Colchicine for Secondary Cardiovascular Prevention in Coronary Disease

A large body of evidence has demonstrated the important role of inflammation in atherosclerosis.1 Inhibition of interleukin-1β by the injectable antibody canakinumab reduced the rate of cardiovascular events by 15% in the CANTOS study (Canakinumab Anti-inflammatory Thrombosis Outcomes Study).2 However, canakinumab is extremely expensive and not approved for cardiovascular prevention, and was associated with a slight but significant increase in septic shock and reduced risk of cancer mortality. In addition, methotrexate, another agent with anti-inflammatory properties, failed to provide beneficial effects on cardiovascular outcomes or biomarkers of inflammation in a large randomized trial.3 In contrast, colchicine is an orally administered, inexpensive anti-inflammatory medication that has been shown to reduce significantly nonfatal cardiovascular events in patients with coronary artery disease.4–6 The COLCOT trial (Colchicine Cardiovascular Outcomes Trial) randomly assigned 4745 patients to receive colchicine 0.5 mg once daily or placebo within 30 days after a myocardial infarction (MI).4 The median duration of follow-up was 22.6 months. Low-dose colchicine reduced the risk of the primary end point of time to first cardiovascular event, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina requiring coronary revascularization by 23% compared to placebo. The risk of the total burden of these primary ischemic cardiovascular events (both first and recurrent) was also reduced by 34% with colchicine in COLCOT. The benefit was due to effects on all components of the primary end point, with hazard ratios of 0.26 (95% confidence interval [CI], 0.10–0.70) for stroke; 0.50 (95% CI, 0.31–0.81) for urgent hospitalization for angina requiring coronary revascularization (the main weight); 0.84 (95% CI, 0.46–1.52) for cardiovascular death; and 0.91 (95% CI, 0.68–1.21) for MI. Colchicine was also shown to have a more marked effect on MI when initiated within the first 3 days after the acute coronary syndrome.5 The results of the LoDoCo2 trial (Low-Dose Colchicine-2) complemented those of COLCOT. LoDoCo2 included 5522 patients with chronic coronary disease who were randomized to receive low-dose colchicine or placebo.6 Patients were followed for a median duration of 28.6 months. The risk of the primary end point of cardiovascular death, MI, ischemic stroke, or ischemia-driven coronary revascularization was reduced by 31% by colchicine. As compared with placebo, colchicine reduced the risk of cardiovascular death, MI and stroke by 28% and that of MI by 30%. It is against the backdrop of these trials that the results of the smaller Australian COPS study (Colchicine in Patients With Acute Coronary Syndrome) are reported by Tong et al in this issue of Circulation.7 COPS was a study of 795 patients with an © 2020 American Heart Association, Inc.