Aernoud Fiolet

187 The efficacy and safety of low-dose colchicine in patients with coronary disease Addressing safety on the level of serious but rarely occurring adverse events such as serious myotoxicity or neutropenia is limited by the low occurrence of such events necessitating longer follow-up and larger cohorts than are currently available. Other meta-analyses focusing on the safety of long-term colchicine for varied indications confirmed diarrhoea as a side effect of colchicine but did not identify increased frequency of other serious adverse events. 31,32 By reducing myocardial infarction and stroke, colchicine might be expected to affect related mortality. Although the incidence of cardiovascular deaths was lower in patients treated with colchicine, it was not significantly reduced. The trials all included patients with established cardiovascular disease, but the majority of fatalities were of non-cardiovascular origin. The increased incidence in non- cardiovascular death for colchicine cannot be explained by increased numbers of infections or cancer, has not been related to other causes, and was not observed in prior observational studies. The wide CIs reflect the limited power for these observations. To evaluate whether this finding represents a true signal, extended follow-up of patients enrolled in prior colchicine studies is required, and future trials should collect granular information on the origin of fatalities. 33,34 Although interpretation of fatality data is currently limited by low event numbers and statistical uncertainty, future data will contribute in more precise assessment of the net clinical benefit of colchicine in coronary disease. We acknowledge several limitations of our study. We used aggregated study-level data rather than individual participant data,However,while this limits our ability to examine subgroups of interest, this will not materially alter the overall conclusions drawn. The trials included patients with recent myocardial infarction as well as patients with chronic coronary disease. The inclusion criteria and definitions of endpoints varied among the included trials, but this did not lead to heterogeneity of the results. Furthermore, all trials included mostly older male patients without heart failure or renal failure. This limitation will need to be addressed in future and ongoing studies. Finally, data about ethnicity were lacking in all trials except COLCOT, potentially limiting generalizability of the results. In conclusion, the best available evidence indicates that low-dose colchicine reduced composite and individual cardiovascular outcomes in patients with coronary disease, when added to contemporary treatment with antiplatelet agents and lipid-lowering therapy.