Aernoud Fiolet

235 Short-term effect of low-dose colchicine on biomarkers INTRODUCTION I nflammation plays a pivotal role in the complex pathophysiology of atherothrombosis. 1,2 Part of the inflammatory response may be initiated by the crystallization of cholesterol in the lipid pool of the atheroma. Leukocyte chemotaxis and inflammatory response can compromise stability of thin capped fibroatheromata. In addition, the cholesterol crystals may pierce through the plaque cap causing direct disruption of the cap. 3 Important chemokines in these processes are interleukin (IL)– 1 and cytosolic multimeric protein complexes called inflammasomes. 4–6 Dampening the inflammatory response in atherosclerosis with anti-inflammatory drugs has yielded contradictory results. Anti-inflammatory treatment with canakinumab, a therapeuticmonoclonal antibodytargeting interleukin-1 β , resulted in a detectable anti-inflammatory biochemical response and was associated with beneficial effects on major clinical outcomes in cardiovascular disease. Treatment with low-dose methotrexate however, did not show biochemical or clinical response. 7,8 Colchicine is an anti-inflammatory drug highly effective in reducing crystal induced inflammation in gout 9 . It is currently investigated as a potential anti-inflammatory drug in several atherosclerotic vascular disease states. 10 Although there is some evidence on its clinical efficacy in cardiovascular disease, the effects on downstream markers of inflammation may vary, and have not yet been investigated in patients with chronic coronary artery disease. 11–14 Colchicine has a narrow therapeutic index. First, competition with Cytochrome P450 3A4 (CYP3A4) or P-glycoprotein metabolizing drugs may lead to decreased clearance of colchicine or alter pharmacodynamics of CYP3A4 substrates such as statins. Second, colchicine in high dose can modulate myeloid cell lines due to its anti-proliferative properties. 15,16 Third, colchicine is relatively contra-indicated in patients with advanced renal insufficiency, although possible reno-protective properties of the drug are increasingly investigated in patients with renal disease. 17 The aim of this study was to investigate whether 30 days exposure to colchicine 0.5mg once daily leads to a reduction in inflammatory biomarkers in patients with chronic coronary artery disease and to investigate effects of treatment on lipid fractions, blood indices, and renal function.