Clinical Question

Does colchicine reduce the risk of cardiovascular events in patients with chronic coronary artery disease?

Bottom Line

Colchicine, 0.5 mg daily, significantly reduces the risk of myocardial infarction (MI) and ischemia-driven revascularization. For the compositive outcome of cardiovascular death, MI, or ischemic stroke, the number needed to treat (NNT) was 67 over 29 months. The cost is $8 per month in Canada and $65 per month in the United States. There was increased noncardiovascular mortality, but no clear pattern with regard to cause of death. (Level of Evidence = 1b)

Synopsis

Colchicine has been shown to reduce a broad composite of cardiovascular outcomes in patients with recent MI, and a small open-label trial of patients with chronic coronary artery disease showed a similar outcome. The authors identified 6,528 patients, 35 to 82 years of age, with documented coronary artery disease on computed tomography angiogram, by invasive angiography, or with a coronary artery calcium score of at least 400 Agatston units. Patients with at least moderate renal disease, severe valvular heart disease, or heart failure were excluded, as were those who were intolerant of colchicine. The study began with an open-label run-in period that excluded 15% of patients, largely because of drug adverse effects. The remaining 5,522 were randomized to receive colchicine, 0.5 mg once daily, or placebo. Analysis was by intention to treat, and groups were similar at baseline. The patients' mean age was 66 years, 15% were women, 12% were smokers, and 18% had diabetes. Most had a previous revascularization, largely stenting. All patients were from the Netherlands (66%) or Australia (34%). Patients were followed up for a median of 29 months, and 10.5% in each group stopped taking the medication or placebo. There were no differences between groups in withdrawals or perceived adverse effects. The authors examined four different composite outcomes. They found a reduction in the primary composite of cardiovascular death, MI, ischemic stroke, or coronary revascularization due to ischemia with colchicine (6.8% vs. 9.6%; P < .001; NNT = 36 for 29 months). The composite that dropped revascularization showed a somewhat smaller difference between groups, but a statistically and clinically significant result (4.2% vs. 5.7%; P = .007; NNT = 67 for 29 months). Regarding individual endpoints, MI and ischemia-driven coronary revascularization were significantly reduced with colchicine, with no significant difference in ischemic stroke, cardiovascular mortality, or all-cause mortality. There were trends toward fewer cardiovascular deaths, but more noncardiovascular deaths (1.9% vs. 1.3%; hazard ratio = 1.51; 95% CI, 0.99 to 2.31). Myalgias were slightly more common in the colchicine group (21.2% vs. 18.5%; P < .05; number needed to harm = 37 over 29 months).

Study design: Randomized controlled trial (double-blinded)

Funding source: Government

Allocation: Concealed

Setting: Outpatient (any)

Reference: Nidorf SM, Fiolet ATL, Mosterd A, et al. LoDoCo2 Trial InvestigatorsColchicine in patients with chronic coronary disease. N Engl J Med. 2020;383(19):1838–1847.

Editor's Note: Dr. Ebell is deputy editor for evidence-based medicine for AFP and cofounder and editor-in-chief of Essential Evidence Plus, published by Wiley-Blackwell.