Aernoud Fiolet

132 Chapter 5 effect of colchicine, as compared with placebo, on the primary end point was directionally consistent but appeared to be quantitatively larger in Australia than in the Netherlands (Fig. S2). DISCUSSION Amongpatientswithchroniccoronarydisease,most ofwhomwerealreadyreceiving proven secondaryprevention therapies, 0.5mg 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. 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 (Table S7) 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. 11 Among the patients who were enrolled in the run-in phase, 15.4% did not undergo randomization; the most common reason was gastrointestinal upset. Among the patients who had successfully completed the run-in phase and had undergone randomization, 10.5% in each trial group permanently discontinued colchicine or placebo prematurely. Our results provide no evidence for a clinically important interaction between low-dose colchicine and high-dose statins, which were used by 3413 patients (61.8%) in the trial. Myalgia, which was assessed only in the Netherlands cohort, was common in both trial groups, although it was reported more frequently in the colchicine group. The CANTOS trial provided evidence suggesting that inflammation plays a causal role in the pathogenesis of cardiovascular disease and related complications and that interventions to mitigate inflammation may reduce the risk of cardiovascular events. 6 Our results with colchicine are consistent with those obtained in the first LoDoCo trial and the COLCOT trial and provide further support for the potential benefits of antiinflammatory therapy in patients with coronary disease. 11,12 The