Aernoud Fiolet

122 Chapter 5 trial regimens were continued until the completion of the trial. Moreover, clinical follow-up was continued until the date of trial completion regardless of premature discontinuation of colchicine or placebo. End points The primary end point was a composite of cardiovascular death, spontaneous (nonprocedural) myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization. Secondary end points,whichwere tested in hierarchical fashion, were ranked in the following order: the composite of cardiovascular death, spontaneous myocardial infarction, or ischemic stroke (key secondary end point); the composite of spontaneous myocardial infarction or ischemia-driven coronary revascularization; the composite of cardiovascular death or spontaneous myocardial infarction; ischemia-driven coronary revascularization; spontaneous myocardial infarction; ischemic stroke; death from any cause; and cardiovascular death. The list of end points, including the primary end point, was revised several times during the trial; the latest and final revision took place in January 2020 before the datawere unblinded. End points were adjudicated by a committeewhose members were unaware of the trial-group assignments. Additional end points and definitions are provided in Table S2. Statistical analysis The trial was designed to accrue a minimum of 331 primary end-point events and to have a minimum follow-up of 1 year. On the basis of a target enrollment of 6053 patients in the open-label run-in phase, with 5447 undergoing randomization after screening, we estimated that the trial would have more than 90% power, at a two- sided alpha level of 0.05, to detect a 30% lower rate (i.e., a hazard ratio of 0.70) of a primary composite end-point event in the colchicine group than in the placebo group, assuming a 10% rate of discontinuation of colchicine or placebo and an annual rate of the primary end point in the control group of 2.6%. Details of the statistical methods are provided in the Supplementary Appendix. Themain analysiswas based on the time from randomization to the first occurrence of any component of the primary composite end point. If the incidence of the primary end point was significantly lower in the colchicine group than in the placebo group (P<0.05), then the ranked secondary end points were tested in a hierarchical fashion at a significance level of 0.05 in order to preserve the alpha level. The original protocol did not include a plan to adjust for multiple testing;