Aernoud Fiolet

176 Chapter 7 Atherosclerosis is characterized by inflammation in response tomodified lipids and other pro-inflammatory stimuli. 7–9 Colchicine has broad anti-inflammatory effects by inhibiting microtubule formation, mitosis, leucocyte motility, and cytokine release from a range of inflammatory cells 10–12 (Graphical abstract). Recent trials have demonstrated that colchicine reduces major adverse cardiovascular events (MACE) in patients with coronary disease. 13,14 These trials involved patients with either acute or chronic coronary disease and were not designed to assess the effect on individual endpoints such as myocardial infarction, stroke, or cardiovascular death.We performed a systematic review and meta-analysis of randomized clinical trials to obtain estimates of the overall effect of colchicine onMACE and individual components of MACE in patients with coronary disease. METHODS Protocol We performed this meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. 15,16 We developed a protocol which was submitted to PROSPERO on 17 July 2020 and registered with the number CRD42020183283. Search strategy and selection criteria A search of all randomized trials comparing colchicine to placebo or no colchicine in patients with clinical atherosclerotic disease published up to 1 September 2020 was performed by two independent reviewers (T.S.J.O. and A.T.L.F.) on PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov without language or publication date restrictions. The key search terms used were ‘atherosclerosis’, ‘myocardial ischemia’, ‘brain ischemia’, ‘peripheral artery disease’, and ‘colchicine’, including their subheadings and synonyms. Sensitivity-maximizing filters as recommended by the Cochrane Collaboration were applied to identify randomized controlled trials in Embase and PubMed. 17,18 The complete search algorithm is presented in the Supplementary material,Appendix. Studies were eligible if they compared the efficacy of long-term colchicine treatment (≥3months) with standard treatment with or without placebo in a patient population with established atherosclerosis. Studies were excluded if they lacked reporting of anycardiovascular endpoint, such asmyocardial infarction, stroke, coronary revascularization, or cardiovascular death. Discrepancies over eligibility were resolved through consensus with a third reviewer (J.H.C.).