Aernoud Fiolet

293 Predictors of early intolerance to low-dose colchicine in patients with coronary disease INTRODUCTION C olchicine is a well-known anti-inflammatory drug used in the treatment of gouty arthritis, Familial Mediterranean Fever and pericarditis. The mechanisms of action of colchicine are broad and involve inhibition of microtubule formation, inhibition of leukocyte chemotaxis and adhesion, modulation of monocyte response and direct inhibition of various pro-inflammatory cytokines such as interleukin-6, interleukin-1 β and C-reactive protein. 1–3 Its efficacy in gouty arthritis seems to be related to its ability to reduce crystal induced inflammation following urate crystallization. 4 Observational safety data suggest early intolerance may occur in certain patients. Common adverse effects are gastro-intestinal upset and myalgia and occur early after treatment initiation in 10-15% of patients. 5,6 The drug has a narrow therapeutic range and can be toxic in high doses, when renal or hepatic elimination is impaired or as a consequence of drug-drug interaction. 7,8 Recently, several randomized clinical trials demonstrated efficacy of low-dose colchicine in preventing major adverse cardiovascular events in patients with acute and chronic coronary disease. 9,10 Patients with coronary disease are often treated with a number of concomitant drugs and may have various cardiovascular comorbidities. Details on the occurrence of early intolerance of low-dose colchicine in these patients are not yet described. With the current study, we aimed to assess the occurrence of early intolerance to low-dose colchicine, describe the nature of the perceived side effects and investigate which patient characteristics and concomitant drugs are associated with early intolerance. METHODS Study design and population This study was a prospective, open-label study of colchicine 0.5mg once daily in patients with coronary disease, designed as substudy of the Dutch cohort of the second Low-dose colchicine (LoDoCo2) trial. Design and primary results of the trial have been published before. 10,11 Recruitment of patients took place in out- patient cardiology practices from 30 Dutch non-academic hospitals.