Aernoud Fiolet

384 Chapter 16 we review safety outcomes presented in available meta-analyses in a broad array of medical conditions. Secondly, we analyse the risks of drug toxicity and potential drug interactions. Based on the available evidence, we conclude that colchicine can be trialled in a safe manner in the majority of patients with coronary disease. The current available evidence justifies a properly designed and adequately powered clinical trial to evaluate the efficacy of colchicine in patients with chronic coronary disease. PART II: EFFICACY AND SAFETY OF COLCHICINE IN CORONARY DISEASE In Chapter4 ,weproposemethods to investigatetheefficacyof colchicine inpatients with chronic coronary disease by designing the Low-Dose Colchicine 2 (LoDoCo2) trial. Firstly, we provide an overview of the available data from experimental studies that suggest an atheroprotective effect of colchicine. Secondly, we propose to include “all-comers” from the outpatient clinic in the trial, rather than selecting participants with an inflammatory phenotype. Characteristics of the drug make patients with severe cardiorenal failure unsuitable as participants. In addition, we provide a predefined hierarchical method of statistical testing for the primary and secondary end points in order to reduce the risk of false-positive testing due to Type I statistical errors. Furthermore,we formulate end point definitions to be used by the blinded end point adjudication committee. Lastly, we provide the baseline data of the cohort, recruited in 2 countries. We conclude that these patients are an appropriate reflection of patients in daily clinical practice, and that this trial will contribute to the evaluation of the efficacy of anti-inflammatory treatment in coronary disease. In Chapter 5 , we present the main results of the LoDoCo2 trial. The trial was conducted between 2014 and 2019. We randomized 5,522 patients to receive colchicine 0.5mg once daily or placebo. After a median follow-up of 28.6 months (interquartile range 20.5–44.4 months) complete end point data were available for all but one patient (99.99%). The primary end point, a composite of cardiovascular death, spontaneous (nonprocedural) myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularisation occurred in 187 patients (6.8%) in the colchicine group and in 264 patients (9.6%) in the placebo group (incidence 2.5 versus 3.6 events per 100 person-years; hazard ratio, 0.69; 95% confidence interval, 0.57 to 0.83; P < 0.001). The secondary end point, a composite of cardiovascular death, spontaneous myocardial infarction, or ischemic stroke, occurred in 115