Aernoud Fiolet

108 Chapter 4 cohort includes a broad range of patients seen in general cardiology practice, and unlike CANTOS, participants were not selected on the basis of a predefined level of hs-CRP or other clinical markers of CV risk. Development of diabetes mellitus and atrial fibrillation are common inflammatory driven conditions in patients with coronary artery disease. Colchicine has shown to reduce post-operative atrial fibrillation and might improve metabolic status in diabetes. 45,46 Whether colchicine has any effect in modulating the involved inflammatory pathways in such a manner that it might reduce their incidence has thus been added as a part of the exploratory tertiary outcomes. Aside early intolerance to colchicine that may occur in up to 10% of people, long term use of low-dose (0.5 mg daily) colchicine is well tolerated, safe, and already approved by the United States Food and Drug Administration for the long-term secondary prevention of gout and FMF. 47 Of importance in patients with CV disease, colchicine 0.5 mg daily does not affect lipid levels, bleeding time or blood pressure, is not pro-arrhythmic, and has never been reported to cause any clinically important drug interaction when prescribed with the full range of medications commonly used in the treatment of CV disease. Of the potential drug interactions between colchicine and drugs eliminated via hepatic cytochrome (CYP) 3A4, just the interaction with the macrolide clarithromycin appears clinically important and only when colchicine is administered at doses >1 mg/day. 48 In addition, colchicine does not directly affect renal or liver function and can be used safely at low-dose in patients with renal and liver disease. 49,50 In patients with FMF, long-term colchicine can reverse renal amyloid and it is also known to be beneficial in some forms of cirrhosis. Although colchicine has no direct myotoxic effects, isolated case reports of myotoxicity have been reported with its use at doses >1 mg daily in patients with moderate renal impairment soon after the commencement of each class of statin. 51-53 In the current study, patients with moderate renal impairment were excluded and statin dosing left to the discretion of the treating physician. Significant bone marrow toxicity and death related to colchicine has only occurred in the setting of intentional overdose or co-administration with clarithromycin. 48 Currently three other phase 3 randomized trials are examining the effects of colchicine in patients following an acute coronary syndrome and one in cerebrovascular disease (Table IV). 54 The Colchicine Cardiovascular Outcomes