Aernoud Fiolet

292 Chapter 12 ABSTRACT Background. Low-dose colchicine prevents major adverse cardiovascular events in patients with coronary disease. Some patients do not tolerate colchicine due to a variety of reasons. The occurrence of intolerance and association with clinical characteristics in patients with coronary disease are not yet described. Objectives. This study aimed to identifywhich clinical determinants are associated with intolerance to low-dose colchicine. Methods. This was a prospective, open-label study in which 4,048 patients with coronary disease were exposed to colchicine 0.5mg once daily. Intolerance due to any perceived side effects, gastrointestinal upset and myalgia were assessed after 30 days. Analyses were done using a multivariable logistic regression model. Results. 322 (8.9%) patients reported to be intolerant to the drug, due to gastro- intestinal upset (198, 53.9%), myalgia (61, 17.2%), fatigue (31, 8.8%) and non- specific symptoms (22, 6.2%). In a multivariable model, increased odds for intolerance due to any perceived side effects were seen with female sex (odds ratio, 1.61; 95% confidence interval 1.21 to 2.11, p < 0.01). Decreased odds were seen for obesity (odds ratio, 0.72; 95% confidence interval 0.56 to 0.93, p = 0.012) and very high dose statin use (odds ratio, 0.64; 95% confidence interval 0.43 to 0.92, p = 0.002). Obesity showed an inverse relation with the occurrence of gastro-intestinal upset (odds ratio, 0.65; 95% confidence interval 0.48 to 0.89, p = 0.007). Myalgia was more common with rosuvastatin use and less common with simvastatin use. Lower odds for intolerance due to myalgia were observed in patients using CYP3A4 isoenzyme substrates as compared to non-CYP3A4 isoenzyme substrate statins (1.0% versus 2.9% respectively, odds ratio 0.34; 92% confidence interval 0.20 to 0.57, p value < 0.001) Conclusions. Intolerance for low-dose colchicine in patients with coronary disease was seen in approximately one of every eleven patients and encompassed gastro- intestinal upset, myalgia or fatigue. Female sex was associated with increased odds for intolerance, while obesity and high-dose statin use were associated with lower odds for intolerance.