Aernoud Fiolet

250 Chapter 9 eGFR is different from the anti-inflammatory effects of colchicine and may be due to a direct hemodynamic effect on the glomerulus. 37,38 Another effect could be the Hawthorne effect, i.e. an indirect effect of trial participation. Whether the patients increased their compliance with drugs affecting glomerular hemodynamics such as angiotensin converting enzyme inhibitors was not be assessed in the current study setup, but is a known effect in trial participants. 39,40 Limitations A methodological limitation of our study is the paired testing with the absence of a parallel control group. This is inherent to the design of the study as it was part of the run-in phase prior to randomization of three sites in a clinical trial. Due to the selection of hs-CRP ≥2 mg/L, part of the change in hs-CRP may be explained by regression to the mean or natural course. However, changes in hs-CRP are more pronounced than those observed in the placebo arm of the similar CANTOS population (change of -40% in this cohort versus -17% in CANTOS), suggesting the CRP decrease is perhaps only partially influenced by preselection and natural course. In addition, no change in IL-6 was seen in the placebo arm of CANTOS. 7 Finally, the subgroup analyses have an exploratory purpose only. Since the study was not designed to assess differences between subgroups, the limited sample size increases risk for type 2 errors in these observations. Conclusion One-month exposure to low-dose colchicine was associated with a reduction of the inflammatory markers hs-CRP and IL-6 in patients with chronic coronary artery disease and baseline hs-CRP ≥2 mg/L. An effect was seen on estimated glomerular filtration rate, leukocyte and thrombocyte cell count, which warrants placebo-controlled and longer follow-up of these parameters. Whether the anti- inflammatory and other effects observed in this study are solely contributable to colchicine should be confirmed in placebo-controlled assessment. Whether this effect translates into a clinical benefit has to be awaited. Observations thus far support ongoing clinical research in colchicine as anti-inflammatory drug in atherosclerosis.