Aernoud Fiolet

84 Chapter 3 Methodologic challenges lead to limited evidence on the interaction of longterm colchicine administration, statins and the occurrence of myopathy. 60,61 The profile of interaction is based on pharmacokinetic parameters and anecdotal case reports. 62,63 There is a bidirectional interaction between colchicine and statins, giving rise to increased concentrations of both compounds and associated side effects. 60,62,64 An increased risk of developing myopathy or myotoxicity exists in patients using statins and colchicine but is observed only in patients with mild or severe renal impairment. 65,66 The perspective of the risk and clinical relevance of myopathy in patients taking statins and colchicine will become clear when results of ongoing clinical trials are available. Currently, co-administration of low-dose colchicine and statins is considered reasonable, taking into account monitoring for muscle-related toxicity. 64 Imidazole antifungal drugs, protease inhibitors, and cyclosporine are cytochrome P450 3A4 and P-glycoprotein inhibitors as well, and they might cause elevated colchicine levels. This scenario has only been described for ketoconazole in a small number of case reports. 46,62,67,68 CONCLUSIONS Contemporary evidence indicates that the slowly progressive nature of atherosclerosis might best be managed by addressing the 3 main pillars of the disease: controlling dyslipidemia, hemostasis, and the inflammatory response. Cholesterol crystal–induced inflammation represents an interplay of interleukins, neutrophils, and complement. Colchicine has the ability to dampen multiple cellular pathways, and there are some clinical trials indicating a protective effect in stable coronary artery disease. Furthermore, the drug seems to be safe in long- term use in various cardiovascular conditions. The body of evidence regarding its efficacy in stable and acute phases of coronary artery disease is expected to be broadened during the upcoming years. This information will certainly contribute to determining whether this well-known, low-cost drug may once be of additive value in controlling inflammation in coronary artery disease, a hallmark biologic feature of atherosclerosis.