Aernoud Fiolet

385 General summary 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; hazard ratio, 0.72; 95% confidence interval, 0.57 to 0.92; P = 0.007). There were no differences in the rate of premature discontinuation of trial medication between study arms and the occurrence of infections, cancer, and hospitalisation for gastrointestinal reasons were similar between groups. We conclude that in a randomized trial involving patients with chronic coronary disease, the risk of cardiovascular events was significantly lower among those who received 0.5 mg of colchicine once daily than among those who received placebo. In Chapter 6 , we provide some of the international responses to the results of the LoDoCo2 trial. We discuss the underrepresentation of female participants and postulate the sex-related difference in risk perception of trial participation of patients as one possible explanation. Secondly, we describe our caution in the interpretation of inherently underpowered subgroup analyses and the risks of chance findings due to multiplicity. Lastly, we mention the need to further analyse therapy response and investigate the mechanistic insights of this clinical effect. In Chapter 7 , we aim to present the most accurate estimate of the efficacy of colchicine in coronary disease by analysing all current clinical evidence in a tabular meta-analysis. In a pooled analysis, we demonstrate that low-dose colchicine comes with a 25% relative risk reduction for the composite of major cardiovascular events in patients with coronary disease. The effect is directionally consistent in acute and chronic coronary syndromes and occurs in both sexes. The effect is driven by a reduction in myocardial infarction (a 22% relative risk reduction), stroke (a 46% relative risk reduction), and coronary revascularisation (a 23% relative risk reduction). A decrease in cardiovascular death is counterbalanced by an increase in non-cardiovascular death. In Chapter8 ,we provide an in-depth analysis of the effects of colchicine in patients with a history of a recently diagnosed acute coronary syndrome (6 to 24 months prior to randomisation), a remote acute coronary syndrome (24 months to 7 years prior to randomisation), a very remote acute coronary syndrome (more than7 years prior to randomization), or no history of an acute coronary syndrome. We show that even patients with a very remote acute coronary syndrome have a high risk of a recurrent cardiovascular event, after correcting for possible confounding factors. Secondly, we do not find an interaction between the occurrence of a prior acute