Aernoud Fiolet

386 Chapter 16 coronary syndrome and treatment effect. We conclude that this confirms a benefit of the drug for a broad spectrum of patients and can offer clinical guidance for the initiation of therapy. PART III: INSIGHTS IN MECHANISM AND TOLERANCE In Chapter 9 , we analyse the short-term biochemical effects of low-dose colchicine using a longitudinal study design. We show that the drug is associated with a 40% reduction in high-sensitivity C-reactive protein level and a 16% reduction in interleukin-6 level. Both leukocyte count and thrombocyte count decreased during follow-up. A 2% decrease in estimated glomerular filtration rate was observed. We discuss that the effects on the cell lines are expected and that the origin of the effect on renal clearance is unclear. We conclude that long-term and placebo-controlled analyses should help to evaluate whether these signals are true and if so, whether they are clinically relevant. In Chapter 10 , we conduct an advanced analysis to evaluate the short-term effect of colchicine on a broad array of proteins using a longitudinal study design. We conclude that short term colchicine exposure is associated with a marked anti-inflammatory effect, which involves nucleotide-binding oligomerisation domain–, leucine-rich repeat–, and pyrin domain–containing protein 3 (NLRP3) inflammasome, as well as proteins related to neutrophil activity. In Chapter 11 , we aim to confirm the hypothesis that low-dose colchicine reduces inflammasome activity using a placebo-controlled study design. We find lower levels of inflammatory biomarkers in patients after 1 year of treatment with colchicine as compared to those taking the placebo. In addition, we quantify the effect of the drug on extracellular vesicle NLRP3 inflammasome protein levels. We show that colchicine is associated with reduced NLRP3 inflammasome protein levels. We conclude that the drug reduces important inflammatory markers. These particular changes however are not the sole mechanism of action in atherosclerosis. In Chapter 12 , we return to the clinical perspective and investigate if there are demographical or medical parameters that are associated with early intolerance to low-dose colchicine in patients with coronary disease. We find that intolerance of colchicine is seen in approximately one of every 11 patients. It most often concerns gastrointestinal upset, myalgia, or fatigue. Female sex is the strongest