Aernoud Fiolet

248 Chapter 9 DISCUSSION This study showed that patients with chronic coronary artery disease and a pro- inflammatory state defined by hs-CRP ≥ 2 mg/L, had a significant decrease in both hs-CRP and IL-6 after one month of colchicine exposure. No clinically relevant changes in lipid spectrum were observed. A small decrease in mean corpuscular volume was observed, as well as a decrease in leukocyte and thrombocyte number and a small decrease in estimated glomerular filtration rate. The present study extends our knowledge of the anti-inflammatory effect of 0.5mg colchicine once daily to patients with chronic coronary artery disease. Anti-inflammatory effects The direction and extent of the change in inflammatory markers after exposure to colchicine in this pro-inflammatory population with coronary artery disease compares to observations from previous studies in heart failure and patients with metabolic syndrome. Although absolute reduction of hs-CRP and IL-6 were larger in these studies in which baseline levels were higher, the relative reduction was similar. The reduction in the current study was achieved with a lower dose of colchicine. 21,22 Systemic hs-CRP and IL-6 reduction have not been observed when administrating colchicine directly after acute myocardial infarction. 14,23,24 This may represent limitations in the anti-inflammatory effect of the drug in highly inflammatory conditions such a reperfusion injury and extended necrosis following acute myocardial infarction. 25,26 The magnitude of hs-CRP and IL-6 reduction found in the current study is similar to the effect of canakinumab used in the Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS). 7 Although hs-CRP <2 mg/L is associated with a lower risk for future cardiovascular events, hs-CRP itself carries no causal relationship to such incidents. 18 Inference to the magnitude of any clinical effect based on the current observations is thus explorative. Other surrogate markers for clinical outcomes are suggested to have a directly proportional relationship with hs-CRP concentration. For example, a change in hs-CRP has been shown to be associated in a linear manner with low attenuation plaque volume, a radiologic marker of plaque stability. 27 In contrast to hs-CRP, the evidence for a causal relation to levels of IL-6 and in particular IL– 1 beta and atherothrombosis has become more rigid after observational Mendelian randomization studies and results of the CANTOS