Aernoud Fiolet

178 Chapter 7 The presence of heterogeneity of treatment effect among studies was assessed by calculating a Higgins and Thompsons’ I 2 index, in which heterogeneity was considered to be low if the I 2 index was around 25%, moderate if around 50%, and high if around 75%. 19,20 Publication bias was not assessed due to the small number of included studies. The methodological quality of the randomized trials was assessed by the Cochrane Collaboration’s revised Risk-of-Bias 2 tool. 21,22 Two investigators (T.S.J.O. and A.T.L.F.) independentlyassessed the five domains for risk of bias: the randomization process, deviations from intended interventions, missing outcome data, measurement of the outcome, and selection of the reported results. All statistical analyses were performed using R (The R Foundation for Statistical Computing, version 3.6.0) using the metaphor package (version 2.4-0). Illustrations were made with BioRender.com. The corresponding author had full access to all the data and had final responsibility for the decision to submit for publication. The data underlying this article will be shared on reasonable request to the corresponding author. RESULTS From 536 initial citations identified by the search, we included five randomized trials that met the inclusion criteria (Supplementary material, Figure SA1). 13,14,23–25 These five trials involved 11 816 patients randomly allocated to colchicine (n=5918) or placebo or standard treatment (n=5898). The key study features of the five trials are reported in Table 1 and Supplementary material, Table SA1. The trial by Deftereos et al., the COLCOT trial, the COPS trial and the LoDoCo2 trial were all randomized, placebo-controlled, double-blind, clinical trials. 13,14,23,25 The LoDoCo was a single-centre, open-label trial of colchicine vs. control on a background of optimal medical treatment in patients with chronic coronary disease, with blinded endpoint adjudication (a PROBE design). 24 The trial by Deftereos et al. 23 was single-centre and enrolled stable patients with diabetes who underwent percutaneous coronary intervention with bare-metal stent insertion. COLCOT and COPS enrolled patients with recent myocardial infarction (<30days) or acute coronary syndrome, respectively. 13,25 The LoDoCo2 was a multi-centre international trial enrolling patients with chronic coronary disease that used an open-label run-in period of 30days. 14 All trials used a dose regimen of colchicine 0.5mg once daily except the trial by Deftereos et al., 23 which used a dose regimen