Aernoud Fiolet

238 Chapter 9 For exploratory purposes, interaction of the estimated treatment effect in selected subgroups was tested using a mixed effects model with random intercepts and slopes with log transformation of outcome data. All subgroups were included in the final model to adjust for confounding. All calculations were done with R (The R Foundation for Statistical Computing, version 3.6.0. using the packages “LMER” and “boot”). Ethical approval and funding The study was approved by a central ethics committee (MEC-U, Nieuwegein, the Netherlands). All patients signed informed consent prior to participation. This work was supported by a governmental grant from The Netherlands Organisation for Health Research and Development [grant number 848015014]. The drug was supplied free of charge by TioPharma (Oud-Beijerland, the Netherlands). The funders and drug supplier had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors confirm that all ongoing and related trials for this drug/interventionare registeredand themain trial is registered in the Australian Clinical Trials Registry (ACTRN12614000093684). There are no conflicts of interests by the authors. RESULTS Blood samples were available in 337 patients. Major reasons for exclusion where hs-CRP <2 mg/L (n = 184) or intolerance to the drug (n = 7), mainly in the form of gastro-intestinal upset (Fig 1). 138 patients were included in the final analysis. Median age was 65 years and 82% were male (Table 1). Of these, 115 (83%) had a previous acute coronary syndrome with the last event occurring a median of 23 months prior to inclusion (interquartile range [IQR] 9–76 months). Active smokers comprised 14% of the cohort and 20% had diabetes. All had single or dual antiplatelet therapy or anticoagulants, 88%were treated with statins and 59%with high dose statins.