Colchicine in Patients with Chronic Coronary Disease

Colchicine in Patients with Chronic Coronary Disease
Radhika Patel, PharmD., Minnesota Community Care

Background: Inflammation plays a key role in the progression of coronary disease, particularly in individuals who are at high risk for acute cardiovascular events. In the 2019 Colchicine Cardiovascular Outcomes Trial (COLCOT), patients who had a myocardial infarction (MI) within 30 days before enrollment and received 0.5 mg of colchicine daily were less likely to have the composite end point of cardiovascular death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina leading to coronary revascularization than those who received placebo. However, it is unknown if colchicine has potential cardiovascular benefits in chronic coronary disease, not just in individuals who have had a past medical history of an MI.

Objective: To determine if colchicine can lower the risk of cardiovascular events in chronic coronary disease.

Study Design: Investigators performed a randomized, controlled, double-blind, intention-to-treat trial. The primary endpoints included a composite of cardiovascular death, spontaneous MI, ischemic stroke, or ischemia-driven coronary revascularization. The key secondary endpoint was similar to the primary outcome, but did not include the ischemia-driven coronary revascularization. Inclusion criteria included adults between the ages of 35-82 years with established coronary artery disease who had been clinically stable for at least 6 months. Exclusion criteria included moderate to severe renal impairment, severe heart failure, severe valvular heart disease, and known side effects from colchicine. The eligible subjects entered an open-label, run-in phase for one month in which they received 0.5 mg of colchicine daily. The patients who were stable without adverse effects, adhered to the open-label colchicine regimen, and remained willing to continue participation were randomly assigned in a 1:1 ratio to receive 0.5 mg of colchicine daily or matching placebo. 5,522 individuals underwent randomization in the study, 2,762 of whom were assigned to the colchicine arm and 2,760 to the placebo arm. The median duration of follow-up was 28.6 months.

Results: A primary end-point event occurred in 187 patients (6.8%) in the colchicine group and in 264 patients (9.6%) in the placebo group (incidence, 2.5 vs. 3.6 events per 100 person-years; HR 0.69 [95% CI 0.57-0.83, P<0.001). The key secondary end-point event occurred in 115 patients (4.2%) in the colchicine group and in 157 patients (5.7%) in the placebo group (incidence, 1.5 vs. 2.1 events per 100 person-years; HR 0.72 [95% CI 0.57-0.92], P = 0.007). In addition to colchicine, most patients were taking appropriate secondary prevention therapies for chronic coronary disease. In these patients, colchicine led to a 31% lower relative risk of cardiovascular death, spontaneous MI, ischemic stroke, or ischemia-driven coronary revascularization compared to placebo.

However, colchicine did not result in a lower incidence of death from any cause (73 vs. 60 fatalities; incidence, 0.9 vs. 0.8 events, respectively, per 100 person-years; 1.21 [95% CI 0.86-1.71]). The incidence of death from non-cardiovascular causes was higher in the colchicine group than in the placebo group (incidence, 0.7 vs. 0.5 events per 100 person-years; 1.51 [95% CI 0.99-2.31]). The risk of non-cardiovascular death, hospitalization for a GI cause, and myalgia were higher with colchicine, but were not statistically significant.

Conclusions: The primary and key secondary end-points had a lower incidence rate in the colchicine arm compared to placebo. Colchicine 0.5 mg daily resulted in a 31 percent lower relative risk of cardiovascular death, spontaneous MI, ischemic stroke, or ischemia-driven coronary revascularization. In addition, the incidence rates of various other secondary singular and composite endpoints (spontaneous MI or ischemia-driven coronary revascularization, cardiovascular death or spontaneous MI, ischemia-driven coronary revascularization, and spontaneous myocardial infarction) were all significantly lower with colchicine than with placebo. Based on this study, the effects of colchicine seem to be consistent across each component of the primary end point and many secondary endpoints. However, the study did also show a non-significant trend in higher rates of non-cardiovascular death among patients receiving colchicine.

Key Point: The results of the trial demonstrate that in patients with chronic coronary disease, the majority of whom were already taking appropriate secondary prevention therapies, there is a significantly lower occurrence of cardiovascular events while receiving colchicine 0.5 mg daily compared with placebo.

References:

  1. Nidorf SM, Mosterd FA, Eikelboom JW et. al. Colchicine in Patients with Chronic Coronary Disease. N Engl J Med. 2020.