI: ST-segment elevation myocardial infarction; NSTEMI: Non-ST-segment elevation myocardial infarction; UA: Unstable angina; CV: Cardiovascular; LoDoCo2: Low Dose Colchicine for Secondary Prevention of Cardiovascular Disease 2; CAC: Coronary artery calcium; AU: Agatston unit; CLEAR SYNERGY: Colchicine in Acute Myocardial Infarction.