Clinical Pearls & Morning Reports
Despite lifestyle changes and risk-factor reduction, patients with chronic coronary disease remain at high risk for acute cardiovascular events. The central role of inflammation in the progression of coronary disease is well recognized. Nidorf et al. conducted a randomized, controlled, double-blind trial of low-dose colchicine to determine whether 0.5 mg of colchicine once daily, as compared with placebo, prevented cardiovascular events in patients with chronic coronary disease. Read the NEJM Original Article here.
Q: Describe a way in which colchicine differs from canakinumab.
A: Colchicine is an antiinflammatory drug originally extracted from the autumn crocus (Colchicum autumnale) and was used by the ancient Greeks and Egyptians. In contrast to selective inhibition of interleukin-1β by canakinumab, colchicine has broad cellular effects that include inhibition of tubulin polymerization and alteration of leukocyte responsiveness.
Q: What were the findings of the CANTOS and COLCOT trials?
A: The possibility that antiinflammatory therapy may improve cardiovascular outcomes was first highlighted in the Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS) involving patients with a history of myocardial infarction and an elevated baseline level of C-reactive protein; the results showed that the risk of recurrent cardiovascular events was lower among those who received canakinumab than among those who received placebo. In the Colchicine Cardiovascular Outcomes Trial (COLCOT) involving patients who had a myocardial infarction within 30 days before enrollment, the percentage of those who had the composite end point of cardiovascular death, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalization for angina leading to coronary revascularization was lower among those who received 0.5 mg of colchicine once daily than among those who received placebo.
A: Among patients with chronic coronary disease, most of whom were already receiving proven secondary prevention therapies, 0.5 mg of colchicine once daily resulted in a 31% lower relative risk of cardiovascular death, spontaneous myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization (the primary end point) than placebo, with a hazard ratio of 0.69. The effects of colchicine appeared to be consistent across each component of the primary end point and all secondary composite end points. Among the patients who were enrolled in the run-in phase, 15.4% did not undergo randomization; the most common reason was gastrointestinal upset.
A: The incidence rates of death from any cause and noncardiovascular death were higher with colchicine than with placebo. The observed between-group difference in the incidence of noncardiovascular death was not significant, as shown by the 95% confidence interval, and could have been due to chance, although the hazard ratio of 1.51 is of potential concern. The individual causes of death do not permit a clear interpretation of this finding. In the COLCOT trial, noncardiovascular death occurred in 23 patients who received colchicine and in 20 patients who received placebo.